Formoterol fumarate is a long-acting beta2-adrenergic agonist (LABA) used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). It works by relaxing the muscles in the airways, making it easier to breathe. Formoterol fumarate is typically administered as an inhaled powder or solution. The synthesis of formoterol fumarate involves several steps, including the coupling of a chiral amine with a substituted phenethyl alcohol followed by esterification with fumaric acid. Formoterol fumarate is a potent bronchodilator and has a long duration of action, making it an effective treatment option for patients with asthma and COPD. It is studied extensively to understand its efficacy and safety profile, as well as to develop new formulations and delivery methods. Formoterol fumarate is a valuable therapeutic agent for individuals with respiratory conditions, improving their quality of life by reducing symptoms and improving lung function.'
N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide : A phenylethanoloamine having 4-hydroxy and 3-formamido substituents on the phenyl ring and an N-(4-methoxyphenyl)propan-2-yl substituent. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 3410 |
| CHEMBL ID | 1256786 |
| CHEBI ID | 63082 |
| CHEBI ID | 5147 |
| SCHEMBL ID | 349579 |
| SCHEMBL ID | 15856256 |
| MeSH ID | M0311929 |
| Synonym |
|---|
| AC-459 |
| cgp-25827a |
| bd-40a |
| formoterolum [inn-latin] |
| NCGC00181126-01 |
| C07805 |
| DB00983 |
| 2'-hydroxy-5'-(1-hydroxy-2-((p-methoxy-alpha-methylphenethyl)amino)ethyl)formanilide |
| 2'-hydroxy-5'-{1-hydroxy-2-[(p-methoxy-alpha-methylphenethyl)amino]ethyl}formanilide |
| n-[2-hydroxy-5-(1-hydroxy-2-{[2-(4-methoxyphenyl)-1-methylethyl]amino}ethyl)phenyl]formamide |
| L000259 |
| formoterol (inn) |
| oxis (tn) |
| D07990 |
| n-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl]formamide |
| n-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide |
| cas_73573-87-2 |
| bdbm86453 |
| nsc_3083544 |
| AKOS015961179 |
| CHEMBL1256786 |
| CHEBI:63082 , |
| gtpl3465 |
| oxeze/oxis |
| SCHEMBL349579 |
| BPZSYCZIITTYBL-UHFFFAOYSA-N |
| SCHEMBL15856256 |
| STL450992 |
| 126587-85-7 |
| AS-14186 |
| Q637247 |
| 128954-45-0 |
| SB17482 |
| AT22502 |
| n-[2-hydroxy-5-[(1rs)-1-hydroxy-2-[[(1rs)-2(4methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl] formamide |
| formoterol-d6 (major) |
| n-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formamide |
| DTXSID20860603 |
| EN300-7480042 |
| formamide, n-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]-, [s-(r*,s*)]- |
| formamide, n-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]-, [r-(r*,s*)]- |
| n-(2-hydroxy-5-((1rs)-1-hydroxy-2-(((2rs)-1-(4-methoxyphenyl)propan-2-yl)amino)ethyl)phenyl)formamide |
| (+/-)-2'-hydroxy-5'- |
| formoterolum (inn-latin) |
| 3-formylamino-4-hydroxy-alpha- |
| chebi:5147 |
| r03ac13 |
| dtxcid4065311 |
| rel-n- |
| Excerpt | Relevance | Reference |
|---|---|---|
| " An improved method for measuring the absorbed fraction of analogues dosed to rats, which considers the glucuronidated fraction is presented." | ( The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. Barrett, VJ; Bevan, NJ; Butchers, PR; Conroy, R; Emmons, A; Ford, AJ; Jeulin, S; Looker, BE; Lunniss, GE; Morrison, VS; Mutch, PJ; Perciaccante, R; Procopiou, PA; Ruston, M; Smith, CE; Somers, G, 2011) | 0.37 |
| " Through this process a novel, high potency, full β(2)-agonist with high selectivity and long duration capable of being dosed once daily has been discovered." | ( Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. Alcaraz, L; Bailey, A; Cadogan, E; Christie, J; Connolly, S; Cook, AR; Fisher, AJ; Hill, S; Humphries, A; Ingall, AH; Kane, Z; Paine, S; Pairaudeau, G; Stocks, MJ; Young, A, 2011) | 0.37 |
| Class | Description |
|---|---|
| phenols | Organic aromatic compounds having one or more hydroxy groups attached to a benzene or other arene ring. |
| formamides | Amides with the general formula R(1)R(2)NCHO (R(1) and R(2) can be H). |
| secondary amino compound | A compound formally derived from ammonia by replacing two hydrogen atoms by organyl groups. |
| secondary alcohol | A secondary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has two other carbon atoms attached to it. |
| phenylethanolamines | An ethanolamine compound having a phenyl (substituted or unsubstituted) group on the carbon bearing the hydroxy substituent. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| GLS protein | Homo sapiens (human) | Potency | 25.1189 | 0.3548 | 7.9355 | 39.8107 | AID624170 |
| peripheral myelin protein 22 | Rattus norvegicus (Norway rat) | Potency | 0.1018 | 0.0056 | 12.3677 | 36.1254 | AID624032 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Beta-2 adrenergic receptor | Homo sapiens (human) | Ki | 0.0191 | 0.0000 | 0.6635 | 9.5499 | AID1152885; AID1185817; AID1224049; AID1298705; AID238673; AID481516; AID501435; AID578408 |
| Beta-1 adrenergic receptor | Homo sapiens (human) | IC50 (µMol) | 0.6310 | 0.0002 | 1.4681 | 9.0000 | AID609376; AID643244 |
| Beta-1 adrenergic receptor | Homo sapiens (human) | Ki | 0.8764 | 0.0001 | 1.3391 | 9.9840 | AID1152886; AID1185818; AID501436 |
| D(2) dopamine receptor | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 0.7472 | 8.0000 | AID609372 |
| D(2) dopamine receptor | Homo sapiens (human) | Ki | 13.0000 | 0.0000 | 0.6518 | 10.0000 | AID1298708 |
| D(3) dopamine receptor | Homo sapiens (human) | Ki | 1.6260 | 0.0000 | 0.6020 | 10.0000 | AID1185819 |
| Beta-2 adrenergic receptor | Cavia porcellus (domestic guinea pig) | IC50 (µMol) | 0.0004 | 0.0004 | 0.1680 | 0.9772 | AID1185820 |
| Beta-2 adrenergic receptor | Cavia porcellus (domestic guinea pig) | Ki | 0.6833 | 0.0004 | 0.5902 | 2.5119 | AID1152885; AID1152886; AID481516 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Beta-1 adrenergic receptor | Cavia porcellus (domestic guinea pig) | EC50 (µMol) | 0.0005 | 0.0003 | 0.0116 | 0.0398 | AID414892 |
| Beta-2 adrenergic receptor | Homo sapiens (human) | EC50 (µMol) | 0.0014 | 0.0000 | 0.3111 | 10.0000 | AID1137772; AID1152884; AID1152893; AID1224052; AID1224054; AID414892; AID438908; AID447902; AID481517; AID501437; AID578409; AID606103; AID609373; AID611239; AID643219 |
| Beta-2 adrenergic receptor | Homo sapiens (human) | Kd | 0.0025 | 0.0000 | 0.6288 | 8.9130 | AID770362 |
| Beta-1 adrenergic receptor | Homo sapiens (human) | EC50 (µMol) | 0.0461 | 0.0001 | 0.4914 | 6.0000 | AID1152890; AID1224051; AID414891; AID438906; AID447901; AID611237 |
| Beta-3 adrenergic receptor | Homo sapiens (human) | EC50 (µMol) | 0.0251 | 0.0001 | 0.4553 | 10.0000 | AID1152891; AID1224053; AID414894; AID611236 |
| Histamine H2 receptor | Cavia porcellus (domestic guinea pig) | EC50 (µMol) | 0.0005 | 0.0003 | 0.5719 | 1.2023 | AID414892 |
| Beta-2 adrenergic receptor | Cavia porcellus (domestic guinea pig) | EC50 (µMol) | 0.0014 | 0.0002 | 0.8843 | 8.2000 | AID1152893; AID481517; AID611234 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID414919 | Agonist activity at beta-1 adrenergic receptor in guinea pig trachea assessed as ratio of EC50 for inhibition of electrical stimulation-induced contraction after 1 hr of compound washout to EC50 at equilibrium before washout | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID510458 | Bronchodilatory activity in itr dosed Beagle dog assessed as inhibition of acetylcholine-induced bronchoconstriction administered 5 doses of compound at cumulative 1 hr intervals | 2010 | Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18 | Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. |
| AID238673 | Binding affinity for human beta-2 adrenergic receptor | 2004 | Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18 | Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity. |
| AID1152891 | Agonist activity at human recombinant beta3 receptor assessed as cAMP accumulation by radioimmunoassay and cell based assay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID438906 | Agonist activity at human adrenergic beta 1 expressed in CHO-K1 cells assessed as intracellular cAMP accumulation | 2009 | Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23 | Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. |
| AID1458047 | Binding affinity to POPC liposome membrane at compound to POPC molar ratio of 1:10 after 300 milliseconds by NOESY 1H NMR analysis | 2017 | Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16 | Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR. |
| AID481525 | Inhibition of serotonin-induced bronchoconstriction in guinea pig assessed as intrinsic duration of bronchodilatory activity at ED80 | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID414892 | Agonist activity at human cloned beta2 adrenergic receptor expressed in CHO cells assessed as induction of intracellular cAMP accumulation by beta-galactosidase based whole cell assay | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID625292 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID447901 | Agonist activity at human beta-1 adrenoceptor expressed in CHOK1 cell assessed as increase of intracellular cAMP level | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID236903 | Partition coefficient (logD) | 2004 | Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18 | Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity. |
| AID625291 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID1137808 | Toxicity in iv dosed guinea pig assessed as change in plasma potassium level up to 60 mins | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID1185821 | Agonist activity at adrenergic beta2 receptor in electrically-stimulated Dunkin-Hartley guinea pig tracheal strip assessed as time to maximal effect at IC50 | 2014 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 24, Issue:17 | The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. |
| AID1185817 | Displacement of [125I]iodo-(+/-)-cyanopindolol from human adrenergic beta2 receptor expressed in CHO cells after 3 hrs by radio-ligand binding assay | 2014 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 24, Issue:17 | The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. |
| AID1224054 | Agonist activity at human beta2 adrenergic receptor in human BEAS-2B cells by cAMP accumulation assay | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID609371 | Selectivity ratio of IC50 for dopamine 2 receptor over EC50 for human adrenergic beta2 receptor | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID643219 | Agonist activity at human beta2 adrenoceptor expressed in H292 cells assessed as increase in cAMP accumulation after 60 mins by spectrophotometry | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID501437 | Agonist activity at beta 2 in human A431 cells adrenoceptor assessed as cAMP accumulation | 2010 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 20, Issue:17 | A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of beta2-adrenoceptor agonists as inhaled long-acting bronchodilators. |
| AID1137785 | Agonist activity at beta-2 adrenergic receptor in guinea pig tracheal rings assessed as time required to reach 90% of final relaxation of methacholine-constricted tracheal rings | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID524796 | Antiplasmodial activity against Plasmodium falciparum W2 after 72 hrs by SYBR green assay | 2009 | Nature chemical biology, Oct, Volume: 5, Issue:10 | Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum. |
| AID510462 | Therapeutic index, ratio of dose inducing cardiovascular side effects to ED50 for inhibition of acetylcholine-induced bronchoconstriction in itr dosed Beagle dog | 2010 | Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18 | Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. |
| AID643246 | Drug metabolism in rat hepatocytes | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID609377 | Selectivity ratio of IC50 for adrenergic beta1 receptor over EC50 for human adrenergic beta2 receptor | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID447904 | Agonist activity at human beta-1 adrenoceptor expressed in CHOK1 cell assessed as increase of intracellular cAMP level relative to isoprenaline | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID510459 | Bronchodilatory activity in itr dosed Beagle dog assessed as duration of blockade of acetylcholine-induced bronchoconstriction at ED50 administered as single dose prior to acetylcholine challenge | 2010 | Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18 | Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. |
| AID414893 | Intrinsic activity at human cloned beta2 adrenergic receptor expressed in CHO cells assessed as induction of intracellular cAMP accumulation by beta-galactosidase based whole cell assay relative to isoprenaline | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID643244 | Binding affinity to beta1 adrenoceptor | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID611239 | Agonist activity at human adrenergic beta2 receptor expressed in CHO cells assessed as cAMP accumulation | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID609382 | Agonist activity at adrenergic beta1 receptor | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID1224050 | Selectivity ratio of Ki for human beta1 adrenergic receptor to Ki for human beta2 adrenergic receptor | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID1152884 | Agonist activity at human recombinant beta2 receptor assessed as cAMP accumulation by radioimmunoassay and cell based assay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID438908 | Agonist activity at human adrenergic beta 2 expressed in CHO-K1 cells assessed as intracellular cAMP accumulation | 2009 | Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23 | Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. |
| AID611145 | Agonist activity at adrenergic beta2 receptor in guinea pig trachea assessed as duration of action expressed as rightward shift in the agonist concentration-effect curve following 3 hrs of washout | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID1458045 | Binding affinity to POPC liposome membrane assessed as 31P chemical shift anisotropy at compound to POPC molar ratio of 1:10 by NMR analysis (Rvb = 28.9 ppm) | 2017 | Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16 | Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR. |
| AID611238 | Intrinsic activity at human adrenergic beta2 receptor expressed in CHO cells assessed as cyclic AMP accumulation relative to isoprenaline | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID1298712 | Selectivity index, ratio of Ki for human D2S receptor to Ki for human beta2 receptor | 2016 | Bioorganic & medicinal chemistry, 06-15, Volume: 24, Issue:12 | Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists. |
| AID447908 | Toxicity in guinea pig assessed as increase in heart rate at 10 ug/kg, intratracheally after 90 mins | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID481520 | Agonist activity at beta2 adrenergic receptor in guinea pig tracheal strip assessed as time required to reach maximal inhibition of electrically-induced bronchoconstriction | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID1152890 | Agonist activity at human recombinant beta1 receptor assessed as cAMP accumulation by radioimmunoassay and cell based assay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID414918 | Agonist activity at beta-1 adrenergic receptor in guinea pig trachea assessed as onset time for 50% inhibition of electrical stimulation-induced muscle contraction | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID625281 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID447910 | Selectivity ratio, EC50 for human beta-1 adrenoceptor to EC50 for human beta2 adrenoceptor | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID481519 | Agonist activity at beta2 adrenergic receptor in guinea pig tracheal strip assessed as inhibition of electrically-induced bronchocontractile response after 30 mins | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID1137783 | Intrinsic activity at beta-2 adrenergic receptor in guinea pig tracheal rings | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID1185820 | Agonist activity at adrenergic beta2 receptor in electrically-stimulated Dunkin-Hartley guinea pig tracheal strip assessed as inhibition of contraction | 2014 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 24, Issue:17 | The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. |
| AID447912 | Bronchoprotective activity in intratracheally dosed guinea pig assessed as inhibition of acetylcholine-induced increase in pulmonary resistance at 0.3 ug/kg, intratracheally after 30 mins | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID609380 | Bronchodilatory activity in intratracheally dosed guinea pig assessed as inhibition of histamine-induced bronchoconstriction | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID481521 | Agonist activity at beta2 adrenergic receptor in guinea pig tracheal strip assessed as duration of maximal inhibitory action against electrically-induced bronchoconstriction | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID1137807 | Bronchoprotective activity in guinea pig assessed as inhibition of histamine-induced bronchoconstriction at ED80 administered intratracheally after 4 to 24 hrs relative to control | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID770362 | Binding affinity to beta-2 adrenergic receptor (unknown origin) at 1 to 10000 nM | 2013 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 23, Issue:19 | β2-Adrenoceptor agonists in the regulation of mitochondrial biogenesis. |
| AID625288 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID415158 | Agonist activity at beta-1 adrenergic receptor in guinea pig trachea assessed as ratio of EC50 for inhibition of electrical stimulation-induced contraction after 3 hrs of compound washout to EC50 at equilibrium before washout | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID1137784 | Agonist activity at beta-2 adrenergic receptor in human bronchial rings assessed as time required to reach 90% of final relaxation of carbachol-constricted bronchial rings | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID501435 | Displacement of [3H]CGP12177 from human beta2 adrenoceptor | 2010 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 20, Issue:17 | A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of beta2-adrenoceptor agonists as inhaled long-acting bronchodilators. |
| AID447907 | Bronchoprotective activity in guinea pig assessed as inhibition of acetylcholine-induced increase in pulmonary resistance at 1 ug/kg, intratracheally after 5 hrs | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID1152883 | Selectivity ratio EC50 for human beta2 receptor to EC50 for human beta1 receptor | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID248534 | Concentration required to inhibit electrically induced contraction of superfused guinea-pig trachea was determined | 2004 | Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18 | Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity. |
| AID609372 | Binding affinity to dopamine 2 receptor | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID1185822 | Agonist activity at adrenergic beta2 receptor in electrically-stimulated Dunkin-Hartley guinea pig tracheal strip assessed as time for response to fall to 50% of maximal response during washout phase at IC50 | 2014 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 24, Issue:17 | The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. |
| AID578409 | Agonist activity at human beta2-adrenoceptor expressed in HEK cells assessed as increase of cAMP level after 10 mins by radioimmunoassay | 2011 | Bioorganic & medicinal chemistry letters, Mar-01, Volume: 21, Issue:5 | Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules. |
| AID481523 | Intrinsic clearance in rat liver microsomes assessed per mg of protein at 1 uM after 10 to 30 mins by LC/MS analysis in presence of NADPH | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID1185819 | Displacement of [125I]7-HO-PIPAT from human D3R expressed in HEK cells | 2014 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 24, Issue:17 | The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. |
| AID1152887 | Selectivity ratio Ki for beta2 receptor (unknown origin) to Ki for beta1 receptor (unknown origin) | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID1137773 | Intrinsic activity at human beta-2 adrenergic receptor expressed in human H292 cells relative to formoterol | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID625289 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID611236 | Agonist activity at human adrenergic beta3 receptor expressed in CHO cells assessed as cAMP accumulation | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID625286 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID625287 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID1224049 | Displacement of [3H]dihydroalprenolol from human beta2 adrenergic receptor expressing cell membrane by competition binding assay | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID611147 | Agonist activity at adrenergic beta2 receptor in guinea pig trachea assessed as time taken for EC50 concentration to achieve 50% maximum relaxant effect | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID1137772 | Agonist activity at human beta-2 adrenergic receptor expressed in human H292 cells assessed as accumulation of intracellular cAMP after 1 hr by AlphaScreen assay | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID251147 | Duration action in guinea pig | 2004 | Bioorganic & medicinal chemistry letters, Sep-20, Volume: 14, Issue:18 | Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity. |
| AID501438 | Intrinsic activity at beta 2 in human A431 cells adrenoceptor assessed as cAMP accumulation | 2010 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 20, Issue:17 | A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of beta2-adrenoceptor agonists as inhaled long-acting bronchodilators. |
| AID578408 | Displacement of [3H]-dihydroalprenolol from human beta2-adrenoceptor expressed in HEK cells after 4 hrs | 2011 | Bioorganic & medicinal chemistry letters, Mar-01, Volume: 21, Issue:5 | Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules. |
| AID625290 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID1152886 | Displacement of [3H]dihydroalprenolol from beta1 receptor (unknown origin) by liquid scintillation counting and cell based assay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID524792 | Antiplasmodial activity against Plasmodium falciparum D10 after 72 hrs by SYBR green assay | 2009 | Nature chemical biology, Oct, Volume: 5, Issue:10 | Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum. |
| AID1152885 | Displacement of [3H]dihydroalprenolol from beta2 receptor (unknown origin) by liquid scintillation counting and cell based assay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID609376 | Binding affinity to adrenergic beta1 receptor | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID643243 | 1-Octanol-aqueous buffer distribution coefficient, log D at pH 7.4 by LC/MS analysis | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID438907 | Agonist activity at human adrenergic beta 1 expressed in CHO-K1 cells assessed as intracellular cAMP accumulation relative to isoprenaline | 2009 | Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23 | Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. |
| AID611146 | Agonist activity at adrenergic beta2 receptor in guinea pig trachea assessed as duration of action expressed as rightward shift in the agonist concentration-effect curve following 1 hrs of washout | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID414894 | Agonist activity at human cloned beta3 adrenergic receptor expressed in CHO cells assessed as induction of intracellular cAMP accumulation by beta-galactosidase based whole cell assay | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID1152888 | Agonist activity at beta2 receptor in guinea pig trachea assessed as fast onset of inhibition of electrically stimulated contraction | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID1152892 | Selectivity ratio EC50 for human beta2 receptor to EC50 for human beta3 receptor | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID438909 | Agonist activity at human adrenergic beta 2 expressed in CHO-K1 cells assessed as intracellular cAMP accumulation relative to isoprenaline | 2009 | Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23 | Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. |
| AID481516 | Displacement of [125I]cyanopindolol from human recombinant beta2 adrenergic receptor expressed in CHO cells by filtration assay | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID625285 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID447903 | Agonist activity at human beta2 adrenoceptor expressed in CHOK1 cell assessed as increase of intracellular cAMP level relative to isoprenaline | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID1137786 | Agonist activity at beta-2 adrenergic receptor in guinea pig tracheal rings assessed as relaxation of methacholine-constricted tracheal rings | 2014 | ACS medicinal chemistry letters, Apr-10, Volume: 5, Issue:4 | Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. |
| AID1152894 | Intrinsic activity at human beta2 receptor in BEAS-2B cells assessed as cAMP accumulation by radioimmunoassay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID414917 | Selectivity assessed as difference in pEC50 for human cloned beta2 adrenergic receptor and pEC50 for human cloned beta3 adrenergic receptor | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID1185818 | Displacement of [125I]iodo-(+/-)-cyanopindolol from human adrenergic beta1 receptor expressed in CHO cells after 3 hrs by radio-ligand binding assay | 2014 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 24, Issue:17 | The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist. |
| AID510460 | Bronchodilatory activity in itr dosed Beagle dog assessed as duration of blockade of acetylcholine-induced bronchoconstriction at 10 times ED50 administered as single dose prior to acetylcholine challenge | 2010 | Journal of medicinal chemistry, Sep-23, Volume: 53, Issue:18 | Inhalation by design: novel ultra-long-acting β(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. |
| AID770364 | Induction of Mitochondrial biogenesis in rabbit RPT cells at 10 to 3000 nM after 24 hrs by FCCP-OCR assay relative to control | 2013 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 23, Issue:19 | β2-Adrenoceptor agonists in the regulation of mitochondrial biogenesis. |
| AID1298705 | Displacement of [3H]CGP12177 from human beta2 receptor expressed in CHO cells | 2016 | Bioorganic & medicinal chemistry, 06-15, Volume: 24, Issue:12 | Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists. |
| AID447902 | Agonist activity at human beta2 adrenoceptor expressed in CHOK1 cell assessed as increase of intracellular cAMP level | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID625284 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID1224055 | Intrinsic agonist activity at human beta2 adrenergic receptor in human BEAS-2B cells by cAMP accumulation assay relative to isoproterenol | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID521220 | Inhibition of neurosphere proliferation of mouse neural precursor cells by MTT assay | 2007 | Nature chemical biology, May, Volume: 3, Issue:5 | Chemical genetics reveals a complex functional ground state of neural stem cells. |
| AID611235 | Metabolic stability in human liver microsomes with 125 pmol/mL P450 assessed as compound turnover ratio at 5 uM after 30 mins by LC-MS method relative to verapamil | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID481512 | Chromatographic hydrophobicity index at 2 mg/ml at pH 7.4 by rapid gradient HPLC analysis | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID524795 | Antiplasmodial activity against Plasmodium falciparum HB3 after 72 hrs by SYBR green assay | 2009 | Nature chemical biology, Oct, Volume: 5, Issue:10 | Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum. |
| AID438910 | Selectivity, ratio of EC50 for human adrenergic beta 1 to EC50 for human adrenergic beta 2 | 2009 | Bioorganic & medicinal chemistry letters, Dec-01, Volume: 19, Issue:23 | Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. |
| AID1458062 | Binding affinity to POPC liposome membrane assessed as cross-relaxation rate of H proton with C-3/C-2 region of lipid at compound to POPC molar ratio of 1:10 by NOESY 1H NMR analysis | 2017 | Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16 | Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR. |
| AID1224053 | Agonist activity at human beta3 adrenergic receptor expressed in cells by cAMP accumulation assay | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID643245 | Selectivity ratio of pIC50 for beta1 adrenoceptor to pEC50 for human beta2 adrenoceptor | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID1458059 | Lipophilicity of the compound assessed as capacity factor (CHI IAM7.4) at pH 7.4 by chromatographic analysis | 2017 | Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16 | Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR. |
| AID414916 | Selectivity assessed as difference in pEC50 for human cloned beta2 adrenergic receptor and pEC50 for human cloned beta-1 adrenergic receptor | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID501436 | Displacement of [3H]CGP12177 from human beta-1 adrenoceptor | 2010 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 20, Issue:17 | A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of beta2-adrenoceptor agonists as inhaled long-acting bronchodilators. |
| AID606106 | Bronchodilatory activity against histamine-induced bronchoconstriction in guinea pig at ED80 intratracheally administered 2 hrs before challenge measured up to 12 hrs | 2011 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 21, Issue:13 | Design driven HtL: The discovery and synthesis of new high efficacy β₂-agonists. |
| AID625282 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID609378 | Half life in iv dosed rat plasma | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID609375 | Octanol-phosphate buffer distribution coefficient, log D of the compound at pH 7.4 by LC/MS analysis | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID643231 | Terminal half life in iv dosed rat | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID447913 | Bronchoprotective activity in intratracheally dosed guinea pig assessed as inhibition of acetylcholine-induced increase in pulmonary resistance at 1 ug/kg, intratracheally after 150 mins | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID606103 | Agonist activity at human adrenergic beta2 receptor expressed in H292 cells assessed as intracellular cAMP accumulation after 1 hr | 2011 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 21, Issue:13 | Design driven HtL: The discovery and synthesis of new high efficacy β₂-agonists. |
| AID524790 | Antiplasmodial activity against Plasmodium falciparum 3D7 after 72 hrs by SYBR green assay | 2009 | Nature chemical biology, Oct, Volume: 5, Issue:10 | Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum. |
| AID414895 | Agonist activity at beta-1 adrenergic receptor in guinea pig trachea assessed as inhibition of electrical stimulation-induced muscle contraction | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID625280 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID447911 | Bronchoprotective activity in intratracheally dosed guinea pig assessed as inhibition of acetylcholine-induced increase in pulmonary resistance after 5 hrs | 2009 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 19, Issue:17 | Studies towards topical selective beta2-adrenoceptor agonists with a long duration of action. |
| AID1152893 | Agonist activity at human beta2 receptor in BEAS-2B cells assessed as cAMP accumulation by radioimmunoassay | 2014 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 24, Issue:12 | Multivalent design of long-acting β(2)-adrenoceptor agonists incorporating biarylamines. |
| AID414891 | Agonist activity at human cloned beta-1 adrenergic receptor expressed in CHO cells assessed as induction of intracellular cAMP accumulation by beta-galactosidase based whole cell assay | 2009 | Journal of medicinal chemistry, Apr-23, Volume: 52, Issue:8 | Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating arylsulfonamide groups. |
| AID611237 | Agonist activity at human adrenergic beta1 receptor expressed in CHO cells assessed as cAMP accumulation | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID1298708 | Displacement of [3H]spiperone from human D2S receptor expressed in CHO cells | 2016 | Bioorganic & medicinal chemistry, 06-15, Volume: 24, Issue:12 | Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists. |
| AID643235 | Bronchoprotective activity in it dosed guinea pig assessed as inhibition of histamine-induced constriction | 2012 | Bioorganic & medicinal chemistry letters, Jan-01, Volume: 22, Issue:1 | From libraries to candidate: the discovery of new ultra long-acting dibasic β₂-adrenoceptor agonists. |
| AID1224052 | Agonist activity at human beta2 adrenergic receptor expressed in cells by cAMP accumulation assay | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID1224051 | Agonist activity at human beta1 adrenergic receptor expressed in cells by cAMP accumulation assay | 2014 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 24, Issue:13 | Discovery of TD-4306, a long-acting β2-agonist for the treatment of asthma and COPD. |
| AID625283 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID1458057 | n-octanol/PBS/sodium carbonate partition coefficient, log P of the compound after 4 hrs | 2017 | Journal of medicinal chemistry, 08-24, Volume: 60, Issue:16 | Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR. |
| AID481524 | Intrinsic clearance in rat liver microsomes assessed per mg of protein at 1 uM after 10 to 30 mins by LC/MS analysis in presence of UDP-glucuronic acid | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID481517 | Agonist activity at human beta2 adrenergic receptor assessed as increase in cAMP level by whole cell assay | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID625279 | Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia | 2011 | PLoS computational biology, Dec, Volume: 7, Issue:12 | Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps). |
| AID609373 | Agonist activity at human adrenergic beta2 receptor expressed in H292 cells assessed as stimulation of cAMP accumulation after 60 mins | 2011 | Bioorganic & medicinal chemistry letters, Aug-01, Volume: 21, Issue:15 | Design-driven LO: the discovery of new ultra long acting dibasic β2-adrenoceptor agonists. |
| AID611234 | Agonist activity at adrenergic beta2 receptor in guinea pig trachea assessed as inhibition of electrically-stimulated contraction | 2011 | Bioorganic & medicinal chemistry, Jul-15, Volume: 19, Issue:14 | The discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating hydantoin or uracil rings. |
| AID481513 | Binding affinity to human serum albumin by UV/HPLC analysis | 2010 | Journal of medicinal chemistry, May-13, Volume: 53, Issue:9 | The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonist. |
| AID504749 | qHTS profiling for inhibitors of Plasmodium falciparum proliferation | 2011 | Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043 | Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. |
| AID1346250 | Human beta2-adrenoceptor (Adrenoceptors) | 2010 | British journal of pharmacology, Jul, Volume: 160, Issue:5 | The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 6 (25.00) | 29.6817 |
| 2010's | 18 (75.00) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.
| This Compound (80.37) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 24 (100.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| Evaluation and Treatment of Small Airways in COPD [NCT02526758] | Phase 4 | 90 participants (Anticipated) | Interventional | 2015-04-30 | Recruiting | ||
| Childhood Asthma and Return to School: the September Epidemic Exacerbation in Israel.A Controlled Trial of the Effectiveness of Preventive Treatment With Symbicort or Budicort Turbuhaler [NCT01179152] | 225 participants (Anticipated) | Interventional | 2010-09-30 | Recruiting | |||
| A Phase III, Randomized, Open-label, Non-inferiority Study Comparative of Formoterol/Fluticasone Eurofarma 12/250 µg, Foraseq® 12/400 µg and Fluticasone 500 µg in Asthma Patients [NCT01202084] | Phase 3 | 222 participants (Actual) | Interventional | 2012-01-31 | Completed | ||
| Multicenter, Double-Blind, Double-Dummy, Randomized, Active-Controlled, Parallel Group Long-Term Safety Study of 15 μg and 25 μg Arformoterol Tartrate Inhalation Solution BID in Subjects With Chronic Obstructive Pulmonary Disease [NCT00250679] | Phase 3 | 443 participants (Actual) | Interventional | 2005-10-31 | Completed | ||
| Double Blind, Double Dummy, Cross-over Study to Compare the Bronchodilator Effect of CHF1535 pMDI (Fixed Combination of Beclometasone 50 µg + Formoterol 6 µg) Versus Free Combination of Beclometasone Plus Formoterol pMDI in Asthmatic Children [NCT01584492] | Phase 2 | 59 participants (Actual) | Interventional | 2011-12-31 | Completed | ||
| Sub-Sensitivity to Long-Acting Bronchodilators (LABA) [NCT01117116] | 21 participants (Actual) | Interventional | 2010-03-31 | Completed | |||
| Phase 3, Multicenter, Randomized, Parallel-Group, Open-Label, Comparative Non-Inferiority Fixed-Dose Combination Formoterol 6 mcg/Fluticasone 125 mcg Versus Alenia® (Formoterol 6 mcg/Budesonide 200 mcg) in the Treatment of Moderate Asthma [NCT05735431] | Phase 3 | 132 participants (Anticipated) | Interventional | 2024-07-30 | Not yet recruiting | ||
| A Randomized, Parallel-Group, Open, Two-Period, Comparative Non-Inferiority Study of Eurofarma's Formoterol/Budesonide vs Alenia in the Treatment of Moderate to Severe Persistent Asthma With and Without Chronic Obstructive Pulmonary COPD [NCT04233190] | Phase 3 | 472 participants (Anticipated) | Interventional | 2023-04-19 | Recruiting | ||
| An Open, Randomised, Parallel Group Multi-centre, Methodology Study, Evaluating the Sensitivity of Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) in Detecting and Comparing Response to 8 Weeks Treatment With Budesonide/Formoterol Turbuhaler® (320/9 µ [NCT01257048] | Early Phase 1 | 34 participants (Actual) | Interventional | 2011-08-31 | Completed | ||
| A Phase I, Randomised, Two-Period, Single-Dose, Single-Centre, Crossover Gamma Scintigraphy Study to Assess the Pulmonary Deposition of Technetium-99m Radiolabelled Budesonide, Glycopyrronium and Formoterol Fumarate MDI, Following 3 s and 10 s Breath-Hold [NCT03740373] | Phase 1 | 10 participants (Actual) | Interventional | 2018-09-04 | Completed | ||
| In-vivo Deposition Measurement of Beclometasone and Formoterol After Inhalation of a Single Dose of the Combination BDP Plus Formoterol NEXT DPI in Healthy Volunteers, Asthmatic and COPD Patients. [NCT01176747] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2010-08-31 | Completed | ||
| Effect of High Dose Inhaled Budesonide and Fluticasone on Adrenal Function in Patients With Moderate to Severe COPD [NCT01186653] | Phase 4 | 22 participants (Actual) | Interventional | 2007-10-31 | Completed | ||
| A Randomized, 26-Week, Placebo-Controlled Efficacy and Safety Study With a 26-Week Long-Term Safety Extension, of High- and Medium-Dose Inhaled Mometasone Furoate/Formoterol Fixed-Dose Combination Formulation Compared With Formoterol and High-Dose Inhaled [NCT00383721] | Phase 3 | 1,196 participants (Actual) | Interventional | 2006-09-30 | Completed | ||
| Dose Response Evaluation of CHF 1535 HFA pMDI in Asthmatic Patients Using Lung Function, Adenosine Monophosphate Bronchial Challenge and Fractional Exhaled Nitric Oxide (FENO) [NCT01343745] | Phase 2 | 18 participants (Actual) | Interventional | 2008-02-29 | Completed | ||
| A 24-week, Double Blind, Double Dummy, Randomized, Multinational, Multicentre, 2-arm Parallel Group,Active Controlled Clinical Trial of Fixed Combination of Beclometasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrronium Bromide Administered Via p [NCT03197818] | Phase 3 | 990 participants (Actual) | Interventional | 2016-12-14 | Completed | ||
| Personalized Treatment Algorithms for Difficult-to-treat Asthma: Bench to Community [NCT04179461] | Phase 2 | 21 participants (Actual) | Interventional | 2018-03-16 | Completed | ||
| A Randomized, Double-blind, Placebo and Active-controlled, Incomplete Block Cross-over, Dose Ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 1531 pMDI (Formoterol Fumarate) in Asthmatic Subjects [NCT03086460] | Phase 2 | 67 participants (Actual) | Interventional | 2017-09-08 | Completed | ||
| An Exploratory, Double-blind, Placebo-controlled Study of the Effects of Dupilumab on Airway Inflammation of Adults With Persistent Asthma [NCT02573233] | Phase 2 | 42 participants (Actual) | Interventional | 2016-01-27 | Completed | ||
| A Randomised, Double-Blind, Double-Dummy, Multicentre, Parallel Group Study to Assess the Efficacy and Safety of Glycopyrronium/Formoterol Fumarate Fixed-dose Combination Relative to Umeclidinium/Vilanterol Fixed-dose Combination Over 24 Weeks in Patients [NCT03162055] | Phase 3 | 1,119 participants (Actual) | Interventional | 2017-05-25 | Completed | ||
| A Phase I, Randomized, Double-Blind, Parallel-Group, Study to Assess the Pharmacokinetics and Safety of Two Doses of PT010 and a Single Dose of PT003 in Healthy Chinese Adult Subjects Following A Single Administrations and After Chronic Administration for [NCT03075267] | Phase 1 | 96 participants (Actual) | Interventional | 2017-04-17 | Completed | ||
| Open Label, Prospective Study to Evaluate the Effect of Step-up From Non-extra Fine Inhaled Corticosteroids/Long Acting Beta2 Agonist (ICS/LABA) Dry Powder Inhaler (DPI) to Extra Fine Triple Therapy With CHF5993 DPI on Airway Geometry and Lung Ventilation [NCT04876677] | Phase 3 | 25 participants (Actual) | Interventional | 2021-05-25 | Completed | ||
| A Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Effect of 28 Day Treatment With Fostair® Pressurized Metered-dose Inhaler (pMDI) 200/12 on Biomarkers of Platelet Adhesion in Patients With Idiopathic Pulmonary Fibrosis [NCT02048644] | Phase 2 | 20 participants (Actual) | Interventional | 2014-03-31 | Completed | ||
| Open-label, Randomized, 3-way Cross-over, Placebo Controlled, Single Dose Clinical Pharmacology Study in COPD Patients After Inhalation of CHF 5993 pMDI Using the Standard Actuator With or Without AeroChamber Plus Flow-Vu VHC Spacer [NCT02119234] | Phase 1 | 36 participants (Actual) | Interventional | 2014-03-31 | Completed | ||
| Activation of Brown Adipose Tissue Thermogenesis in Humans Using Formoterol Fumarate, a Beta-2 Adrenergic Receptor Agonist [NCT05553184] | 12 participants (Actual) | Interventional | 2022-07-05 | Completed | |||
| A Randomized, 26-Week, Placebo-Controlled Efficacy and Safety Study With a 26-Week Long-Term Safety Extension, of High- and Medium-Dose Inhaled Mometasone Furoate/Formoterol Fixed-Dose Combination Formulation Compared With Formoterol and High-Dose Inhaled [NCT00383435] | Phase 3 | 1,055 participants (Actual) | Interventional | 2006-10-31 | Completed | ||
| A 12-Week Efficacy and Safety Study of Two Doses of Mometasone Furoate/Formoterol Combination Formulation Compared With Mometasone Furoate Monotherapy, in Persistent Asthmatics Previously Treated With High-Dose Inhaled Glucocorticosteroids [NCT00381485] | Phase 3 | 834 participants (Actual) | Interventional | 2006-07-01 | Completed | ||
| Study Title: A Single-dose, Open-label, Randomised, 2-way Crossover, Clinical Pharmacology Study of Four Inhalations of CHF 1535 100/6 NEXT DPI® (Fixed Combination of Beclomethasone Diproponate 100 µg Plus Formoterol Fumarate 6 µg) Versus the Same Dose of [NCT01349257] | Phase 2 | 24 participants (Actual) | Interventional | 2011-05-31 | Completed | ||
| A MULTICENTRE, RANDOMISED, DOUBLE-BLIND, ACTIVE-CONTROLLED, 3-WAY CROSS-OVER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF A FREE COMBINATION OF 3 DOSES OF CHF 5259 (GLYCOPYRROLATE) PLUS FOSTER® 100/6 µg (FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE PL [NCT02127866] | Phase 2 | 211 participants (Actual) | Interventional | 2014-04-30 | Completed | ||
| Gender-specific Role of the beta2-adrenergic Stimulation With Short- or Long-acting Selective Agonist in Relation to Muscle Remodelling, Function, Performance, and Anti-doping [NCT03565302] | 72 participants (Anticipated) | Interventional | 2018-06-25 | Recruiting | |||
| A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005, PT008, and Open-label Symbicort® Turbuhaler®, as an Active Control, on Lung Function Over a 24-Week Treatment Period in Subjects W [NCT02766608] | Phase 3 | 2,389 participants (Actual) | Interventional | 2016-05-31 | Completed | ||
| A Phase III, Randomized, Non-inferiority, Open-label, Comparative Study Between Foraseq® Inhalation Capsules, Eurofarma's Single Formoterol / Budesonide Inhalation Capsule and Single Alenia® Inhalation Capsule in Asthmatic Patients [NCT01167010] | Phase 3 | 552 participants (Anticipated) | Interventional | 2011-04-30 | Completed | ||
| A Multicenter, Multinational, Single-Dose, Open Label, Randomized, 2-Way Crossover, Clinical Pharmacology Study of CHF 1535 100/6 Next™ DPI (Fixed Combination of Beclomethasone Dipropionate 100 µg Plus Formoterol 6 µg) Versus the Free Combination of Licen [NCT01191424] | Phase 2 | 57 participants (Actual) | Interventional | 2010-10-31 | Completed | ||
| A Phase IV, 12-week, Randomised, Double-blind, Triple Dummy Study to Compare Single Inhaler Triple Therapy, Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) With Multiple Inhaler Therapy (Budesonide/Formoterol Plus Tiotropium) Based on Lung Functi [NCT03478696] | Phase 4 | 732 participants (Actual) | Interventional | 2018-06-25 | Completed | ||
| Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease [NCT02500784] | Phase 2 | 0 participants (Actual) | Interventional | 2023-01-31 | Withdrawn(stopped due to Funding ran out before study started, prior PI left institution.) | ||
| A Single-blind, Randomized, Active-controlled, Multi-center and Phase IV Study to Evaluate the Small Airway Parameters of Fluticasone/Formoterol (Flutiform®) Compared to Fluticasone/Salmeterol in Asthma Patients [NCT02491970] | Phase 4 | 15 participants (Actual) | Interventional | 2015-08-31 | Terminated(stopped due to Difficulty of patients enrollments) | ||
| Open Label, Prospective, Exploratory Study to Investigate the Effect of Inhaled CHF5993 pMDI on Central and Peripheral Airway Dimensions in COPD Patients by Functional Respiratory Imaging [NCT03268226] | Phase 3 | 20 participants (Actual) | Interventional | 2017-11-20 | Completed | ||
| To Evaluate Effectiveness of Aclidinium Bromide/Formoterol Fumarate Dihydrate in Chronic Obstructive Pulmonary Disease [NCT03181880] | Phase 4 | 0 participants (Actual) | Interventional | 2017-12-04 | Withdrawn(stopped due to Study stopped early as AZ have re-prioritised to focus on research to help bring existing and innovative medicines to more patients with asthma and COPD.) | ||
| A Phase III, 12-week, Double-blind, Randomised, Parallel-group, Active-controlled, Multinational, Efficacy and Safety Study of Symbicort® Turbuhaler® 160/4.5 μg 2 Inhalations Twice Daily (Bid) Compared to Oxis® Turbuhaler® 4.5 μg 2 Inhalations Twice Daily [NCT01069289] | Phase 3 | 1,293 participants (Actual) | Interventional | 2010-01-31 | Completed | ||
| A Randomized, Evaluator-Blind, Crossover, Single Dose Study of the Bronchodilator Effect of Formoterol Fumarate in Combination With Mometasone Furoate Metered Dose Inhaler Delivered With and Without a Spacer Versus Placebo and Foradil® Aerolizer® in Child [NCT01258803] | Phase 2 | 92 participants (Actual) | Interventional | 2010-12-31 | Completed | ||
| Impact of Fixed TRIple Therapy With Beclometasone/Formoterol/Glycopyrronium DPI (Trimbow® in NEXThaler Device) in Chronic Obstructive PulmoNary Disease in rEal-world Settings: Health-related Quality of Life Patient' eXpectations and characterisTics: the T [NCT05948891] | 500 participants (Anticipated) | Observational | 2023-07-31 | Not yet recruiting | |||
| A 12-week Randomized, Multiple-Dose, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Assess the Pharmacodynamic Response of Fluticasone Propionate in Fixed-Dose Combination With Formoterol Fumarate in Subjects With COPD [NCT01168310] | Phase 2 | 468 participants (Actual) | Interventional | 2010-08-31 | Completed | ||
| A Randomized, Double-blind, Five-period, Placebo and Active-controlled,Cross-over, Multi-centre, Study Evaluating Single Administration of Three Doses of Inhaled PT005 in Patients With Moderate-to-Severe COPD, Compared to Open- Label Marketed Formoterol ( [NCT00880490] | Phase 1/Phase 2 | 34 participants (Actual) | Interventional | 2008-11-30 | Completed | ||
| A Randomized, Placebo-controlled, Double-blind, Six-way Crossover, Single-dose Exposure Study to Compare the Safety and Efficacy of Fluticasone and Formoterol Combination (FlutiForm™100/10μg and 250/10μg) in a Single Inhaler (SkyePharma HFA MDI) With the [NCT00830102] | Phase 2 | 64 participants (Actual) | Interventional | 2004-10-31 | Completed | ||
| A Phase IV, Open Label, Multicentre, Randomised, 2-way Cross-over Exploratory Clinical Trial Comparing TRIMBOW® pMDI and RELVAR® ELLIPTA® DPI on Lung Stiffness Reduction Assessed Through Area Under the Reactance Curve (AX) in COPD. [NCT04671355] | Phase 4 | 0 participants (Actual) | Interventional | 2021-10-04 | Withdrawn(stopped due to Continuing delays due to COVID-19 pandemic) | ||
| A Phase II, Multicentre, Double-blind, Randomised, 5-way Crossover Study to Test the Non-inferiority of the Acute Bronchodilator Effect of CHF 1535 200/6 µg NEXThaler Versus CHF 1535 100/6 µg NEXThaler in Partially Controlled and Uncontrolled Adult Asthma [NCT02148120] | Phase 2 | 60 participants (Actual) | Interventional | 2014-04-30 | Completed | ||
| A Phase I, Randomized, Double-Blind, Single-Dose, Three-Period, Three-Treatment, Cross-Over Study Evaluating the Pharmacokinetics and Safety of a Single Dose of PT010, a Single Dose of PT009, and a Single Dose of Open-Label Symbicort® Turbohaler® in Healt [NCT02189304] | Phase 1 | 59 participants (Actual) | Interventional | 2014-06-01 | Completed | ||
| Differences of Small Airways Function Between Chronic Obstructive Pulmonary Disease(COPD) and Asthma-copd Overlap(ACO) [NCT03563001] | Phase 4 | 80 participants (Anticipated) | Interventional | 2018-06-20 | Recruiting | ||
| A Randomized, Double-blind, Placebo-controlled, Incomplete Unbalanced, Crossover Study to Assess the Efficacy and Safety of Three Doses of Formoterol Fumarate in Pressair® Compared With Perforomist® Inhalation Solution (20 and 40 μg Open-label) in Moderat [NCT02796651] | Phase 2 | 132 participants (Actual) | Interventional | 2016-06-30 | Completed | ||
| A Randomized, Double-Blind, Single Dose, Six-Treatment, Placebo-Controlled, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Three Doses of PT005, in Patients With Moderate to Severe COPD, Compared With Foradil® Aerolizer® (12 and 24 µg Ope [NCT01349868] | Phase 2 | 50 participants (Actual) | Interventional | 2011-05-31 | Completed | ||
| A Phase 3, Multicenter, Open-label Continuation Study in Moderate to Severe Asthmatic Subjects Who Completed FlutiForm HFA pMDI Study SKY2028-3-005, Incorporating Amendment 1 and 2 [NCT00747318] | Phase 3 | 280 participants (Actual) | Interventional | 2008-09-30 | Completed | ||
| A Randomized, Placebo-controlled, Double-blind, Crossover, Single-dose Exposure Study to Evaluate the Early Bronchodilating Effect of FlutiForm 100/10 µg HFA pMDI and FlutiForm 250/10 µg HFA pMDI, Compared to Placebo in Adult Subjects With Mild to Moderat [NCT00734292] | Phase 2 | 39 participants (Anticipated) | Interventional | 2008-09-30 | Completed | ||
| Randomized, Parallel-group Trial to Evaluate Feasibility, Safety and Efficacy of Nebulized Long-Acting Bronchodilators (Formoterol and Revefenacin) vs. Short-Acting Bronchodilators (Albuterol and Ipratropium) in Hospitalized Patients With AECOPD [NCT04655170] | Phase 4 | 60 participants (Anticipated) | Interventional | 2020-12-09 | Recruiting | ||
| Study Comparing Bronchodilator Efficacy of Two Dry Powder Inhalers, Budesonide/Formoterol Easyhaler and Symbicort Turbuhaler; a Randomised, Double-blind, Double-dummy, Multicentre, Single Dose, Crossover Study in Asthmatic Subjects [NCT02308098] | Phase 3 | 72 participants (Actual) | Interventional | 2014-12-31 | Completed | ||
| A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Low-Dose Inhale [NCT00383552] | Phase 3 | 746 participants (Actual) | Interventional | 2006-09-30 | Completed | ||
| A Randomized, Double-blind, Placebo-controlled, Parallel Group, Stratified, Multi-center, 12-Week Study Comparing the Safety and Efficacy of Fluticasone and Formoterol Combination (FlutiForm(tm) 100/10 µg or 250/10 µg Twice Daily) in a Single Inhaler (Sky [NCT00393952] | Phase 3 | 557 participants (Actual) | Interventional | 2006-06-30 | Completed | ||
| Cardiovascular Consequences of Prolonged Inhaled Short-acting Beta-agonist Use in Healthy Participants [NCT06027606] | Phase 1 | 90 participants (Anticipated) | Interventional | 2023-09-01 | Recruiting | ||
| Inspiratory Capacity and HRCT Comparison of Nebulized Arformoterol (Brovana) vs. Dry-powder Inhaler Salmeterol (Serevent) [NCT01361984] | Phase 4 | 20 participants (Anticipated) | Interventional | 2011-06-30 | Recruiting | ||
| A Retrospective Evaluation of the Effectiveness of Fixed-dose Combination Inhaled Corticosteroid /. Long-acting Beta Agonist (ICS/LABA) Therapy in the Management of Asthma in a Representative UK Primary Care Population [NCT01141465] | 815,377 participants (Actual) | Observational | 2001-01-31 | Completed | |||
| "COPDGene Ancillary Proposal: Symbicort Intervention in Airway Predominant" [NCT01253473] | Phase 4 | 46 participants (Actual) | Interventional | 2012-04-30 | Completed | ||
| Effects on Small Airways Obstruction of Two Long-term Treatments With Extrafine Beclomethasone/Formoterol vs Fluticasone/Salmeterol in Asthma [NCT01255579] | Phase 4 | 10 participants (Actual) | Interventional | 2007-07-31 | Completed | ||
| A Phase IV, 12-week, Randomised, Double-blind, Triple Dummy Study to Compare Single Inhaler Triple Therapy, Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) With Multiple Inhaler Therapy (Budesonide/Formoterol Plus Tiotropium) Based on Lung Functi [NCT03478683] | Phase 4 | 729 participants (Actual) | Interventional | 2018-06-25 | Completed | ||
| Physiological Responses to U-LABA/ICS With Emphasis on Exercise Performance in Well-Trained Individuals, Formoterol [NCT06105671] | 24 participants (Anticipated) | Interventional | 2023-12-15 | Not yet recruiting | |||
| A Multi-centre, Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Anti-IgE Monoclonal Antibody to Treat Allergic Asthma Patients Not Adequately Controlled Despite Med/High ICS/LABA. [NCT03468790] | Phase 3 | 393 participants (Actual) | Interventional | 2018-05-09 | Completed | ||
| A 12-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Parallel-group Study to Assess the Efficacy of Indacaterol (150 μg o.d.) in Patients With Chronic Obstructive Pulmonary Disease, Using Formoterol (12 μg b.i.d.) as an Active Control [NCT01377428] | Phase 4 | 0 participants (Actual) | Interventional | 2011-09-30 | Withdrawn | ||
| A Study to Assess the Pharmacokinetics and Safety of PT010 in Subjects With Moderate to Severe COPD Following Single and Repeat Dose Administration [NCT03250182] | Phase 1 | 30 participants (Actual) | Interventional | 2017-08-11 | Completed | ||
| A Phase IIa, Open-Label, Repeat-Dose Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide/Formoterol Fumarate Fixed Dose Combination Administered Twice-Daily by Inhalation in Chinese Patients With Moderate to Seve [NCT03276078] | Phase 2 | 20 participants (Actual) | Interventional | 2017-11-23 | Completed | ||
| Pharmacokinetic Pilot Study on Budesonide/Formoterol Easyhalers and Symbicort Turbuhaler; an Open, Randomised, Single Centre, Single Dose Study With Crossover Design in Healthy Subjects [NCT01181063] | Phase 1 | 20 participants (Actual) | Interventional | 2010-08-31 | Completed | ||
| Comparative Study Between Three Therapeutic Options for Treatment of Chronic Obstructive Pulmonary Disease Patients [NCT04520230] | Phase 4 | 45 participants (Actual) | Interventional | 2014-10-31 | Completed | ||
| Open-labeled Trial to Evaluate the Therapeutic Effects of Inhaled BUDESONIDE/FORMOTEROL in Bronchiolitis Obliterans After Allogeneic Stem Cell Transplantation [NCT01560689] | Phase 2 | 32 participants (Actual) | Interventional | 2008-06-30 | Completed | ||
| "A Randomised, Double Blind, Placebo Controlled, Parallel-group Study With Use of Budesonide/Formoterol As-needed, or Terbutaline As-needed or Regular Use of Budesonide + Terbutaline As-needed, in Patients With Mild Intermittent Asthma" [NCT00989833] | Phase 2 | 66 participants (Actual) | Interventional | 2009-09-30 | Completed | ||
| A Randomised, Double-Blind, Placebo- and Active-Controlled, Incomplete Crossover Efficacy and Safety Comparison of 4-week Treatment Periods of Once Daily Treatment of 4 Doses of BI 1744 CL Inhalation Solution Delivered by the Respimat® in Patients With As [NCT01013753] | Phase 2 | 198 participants (Actual) | Interventional | 2010-02-28 | Completed | ||
| A 12 Week Randomized, Double-blind, Double-Dummy, Placebo-controlled Trial of Symbicort TM (160/4.5mcg) Versus Its Mono-Products (Budesonide and Formoterol) in Children (at Least 6years of Age) and Adults With Asthma-SPRUCE 80/4.5 [NCT00651651] | Phase 3 | 450 participants (Anticipated) | Interventional | 2002-08-31 | Completed | ||
| A 4-week, Phase-II, Double-blind, Placebo-controlled, Randomised, Parallel-group, Multi-centre Study to Assess the Efficacy and Tolerability/Safety of Inhaled AZD3199 Once Daily Compared to 9 μg Formoterol Bid and Placebo in Patients With Moderate to Seve [NCT00929708] | Phase 2 | 329 participants (Actual) | Interventional | 2009-06-30 | Completed | ||
| [NCT01108627] | Phase 4 | 0 participants (Actual) | Interventional | 2010-10-31 | Withdrawn(stopped due to Drug supply sponsor sent outdated drug) | ||
| A Randomized, Double-blind, Placebo-controlled, Parallel, Stratified, Multi-center, 12-Week Study Comparing the Safety & Efficacy of Fluticasone and Formoterol Combination (FlutiForm(tm)100/10 µg Twice Daily) in a Single Inhaler (SkyePharma HFA pMDI)With [NCT00393991] | Phase 3 | 475 participants (Actual) | Interventional | 2006-07-31 | Completed | ||
| A Randomised, Double-blind, Double-dummy, Crossover Efficacy and Safety Comparison of 6-week Treatment Periods of the Free Combination of Tiotropium Inhalation Powder Capsule (18 μg) + Formoterol Inhalation Powder Capsule (12 μg) QD, Tiotropium Inhalation [NCT02238119] | Phase 2 | 74 participants (Actual) | Interventional | 2002-02-28 | Completed | ||
| A Single-Dose, Randomized, Open-Label, Two-Treatment, Three-Period, Three-Sequence, Three-Way Crossover, Partial Replicate, Oral BE Pivotal Study of SYN010 HFA 160/4.5 Inhaler and Symbicort® 160/4.5 in Healthy Volunteers Without Charcoal Block [NCT04494321] | Phase 1 | 99 participants (Actual) | Interventional | 2017-06-19 | Completed | ||
| Effectiveness of Single Inhaler Maintenance and Reliever Therapy With Spiromax® Budesonide/Formoterol (SMART) Versus Fixed Dose Treatment With Diskus® Fluticasone/Salmeterol in Patients With a Chronic Obstructive Pulmonary Disease (COPD) [NCT02477397] | Phase 3 | 201 participants (Actual) | Interventional | 2015-05-01 | Active, not recruiting | ||
| Outcomes in Real-life After Initation Of treatmeNt With Trixeo (Budesonide / Glycopyrronium / Formoterol), a Non-interventional, Multi-centre, Prospective Cohort Study in Italian Routine Care Setting [NCT05862545] | 250 participants (Anticipated) | Observational | 2023-06-01 | Recruiting | |||
| Impact of Exercise on Lung Function in Patients With Chronic Obstructive Pulmonary Disease [NCT03551197] | Phase 4 | 50 participants (Anticipated) | Interventional | 2018-06-13 | Recruiting | ||
| A 24 Week Treatment, Multicenter, Randomized, Double Blinded, Double Dummy, Parallel-group, Clinical Trial Evaluating the Efficacy and Safety of Aclidinium Bromide 400 μg/Formoterol Fumarate 12 μg Fixed-dose Combination BID Compared With Each Monotherapy [NCT02796677] | Phase 3 | 1,595 participants (Actual) | Interventional | 2016-07-05 | Completed | ||
| A Randomized, Phase IIIb, Three-period, Three-treatment, Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects With Moderate to Very Severe COPD After 4 Weeks of Treatment With PT003, Open-Label Spiriva® Res [NCT02347072] | Phase 3 | 80 participants (Actual) | Interventional | 2015-02-01 | Completed | ||
| IKANOS: A Prospective, Open-Label, Minimally Interventional Hybrid Study in the US Comparing Initiation of Breztri Maintenance Versus Any Non-Triple Inhaled Therapy at Discharge After a Hospitalization for a COPD Exacerbation [NCT05970263] | Phase 4 | 1,000 participants (Anticipated) | Interventional | 2024-01-15 | Not yet recruiting | ||
| A Randomized, Double-blind, Positive and Placebo-controlled, Single-dose, Crossover Study of the Effects of CHF5993 pMDI (BDP/FF/GB) at the Proposed Therapeutic and Supratherapeutic Doses, on the Cardiovascular Safety in Healthy Subjects [NCT05830071] | Phase 1 | 95 participants (Actual) | Interventional | 2023-03-29 | Completed | ||
| A Two-Week, Randomized, Modified-Blind, Double-Dummy, Parallel-Group Efficacy and Safety Study of Arformoterol Tartrate Inhalation Solution Twice-Daily, Tiotropium Once-Daily, and Arformoterol Tartrate Inhalation Solution Twice-Daily and Tiotropium Once D [NCT00424528] | Phase 4 | 235 participants (Actual) | Interventional | 2006-12-31 | Completed | ||
| A Double-blind, Randomised, Cross-over, Multi-centre Study, to Evaluate Onset of Effect in the Morning in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort®Turbuhaler® 320/9 μg, Compared With Seretide® Diskus® 50/500 [NCT00542880] | Phase 4 | 442 participants (Actual) | Interventional | 2007-09-30 | Completed | ||
| A 3-month, Double-blind, Double-dummy, Randomised, Multinational, Multicenter, 2-arm Parallel-group Study Comparing the Efficacy and Safety of Formoterol-HFA pMDI 12µg Twice Daily and Formoterol-DPI 12µg Twice Daily, in Patients With Stable Chronic Obstru [NCT00972140] | Phase 3 | 457 participants (Actual) | Interventional | 2005-08-31 | Completed | ||
| A Phase III, Randomized, Open-Label, Non-Inferiority Comparative Study Between Foraseq Inhalation Capsules 12/200 µg And Formoterol/ Budesonide Inhalation Capsules 12/200 µg Eurofarma In Patients With Asthma [NCT01001364] | Phase 3 | 88 participants (Actual) | Interventional | 2010-02-28 | Completed | ||
| A Two-arm, Randomised, Assessor-blind, Parallel Group Study to Evaluate the Effect of Fluticasone/Formoterol Breath Actuated Inhaler (BAI) and Relvar® Ellipta® DPI on Ventilation Heterogeneity in Subjects With Partially Controlled or Uncontrolled Asthma [NCT02753712] | Phase 3 | 105 participants (Actual) | Interventional | 2016-06-15 | Completed | ||
| Perforomist Versus Foradil Evaluated by Inspiratory Capacity and HRCT [NCT00633776] | Phase 4 | 0 participants (Actual) | Interventional | 2008-03-31 | Withdrawn(stopped due to Sponsor withdrew funding prior to study initiation) | ||
| Real Life Effectiveness of Symbicort Maintenance and Reliever Therapy (SMART) in Asthma Patients Across Asia: SMARTASIA [NCT00939341] | Phase 4 | 862 participants (Actual) | Interventional | 2009-07-31 | Completed | ||
| "a 48-week, Double Blind, Randomized, Multinational, Multicentre, Fixed Combination Beclomethasone Dipropionate Plus Formoterol Fumarate Versus Formoterol in Patients With Severe Chronic Obstructive Pulmonary Disease" [NCT00929851] | Phase 3 | 1,199 participants (Actual) | Interventional | 2009-10-31 | Completed | ||
| A 12-week, Randomized, Parallel-group, Phase III Study Comparing the Efficacy of Once-daily Budesonide/Formoterol Turbuhaler (160/4.5 μg/d) and Twice-daily Budesonide Giona Easyhaler (400 μg/d) During Step-down Period in Well Controlled Asthma [NCT02725242] | Phase 3 | 77 participants (Actual) | Interventional | 2016-03-31 | Completed | ||
| Characterisation of 24-hour FEV1-time Profiles of Inhaled BI 1744 CL and Inhaled Foradil Iin Patients With Chronic Obstructive Pulmonary Disease [NCT00931385] | Phase 3 | 99 participants (Actual) | Interventional | 2009-06-30 | Completed | ||
| A Large Simple Safety Study of Arformoterol Tartrate Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease [NCT00909779] | Phase 3 | 841 participants (Actual) | Interventional | 2009-06-30 | Completed | ||
| An Open-Label, Randomized, Five-Period Cross-over, Single-dose Study to Compare Pharmacokinetics Profiles of Z7200 Medium Strength and Symbicort Turbohaler, With and Without Charcoal Blockade in Healthy Volunteers. [NCT02631941] | Phase 1 | 91 participants (Actual) | Interventional | 2016-01-31 | Completed | ||
| A Randomized, Multicenter, Placebo and Active-Controlled, Single-Dose, 4-Period, Crossover Study to Evaluate the Bronchodilating Effect of SYMBICORT pMDI Versus Advair Diskus and Ventolin HFA. [NCT00646620] | Phase 3 | 48 participants (Actual) | Interventional | 2003-04-30 | Completed | ||
| A 52 wk Randomized, Doubleblind, Single Dummy, Parallel Group Multicenter Phase 3 Study Comparing the Long Term Safety of Symbicort pMDI 4x160/4.5mcg Bid to SymbicortpMDI 2x160/4.5mcg Bid & Budesonide HFA pMDI 4x160mcg Bid in Adult and Adolescent Subjects [NCT00651768] | Phase 3 | 570 participants (Anticipated) | Interventional | 2003-08-31 | Completed | ||
| A 12 Week, Randomized, Double-blind, Double-dummy, Placebo-controlled Trial of Symbicort TM (160/4.5mcg) Versus Its Mono-products (Budesonide and Formoterol) in Adolescents (at Least 12 Years of Age) and Adults With Asthma - SPRUCE 160/4.5 [NCT00652002] | Phase 3 | 450 participants (Anticipated) | Interventional | 2002-07-31 | Completed | ||
| A 12 Week, Randomized, Double-Blind, Double-Dummy, Placebo and Active-controlled Study of Symbicort pMDI Administered Once Daily in Adults and Adolescents With Asthma - STEM [NCT00652392] | Phase 3 | 750 participants (Anticipated) | Interventional | 2003-04-30 | Completed | ||
| A Phase I, Randomized, Double-blind, Single-dose, Partial-replicate, 3-way Cross-over Study to Assess the Total Systemic Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI HFO Compared With BGF MDI HFA [NCT05569421] | Phase 1 | 108 participants (Actual) | Interventional | 2022-10-11 | Completed | ||
| STUDY NUMBER: PMC-101-APT Usability and Adherence of Spiromax® Inhaler Device, Turbohaler® and Diskus® Inhaler Devices for Fixed Combination of Corticosteroid/Long-acting beta2- Agonist, in Adults With Asthma or COPD [NCT02757209] | 84 participants (Actual) | Interventional | 2016-04-30 | Completed | |||
| As Needed Budesonide/Formoterol Combination Versus Regular Budesonide/Formoterol Combination Plus as Needed Terbutaline in Mild-Moderate Persistent Asthma [NCT00849095] | Phase 3 | 860 participants (Actual) | Interventional | 2009-04-30 | Completed | ||
| The Comparisons of the Efficacy and Safety of Inhaled LAMA or LAMA+LABA or ICS+LABA for Patients in COPD C Group With Bronchiectasis [NCT02546297] | Phase 4 | 90 participants (Anticipated) | Interventional | 2017-09-15 | Enrolling by invitation | ||
| Onset of Action of Advair HFA 115/21 in Comparison to Symbicort pMDI 160/4.5 Measured by Impulse Oscillometry, IOS. [NCT00867737] | Phase 4 | 30 participants (Anticipated) | Interventional | 2008-09-30 | Recruiting | ||
| A 12-week, Randomised, Double Blind, Active-controlled, Multi-centre, Phase IIIB Study Comparing the Efficacy and Safety of SYMBICORT® pMDI 160/4.5 mg x 2 Actuations Twice Daily Versus Budesonide HFA pMDI 160 mg x 2 Actuations Twice Daily, in Adult/Adoles [NCT00419757] | Phase 3 | 558 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
| A 12-week, Double-blind, Randomised, Parallel Group, Multi-centre, Study to Evaluate Efficacy and Safety of Budesonide/Formoterol (Symbicort Turbuhaler®) 320/9 µg One Inhalation Twice Daily on Top of Tiotropium (Spiriva®) 18 µg One Inhalation Once Daily [NCT00496470] | Phase 4 | 660 participants (Actual) | Interventional | 2007-05-31 | Completed | ||
| A Comparison of Symbicort Single Inhaler Therapy (Symbicort Turbuhaler 160/4.5 Micrograms, 1 Inhalation b.i.d. Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults - a 26-week, Randomised, Open-label, Parallel-gr [NCT00385593] | Phase 3 | 654 participants (Actual) | Interventional | 2006-09-30 | Terminated | ||
| A Phase IIb, Multi-center, Randomized, Double-blind, Placebo-controlled, Multi-dose, Four-period, Cross-over Study of Two Doses of Formoterol Fumarate MDI (PT005; 7.2 and 9.6 µg Ex-actuator), Administered Twice Daily for 1 Week in Patients With Moderate t [NCT01043601] | Phase 2 | 0 participants (Actual) | Interventional | 2010-07-31 | Withdrawn(stopped due to Similar data obtained in another study [see NCT01085045], therefore study not implemented.) | ||
| [NCT00463866] | Phase 4 | 8,424 participants (Actual) | Interventional | 2007-03-31 | Completed | ||
| Bioequivalence Study Comparing Two Budesonide/Formoterol Fumarate Dihydrate Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler 200/6 µg/Inhalation and Symbicort Turbohaler 200 µg/6 µg/Inhalation [NCT00964535] | Phase 1/Phase 2 | 87 participants (Actual) | Interventional | 2009-09-30 | Completed | ||
| A Multi-centre, Randomised, Double-blind, Cross-over Design Study to Evaluate Efficacy on Exercise Tolerance of Symbicort ®(Budesonide/Formoterol) 320/9μg One Inhalation Twice Daily Compared With Placebo and Oxis® 9μg One Inhalation Twice Daily in Patient [NCT00489853] | Phase 4 | 137 participants (Actual) | Interventional | 2007-07-31 | Completed | ||
| A 26-week Treatment, Multicenter, Randomized, Double Blind, Double Dummy, Placebo-controlled, Adaptive, Seamless, Parallel-group Study to Assess the Efficacy, Safety and Tolerability of Two Doses of Indacaterol (Selected From 75, 150, 300 & 600 µg o.d.) i [NCT00463567] | Phase 2/Phase 3 | 2,059 participants (Actual) | Interventional | 2007-04-30 | Completed | ||
| A Six Month, Randomized, Open-Label, Safety Study of Symbicort (160/4.5mcg) Compared to Pulmicort Turbuhaler in Asthmatic Children Aged Six to Eleven Years - SAPLING [NCT00646529] | Phase 3 | 175 participants (Anticipated) | Interventional | 2002-07-31 | Completed | ||
| Blood and Urinary Concentrations of Inhaled Formoterol in Asthmatic Subjects and Elite Athletes With Asthma [NCT00914654] | Phase 4 | 30 participants (Anticipated) | Interventional | 2009-07-31 | Not yet recruiting | ||
| Randomised Cross-over Study to Compare the Effect of Formoterol Plus Tiotropium Versus Formoterol Monotherapy on Breathlessness, Dynamic Hyperinflation and Exercise Tolerance in Moderate-to-severe Stable COPD Patients [NCT00680056] | Phase 4 | 33 participants (Actual) | Interventional | 2007-11-30 | Completed | ||
| An Open-Label, Randomized, Multiple Dose, 3-Way Crossover Study of Arformoterol Tartrate Inhalation Solution and Foradil® (Racemic Formoterol) in Subjects With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) [NCT00685529] | Phase 2 | 24 participants (Actual) | Interventional | 2005-04-30 | Completed | ||
| A Double-Blind, Double-Dummy, Randomized, Placebo- and Active-Controlled, Multicenter, Parallel-Group Study of (R,R)-Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease [NCT00685841] | Phase 3 | 717 participants (Actual) | Interventional | 2002-02-28 | Completed | ||
| A Cumulative Dose Safety and Tolerability Crossover Study of Arformoterol Tartrate Inhalation Solution and Levalbuterol Hydrochloride Inhalation Solution in Pediatric Subjects (Aged 2 to 11 Years of Age) With Asthma [NCT00583947] | Phase 2 | 53 participants (Actual) | Interventional | 2008-01-31 | Completed | ||
| Effect of Methacholine, Long-acting M-cholinolytic and beta2-agonist on the Binding Activity of Beta-receptors in Healthy Volunteers [NCT04137029] | 20 participants (Anticipated) | Interventional | 2019-04-24 | Recruiting | |||
| A Randomized, Double-blind, Double-dummy, Multi-centre, 4-way Cross-over Study to Compare the Single Dose Bronchodilatory Effect of Formoterol Fumarate in Combination With Mometasone Furoate Delivered Via Pressurized Metered Dose Inhaler (pMDI) to Placebo [NCT00746330] | Phase 2 | 32 participants (Actual) | Interventional | 2008-08-31 | Completed | ||
| Comparison of Different Methodologies Assessing Airway Responsiveness and Investigation of Treatment Efficacy of Budesonide /Formoterol in Asthmatics [NCT02574975] | Phase 4 | 80 participants (Anticipated) | Interventional | 2015-04-30 | Recruiting | ||
| A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 ug] and 10 ug [2 Actuations of 5 ug]) Delivere [NCT00796653] | Phase 3 | 937 participants (Actual) | Interventional | 2009-01-31 | Completed | ||
| Clinical Efficacy and Safety of Budesonide and Formoterol in the Management of Non-Cystic Fibrosis Bronchiectasis [NCT00728715] | 40 participants (Anticipated) | Interventional | 2004-01-31 | Completed | |||
| Yiqi Huoxue Huatan Granule for Reducing Mortality in COPD With Chronic Respiratory Failure: A Randomized, Double-blind, Placebo Controlled Trial [NCT04208581] | Phase 3 | 372 participants (Anticipated) | Interventional | 2019-10-08 | Enrolling by invitation | ||
| A Randomized, Multicenter, Placebo and Active-controlled, Single-dose, 4-period, Crossover Study to Evaluate the Bronchodilating Effect of SYMBICORT pMDI Versus Advair Diskus and Ventolin HFA. [NCT00646009] | Phase 3 | 48 participants (Anticipated) | Interventional | 2003-03-31 | Completed | ||
| A 12 Week, Randomized, Double-Blind, Double-Dummy, Active-Controlled Study of SYMBICORT pMDI Administered Once Daily in Children and Adolescents 6 to 15 Years of Age With Asthma - SPROUT [NCT00646321] | Phase 3 | 540 participants (Anticipated) | Interventional | 2003-04-30 | Completed | ||
| A 12 Week Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Trial of Symbicort TM (40/4.5 Mcg) Versus Its Mono-Products (Budesonide and Formoterol) in Asthmatic Children Aged Six to Eleven Years - SEEDLING 40/4.5 [NCT00651547] | Phase 3 | 405 participants (Anticipated) | Interventional | 2002-07-31 | Completed | ||
| A Double Blind, Double Dummy, Randomised, Multicentre, Four Arm Parallel Group Study to Assess the Efficacy and Safety of FlutiForm® pMDI 250/10µg (2 Puffs Bid) vs Fluticasone pMDI 250µg (2 Puffs Bid) Plus Formoterol pMDI 12µg (2 Puffs Bid) Administered C [NCT00734318] | Phase 3 | 1,667 participants (Actual) | Interventional | 2008-09-30 | Completed | ||
| Pharmacokinetic Pilot Study on Budesonide/Formoterol Device-metered Dry Powder Inhaler, Symbicort Turbuhaler; an Open, Single Center, Single Dose Study With 3-way Crossover Design in Healthy Subjects [NCT00868426] | Phase 1 | 12 participants (Actual) | Interventional | 2009-04-30 | Completed | ||
| A Single-Dose, Randomized, Open-Label, 2-Treatment, 3-Period, 3-Sequence, 3-Way Crossover, Partial Replicate, Oral Bioequivalence Pivotal Study of SYN010 HFA Inhaler and Symbicort® 160/4.5 in Healthy Volunteers With Charcoal Block [NCT02850484] | Phase 1 | 99 participants (Actual) | Interventional | 2016-03-31 | Completed | ||
| A Randomized, Multicenter, Open-label, Active-controlled, Single-dose, 5-period, Incomplete Block, Cross-over Study to Evaluate the Relative Bronchodilating Effects of Formoterol When Administered Via Symbicort pMDI or Oxis Turbuhaler to Adults With Stabl [NCT00658255] | Phase 2 | 175 participants (Anticipated) | Interventional | 2002-10-31 | Completed | ||
| Evaluation of the Bronchoprotective Effect of Arformoterol in Children With Exercise Induced Bronchospasm [NCT00662779] | Phase 3 | 0 participants (Actual) | Interventional | 2008-04-30 | Withdrawn(stopped due to High number of screen failures-couldn't find qualified subjects in timely manner) | ||
| A Double-blind, Randomized, Multicenter, Two-part Parallel-group, Dose-ranging Study of Twice-daily and Once-daily (R,R) Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease (COPD) [NCT00691405] | Phase 2 | 215 participants (Actual) | Interventional | 2003-10-31 | Completed | ||
| Comparative Effects of Budesonide and Budesonide/Formoterol (Symbicort) on Asthma Control in Smoking Asthmatic Subjects: A Pilot Study [NCT00691951] | Phase 3 | 0 participants | Interventional | Completed | |||
| Comparing Rapid Bronchodilatory Effect of Formoterol and Salbutamol in Children Between 5-15 Years With Mild to Moderate Acute Exacerbation of Asthma- A Double Blind Randomized Controlled Trial [NCT00900874] | Phase 4 | 78 participants (Anticipated) | Interventional | 2009-01-31 | Recruiting | ||
| An Open-label Phase III, Multi-centre 52-week , Parallel-group Study Evaluating the Safety and Efficacy of Symbicort Turbuhaler 320/9 Twice Daily Compared With Standard Treatment in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) [NCT01070784] | Phase 3 | 328 participants (Actual) | Interventional | 2010-01-31 | Completed | ||
| Double Blind, Double Dummy, Multicentre, Randomised, Placebo- Controlled, Crossover Design Clinical Trial of 12 μg (Single Dose and Repeated Doses) Formoterol Fumarate Administered Via pMDI With HFA-134a Propellant or DPI (Aerolizertm Inhaler) in Patients [NCT00742248] | Phase 2 | 54 participants (Actual) | Interventional | 2004-09-30 | Completed | ||
| A Two Stage Randomized, Open-Label, Parallel Group, Phase III, Multicenter, 7 Month Study to Assess the Efficacy & Safety of SYMBICORT pMDI Adminstered Either as Fixed or as an Adjustable Regimen Versus a Fixed Regimen of Advair in Subjects 12 Yrs of Age [NCT00646594] | Phase 3 | 1,200 participants (Anticipated) | Interventional | 2003-11-30 | Completed | ||
| The Efficacy of Budesonide/Formoterol in Cough Variant Asthma -- A Multi-center Randomized, Controlled Clinical Trial [NCT04171180] | Phase 4 | 500 participants (Anticipated) | Interventional | 2020-05-01 | Recruiting | ||
| A Phase II, Multinational, Multicentre, Double Blind, Double Dummy, Randomised, 5-way Cross-over, Placebo and Active Controlled Clinical Study to Test the Non-inferiority of a Single Dose of CHF 1535 (Fixed Combination of Beclomethasone Dipropionate 100 µ [NCT00868023] | Phase 2 | 69 participants (Actual) | Interventional | 2009-02-28 | Completed | ||
| Pharmacokinetic Study Comparing Two Budesonide/Formoterol Fumarate Dihydrate Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler 320/9 Microg/Inhalation and Symbicort Turbuhaler Forte; a Randomised, Double-blind, Single Centre, Single Dose [NCT01386996] | Phase 1 | 74 participants (Actual) | Interventional | 2011-07-31 | Completed | ||
| Multicenter, Phase III, Randomized, Open Label Study to Evaluate the Efficacy and Safety of a Fixed-dose Combination of Formoterol/Fluticasone and Salmeterol/Fluticasone in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD). [NCT01393145] | Phase 3 | 0 participants (Actual) | Interventional | 2011-08-31 | Withdrawn | ||
| Open-label, Randomized, Single-dose, Placebo-controlled, 4-way Crossover Study to Investigate the Pharmacokinetic Interaction of Glycopyrrolate and Formoterol in Healthy Subjects. [NCT01398111] | Phase 1 | 44 participants (Actual) | Interventional | 2011-05-31 | Completed | ||
| Effect of Charcoal on Gastrointestinal Absorption of Budesonide and Formoterol [NCT01423305] | Phase 1 | 20 participants (Actual) | Interventional | 2011-08-31 | Completed | ||
| A Randomized, Double-blind, Parallel Group, 14-day, Multi-Center Study to Evaluate the Safety of PT003, PT005, PT001 and Foradil® Aerolizer® (12 µg, Open Label) as Evaluated by Holter Monitoring, in Patients With Moderate to Severe Chronic Obstructive Pul [NCT01349803] | Phase 2 | 237 participants (Actual) | Interventional | 2011-05-31 | Completed | ||
| 48-week,Multinational,Randomized,Double-blind,2-parallel Groups,Comparing the Efficacy of Foster for Maintenance and Reliever Versus Fixed-dose Foster for Maintenance Plus Salbutamol as Reliever in Asthmatics >=18 Years of Age [NCT00861926] | Phase 3 | 2,079 participants (Actual) | Interventional | 2009-03-31 | Completed | ||
| A 12-week, Multinational, Randomised, Double Blind, Double Dummy, 4-arm Parallel-group Study Comparing the Efficacy and Safety of CHF 1535 (Fixed Combination of Beclomethasone Dipropionate + Formoterol Fumarate) 100 + 6 μg/Actuation Inhalation Powder, Adm [NCT00862394] | Phase 3 | 783 participants (Actual) | Interventional | 2009-02-28 | Completed | ||
| A Randomized, Multi-center, Parallel Group, Double Blind, Placebo and Formoterol Controlled 14 Day Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Adult and Adolescent Patients With Persistent Asthma [NCT00545272] | Phase 2 | 392 participants (Actual) | Interventional | 2007-10-31 | Completed | ||
| Characterization of 24 Hour Spirometry Profiles of Inhaled BI 1744 CL and Inhaled Foradil in Patients With Chronic Obstructive Pulmonary Disease [NCT00932646] | Phase 3 | 100 participants (Actual) | Interventional | 2009-06-30 | Completed | ||
| A Randomized, Double-blind, Double Dummy Crossover Trial on the Effect of Budesonide/Formoterol and Inhaled Budesonide Alone on Exercise-Induced Asthma in Patients With Persistent Asthma [NCT01070888] | Phase 4 | 6 participants (Actual) | Interventional | 2010-02-28 | Terminated(stopped due to Unable to reach target goal) | ||
| A Double-blind, Randomised, Incomplete Block, Crossover, Placebo-controlled, Dose-response Study to Assess Bronchial Hyperresponsiveness and Airway Inflammation Effects of FlutiForm® pMDI Low and High Dose in Adult Subjects With Mild to Moderate Asthma [NCT00995800] | Phase 2 | 46 participants (Actual) | Interventional | 2009-10-31 | Completed | ||
| A Randomised, Single Blind, Cross-over Study to Compare a Fixed Dose Combination of Fluticasone Propionate / Formoterol Fumarate (Breath Actuated Inhaler (BAI)) With a Fixed Dose Combination of Indacaterol Maleate / Glycopyrronium Bromide (Ultibro® Breezh [NCT02693769] | Phase 2/Phase 3 | 2 participants (Actual) | Interventional | 2016-07-31 | Terminated(stopped due to Recruitment issues) | ||
| A Phase II, Double-blind, Placebo-controlled, Randomised, 6-way Cross-over, Single-dose Study to Investigate the Local and Systemic Effects of 3 Doses of Inhaled AZD3199 (a β2-agonist) Compared to Formoterol in Asthmatic Patients [NCT00736489] | Phase 2 | 37 participants (Actual) | Interventional | 2008-08-31 | Completed | ||
| A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 ug] and 10 ug [2 Actuations of 5 ug]) Delivere [NCT00793624] | Phase 3 | 906 participants (Actual) | Interventional | 2009-02-28 | Completed | ||
| A Comparison of Symbicort® Single Inhaler Therapy (Symbicort Turbuhaler® 160/4.5mg, 1 Inhalation Two Times a Day (b.i.d.) Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults a -26-week, Randomized, Open-label, P [NCT00628758] | Phase 3 | 430 participants (Actual) | Interventional | 2005-12-31 | Completed | ||
| Acute Bronchodilation and Bronchial Inflammation: Nitric Oxyde Concentration in Chronic Obstructive Pulmonary Disease Patients. Stretching of Airways and Nitric Oxide in Bronchodilation, SANOB Study [NCT01853787] | Phase 4 | 49 participants (Actual) | Interventional | 2014-07-31 | Completed | ||
| Open-label, Non-randomized, Parallel-group Study to Investigate the Pharmacokinetics, Safety and Tolerability of a Single Dose of CHF 5993 pMDI in Subjects With Mild, Moderate and Severe Renal Impairment in Comparison With Matched Healthy Control Subjects [NCT02040597] | Phase 1 | 42 participants (Actual) | Interventional | 2014-01-31 | Completed | ||
| Investigating the Mechanism of Inhaled Corticosteroids Associated Pneumonia by Longitudinal Characterisation of the Airway Microbiome in Patients With Severe COPD [NCT02972476] | Phase 4 | 158 participants (Actual) | Interventional | 2016-12-31 | Completed | ||
| Usefulness of Exhaled Breath Condensate and FENO for Evaluation of Markers of Airway Inflammation in Children With Asthma [NCT00961155] | Phase 2 | 200 participants (Anticipated) | Interventional | 2009-08-31 | Recruiting | ||
| Symptom-driven Combination Inhaled Corticosteroids and Long-acting Beta Agonist Therapy for Patients With Asthma Who Are Identified as Non-adherent to Daily Maintenance Inhalers [NCT05111262] | Phase 1/Phase 2 | 60 participants (Anticipated) | Interventional | 2021-12-16 | Recruiting | ||
| An Open-Label, Multi-Center, Patient Handling Study of Mometasone Furoate/Formoterol Fumarate MDI With an Integrated Dose Counter in Adolescent and Adult Subjects and Adult With Asthma or COPD [NCT00604500] | Phase 3 | 272 participants (Actual) | Interventional | 2008-03-01 | Completed | ||
| A 12-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-national, Phase III, Efficacy and Safety Study of Inhaled Formoterol 4.5 μg and 9 μg Twice Daily in Japanese and European Patients With Chronic Obstructive Pulmonary Disease (C [NCT00628862] | Phase 3 | 613 participants (Actual) | Interventional | 2007-12-31 | Completed | ||
| A Randomised, 4-week, Placebo-controlled, Double-blind, 6 Arm Parallel Group, Dose-finding Clinical Trial, to Assess the Efficacy, Safety and Pharmacokinetics of Three Different Doses of Formoterol Combined With the Inhaled Anticholinergic Aclidinium Brom [NCT00626522] | Phase 2 | 808 participants (Actual) | Interventional | 2008-02-29 | Completed | ||
| A 52-Week Efficacy and Safety Non-Inferiority Study of Fluticasone Propionate/Salmeterol 250/50mcg BID Delivered by Dry Powder Inhaler (Diskus) Versus Mometasone Furoate/Formoterol Fumarate 200/10mcg BID Delivered by Pressurized Metered-Dose Inhaler in Pe [NCT00424008] | Phase 3 | 722 participants (Actual) | Interventional | 2007-04-30 | Completed | ||
| A 52-week, Randomised, Double-blind, Parallel-group, Multi-centre, Phase IIIB Study Comparing the Long Term Safety of SYMBICORT® pMDI 160/4.5 mg x 2 Actuations Twice Daily to Budesonide HFA pMDI 160 mg x 2 Actuations Twice Daily in Adult/Adolescent (≥12 Y [NCT00419952] | Phase 3 | 742 participants (Actual) | Interventional | 2007-02-28 | Completed | ||
| A Phase IIIB, 12-Month, Double-blind, Double-dummy,Randomised, Parallel-group, Multicentre Exacerbation Study of SYMBICORT® pMDI 160/4.5 μg x 2 Actuations Twice-daily and 80/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler® 4.5 μg x 2 I [NCT00419744] | Phase 3 | 1,200 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
| A 52-week Treatment, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (300 and 600 µg Once Daily) in Patients With Chronic Obstructive Pulmonary D [NCT00393458] | Phase 3 | 1,732 participants (Actual) | Interventional | 2006-10-31 | Completed | ||
| A 26-Week Placebo-Controlled Efficacy and Safety Study of Mometasone Furoate/Formoterol Fumarate Combination Formulation Compared With Mometasone Furoate and Formoterol Monotherapy in Subjects With Persistent Asthma Previously Treated With Medium-Dose Inh [NCT00383240] | Phase 3 | 781 participants (Actual) | Interventional | 2006-09-30 | Completed | ||
| Randomized, Double Blind, Double Dummy, Placebo Controlled Trial to Compare the Effectiveness of Formoterol vs Ipatropioum Bromide Plus Fenoterol in Asthmatic Children (5-<12 Years) With Acute Bronchial Obstruction Attending Emergency Services [NCT00460577] | Phase 4 | 60 participants (Actual) | Interventional | 2007-03-31 | Completed | ||
| A Phase 3 Randomised Double Blind Randomised Parallel Multinational Trial Comparing a Fixed Combination of Beclometasone+Formoterol+Glycopyrrolate to Foster® in Patients With Chronic Obstructive Pulmonary Disease [NCT01917331] | Phase 3 | 1,368 participants (Actual) | Interventional | 2014-03-31 | Completed | ||
| A Six-Week, Randomized, Double-Blind, Quadruple-Dummy Parallel Group Multiple Dose Study Comparing the Efficacy and Safety of Tiotropium Inhalation Capsules Plus Formoterol Inhalation Capsules to Salmeterol Inhalation Aerosol Plus Fluticasone Inhalation A [NCT00239421] | Phase 4 | 605 participants | Interventional | 2003-11-30 | Completed | ||
| A Randomised, Double-blind, Double Dummy, Parallel Group Study Comparing Fluticasone Propionate / Formoterol Fumarate (Flutiform®) 250/10 µg (2 Puffs BID) and Flutiform® 125/5 µg (2 Puffs BID) Versus Formoterol Fumarate Dihydrate (Atimos®) 12 µg (1 Puff B [NCT01946620] | Phase 3 | 1,767 participants (Actual) | Interventional | 2013-10-31 | Completed | ||
| [NCT00215384] | Phase 2 | 35 participants | Interventional | Completed | |||
| [NCT00215423] | Phase 2 | 49 participants | Interventional | Completed | |||
| Change of Inspiratory Peak Flow After Bronchial Dilatation on Patients With Moderate to Severe COPD [NCT00561886] | Phase 4 | 40 participants (Actual) | Interventional | 2007-04-30 | Completed | ||
| Open, Randomised, Parallel Group Multicentre Study to Compare the Efficacy & Safety of Flutiform® pMDI vs Fluticasone pMDI Plus Formoterol DPI in Adolescent & Adult Subjects With Mild to Moderate-severe Persistent, Reversible Asthma [NCT00563056] | Phase 3 | 227 participants (Actual) | Interventional | 2007-09-30 | Completed | ||
| A Comparative Study of Efficacy and Safety of Genolar® and Xolar® in Treating Patients With Moderate to Severe Persistent Atopic Bronchial Asthma Inadequately Controlled With Stage 4 GINA (2017) Treatment [NCT04607629] | Phase 3 | 192 participants (Actual) | Interventional | 2018-06-20 | Completed | ||
| An Open, Phase III, Multicentre, 52-week Study, Evaluating the Safety and Efficacy of Symbicort® Turbuhaler® (1, 2, and 4 x 160/4.5 µg Twice Daily) in Japanese Patients With Asthma [NCT00255255] | Phase 3 | 120 participants | Interventional | 2005-11-30 | Completed | ||
| The Value of FeNO, Blood Eosinophils and TIgE in Predicting the Response to Corticosteroid in Patients With Chronic Cough [NCT05888350] | 520 participants (Anticipated) | Interventional | 2023-07-30 | Not yet recruiting | |||
| A Pilot Comparative Study of the Genomic Molecular and Clinical Profiles of Patients With Lung Cancer, COPD, or Asthma Treated With Symbicort Turbuhaler [NCT00569712] | Phase 1 | 30 participants (Actual) | Interventional | 2007-01-31 | Completed | ||
| Trainability of the beta2-adrenergic System With Respect to Performance [NCT04616261] | 30 participants (Anticipated) | Interventional | 2020-11-10 | Not yet recruiting | |||
| A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (7 Days), Four-Period, Eight-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Two Doses of PT003, Two Doses of PT005 and [NCT01085045] | Phase 2 | 118 participants (Actual) | Interventional | 2010-03-31 | Completed | ||
| Efficacy and Safety of Three Doses of Aclidinium Bromide Compared to Placebo and to an Active Comparator All Administered Twice Daily by Inhalation in Patients With Stable Moderate and Severe Chronic Obstructive Pulmonary Disease (COPD). [NCT01120093] | Phase 2 | 79 participants (Actual) | Interventional | 2010-05-31 | Completed | ||
| recipientsProspective Evaluation of the Efficacy of Budesonide/Formoterol (Symbicort®) in Bronchiolitis Obliterans in Allogeneic Haematopoietic Stem Cell Transplantation (AHSCT) Recipients [NCT00624754] | Phase 2 | 32 participants (Actual) | Interventional | 2008-03-31 | Completed | ||
| A 12-week Phase III Study to Evaluate the Efficacy and Tolerability of Beclomethasone Dipropionate/Formoterol Single Inhaler HFA 134a-pMDI in Adult Patients With Mild to Moderate Persistent Asthma [NCT00862264] | Phase 3 | 286 participants (Actual) | Interventional | 2004-08-31 | Completed | ||
| A Proof Of Concept Study To Evaluate Tiotropium as Add-on Therapy to Inhaled Budesonide/Formoterol Combination in COPD [NCT00996697] | Phase 4 | 23 participants (Actual) | Interventional | 2006-10-31 | Completed | ||
| A Single Arm, 12 Week, Multicentre, Open Label, Phase IV Study to Evaluate Correct Use of and Patient Satisfaction From Sequential Use of Formoterol and Budesonide Inhaler Capsules Via Aerolizer™ Device in Patients With Asthma. [NCT00997477] | Phase 4 | 0 participants (Actual) | Interventional | 2010-06-30 | Withdrawn | ||
| A Real-world, Multicenter, 52-week Prospective Cohort Study to Capture the Reasons for Switch to Triple Combination Therapy and to Assess the Clinical and Patient Reported Outcomes in Adults With Moderate to Severe COPD Treated With Trixeo Aerosphere™ in [NCT05915182] | 200 participants (Anticipated) | Observational | 2023-07-21 | Recruiting | |||
| A Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota [NCT02833480] | Phase 2 | 69 participants (Anticipated) | Interventional | 2015-02-28 | Recruiting | ||
| A Rand, Doubleblind, Activecontrolled, Parallel-grp,Singledummy, Multicenter,12 wk Study to Assess the Effic.&Safety of Symbicort pMDI 2x160/4.5mcg QD Compared to Symb. pMDI 2x80/4.5mcg QD, Symb. pMDI 2x80/4.5mcg Bid and to Budesonide pMDI 2x160 Mcg QD in [NCT00646516] | Phase 3 | 615 participants (Anticipated) | Interventional | 2003-10-31 | Completed | ||
| Efficacy, Safety and Tolerability of Two Fixed-Dose Combinations of Aclidinium Bromide With Two Doses of Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo All Administered Twice Daily in Stable, Moderate to Severe Chron [NCT01078623] | Phase 2 | 176 participants (Actual) | Interventional | 2010-02-28 | Completed | ||
| Switch of Budesonide-formoterol Dry Powder Inhalers at Pharmacy in Norway; A Retrospective, Observational Study to Evaluate the Impact on Disease Control in Patients With Asthma and/or Chronic Obstructive Pulmonary Disease (COPD) [NCT04663386] | 29 participants (Actual) | Observational | 2020-12-10 | Terminated(stopped due to Target recruitment not reached) | |||
| A Single-dose, Open-label, Randomized, 2-way Cross-over Study of CHF 1535 35/4 NEXThaler® (Fixed Combination of Beclometasone Dipropionate (BDP) 35 μg Plus Formoterol Fumarate (FF) 4 μg Versus the Free Combination of Licensed BDP DPI (Dry Powder Inhaler) [NCT02787967] | Phase 2 | 26 participants (Actual) | Interventional | 2016-08-31 | Completed | ||
| Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study [NCT01432080] | Phase 2 | 12 participants (Actual) | Interventional | 2011-09-30 | Terminated(stopped due to Not meeting recruitment targets) | ||
| An Open-Label, Single-dose, Randomized, Five-Period Cross-over to Compare Pharmacokinetics Profiles of Z7200 and Symbicort Turbohaler, With and Without Charcoal Blockade in Healthy Volunteers. [NCT02237508] | Phase 1 | 90 participants (Actual) | Interventional | 2014-09-30 | Completed | ||
| A Double-Blind, Multicentre, Randomized, Three-Period, Three-Treatment, Cross-Over Study to Evaluate the Effect of BGF MDI, BFF MDI, and Placebo MDI on Exercise Parameters in Participants With COPD (ATHLOS) [NCT06067828] | Phase 3 | 180 participants (Anticipated) | Interventional | 2023-10-24 | Recruiting | ||
| A 6-Month Double-Blind, Double-Dummy, Randomized, Parallel Group, Multicenter Efficacy & Safety Study of SYMBICORT® pMDI 2 x 160/4.5 µg & 80/4.5 µg Bid Compared to Formoterol TBH, Budesonide pMDI (& the Combination) & Placebo in COPD Patients [NCT00206154] | Phase 3 | 1,500 participants (Anticipated) | Interventional | 2005-04-30 | Completed | ||
| A Single-dose, Open-Label, 2-Way Cross-Over, Clinical Pharmacology Study Of Chf 1535 50/6 HFA pMDI (Fixed Combination Of Beclomethasone Dipropionate 50µg Plus Formoterol Fumarate 6 µg) Using The Aerochamber Plus™ Spacer Device Versus The Free Combination [NCT01848769] | Phase 2 | 20 participants (Actual) | Interventional | 2009-09-30 | Completed | ||
| [NCT00215358] | Phase 2 | 32 participants | Interventional | 2002-07-31 | Completed | ||
| [NCT00215397] | Phase 2 | 16 participants | Interventional | Completed | |||
| A 12-week Double-Blind, Parallel-Group, Placebo- and Active- Controlled Trial to Evaluate the Efficacy and Safety of Formoterol Fumarate Inhalation Solution 20 Mcg in the Treatment of Patients With Chronic Obstructive Pulmonary Disease [NCT00215436] | Phase 3 | 345 participants | Interventional | 2005-03-31 | Completed | ||
| The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers: a Randomized, Double-blind, Placebo-controlled, Cross-over Trial [NCT03104634] | Phase 3 | 43 participants (Actual) | Interventional | 2017-05-01 | Completed | ||
| A Randomized, Multi-center, Parallel Group, Double Blind, Placebo and Formoterol Controlled 14 Day Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via TWISTHALER® Device in Patients With COPD [NCT00557466] | Phase 2 | 568 participants (Actual) | Interventional | 2007-10-31 | Completed | ||
| A Phase III, 12-week, Multicentre, Multinational, Randomised, Double-blind, Double-dummy, 3 Arm-parallel Group Study to Test the Efficacy of CHF 1535 (Fixed Combination of Beclomethasone Dipropionate (BDP) Plus Formoterol Fumarate (FF)) Versus a Free Comb [NCT01475032] | Phase 3 | 638 participants (Actual) | Interventional | 2011-09-30 | Completed | ||
| A 24-week Phase III Study to Evaluate the Efficacy and Tolerability of Beclometasone/Formoterol Single Inhaler HFA 134a-pMDI in Adult Patients With Moderate to Severe Persistent Asthma [NCT00476268] | Phase 3 | 824 participants (Actual) | Interventional | 2004-02-29 | Completed | ||
| Randomised, Double-blind, Double-dummy, 52-week, Parallel Group Study of a Standard Dosing Regimen With Salmeterol/Fluticasone propionate50/250 Twice Daily Diskus Versus a Symptom-driven, Variable Dosing Regimen With Formoterol/Budesonide Combination 4.5/ [NCT00479739] | Phase 4 | 700 participants (Actual) | Interventional | 2002-11-30 | Completed | ||
| "A 48-week, Double Blind, Double Dummy, Randomised, Multinational, Multicentre, 3-arm Parallel Group Clinical Study of Fixed Combination Beclometasone Dipropionate Plus Formoterol Fumarate Administered Via pMDI With HFA-134a Propellant Versus Fixed Combin [NCT00476099] | Phase 3 | 828 participants (Actual) | Interventional | 2006-12-31 | Completed | ||
| Retrospective, Real-life Observational, Matched Cohort Evaluation of the Effectiveness of BDP/FOR (Fostair® 100/6) and FP/SAL (Seretide® 125) in Patients Switching From Seretide to Fostair in UK Primary Care Asthma Management [NCT01242098] | 137 participants (Actual) | Observational | 2008-01-31 | Completed | |||
| A 6-Week Trial to Compare the Efficacy and Safety of Concomitant Treatment With Formoterol Fumarate Inhalation Solution 20 Mcg Twice Daily and Tiotropium 18 Mcg Once Daily to Tiotropium 18 Mcg Once Daily Alone in the Treatment of Patients With Chronic Obs [NCT00507234] | Phase 3 | 128 participants (Actual) | Interventional | 2007-03-31 | Completed | ||
| Use of Buventol Easyhaler and Bufomix Easyhaler as Relievers in Methacholine Challenge Testing and Inspiratory Flow Profiles During Induced Bronchoconstriction in Adult Subjects [NCT05084222] | Phase 4 | 180 participants (Actual) | Interventional | 2021-11-11 | Completed | ||
| [NCT02934945] | Phase 4 | 30 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting | ||
| A Two-week, Randomised, Double-blind Study Assessing the Onset of Effect Questionnaire Administered Pre-dose Versus Post-dose in Adult Subjects (≥ 18 Years) With Mild to Moderate Asthma, Receiving SYMBICORT® pMDI 80/4.5 μg x 2 Actuations Twice Daily or Bu [NCT00449501] | Phase 3 | 134 participants (Actual) | Interventional | 2007-03-31 | Completed | ||
| A Randomized, Double-blind, Two-way Cross-over Study Evaluating Systemic Bioavailability and Airway Clearance of SymbicortTurbuhaler 320/9mcg vs SeretideDiskus 50/500mcg After Single Inhalations in Patients With COPD and Healthy Volunteers [NCT00379028] | Phase 4 | 54 participants (Actual) | Interventional | 2006-09-30 | Completed | ||
| A Prospective Non-interventional Study in Patients With Chronic Obstructive Pulmonary Disease That Evolve to Fixed Long-acting Muscarinic Antagonist/Long-acting beta2-agonist/Inhaled Corticosteroid Triple Therapy, Trimbow® [NCT03627858] | 149 participants (Actual) | Observational | 2018-08-01 | Completed | |||
| An Investigator Initiated, Randomized, Double Blind, Placebo Controlled Study to Assess the Effect of Glycopyrrolate/Formoterol on Exercise Tolerance and Dynamic Hyperinflation in Patients With Chronic Obstructive Pulmonary Disease. [NCT03081156] | Phase 4 | 52 participants (Actual) | Interventional | 2017-03-27 | Completed | ||
| Formoterol-beclomethasone in Patients With Bronchiectasis: a Randomized Controlled Trial [NCT03846570] | Phase 3 | 34 participants (Actual) | Interventional | 2019-01-29 | Terminated(stopped due to Insufficient inclusion rate (due to COVID-19 pandemic)) | ||
| A Multicenter, Open-Label, Randomized, Active-Controlled, Parallel Group Chronic Safety Study of (R,R)-Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease [NCT00064415] | Phase 3 | 799 participants (Actual) | Interventional | 2002-06-30 | Completed | ||
| Effects of High Dose Inhaled Budesonide+ Formoterol Versus Placebo and Oral Prednisolone on Biomarkers of Airway Inflammation in the Treatment of Exacerbations in Non-hospitalised Patients With Mild to Moderate COPD. [NCT00239278] | Phase 2 | 120 participants | Interventional | 2001-01-31 | Completed | ||
| A Comparison of Symbicort Single Inhaler and Conventional Best Practice for the Treatment of Persistent Asthma in Adolescents and Adults - a 26-week, Randomised, Open, Parallel Group Multicentre Study [NCT00259792] | Phase 3 | 1,000 participants | Interventional | 2004-09-30 | Completed | ||
| A Comparative, Placebo-controlled, Double Blind, Double Dummy, Cross-over, Single Centre, Phase IIIb Study Between Formoterol Alone (Oxis® Turbuhaler® 4.5 µg) and the Fixed Combination of Formoterol and Budesonide (Symbicort® Turbuhaler®160/4.5 µg) on Air [NCT00288379] | Phase 3 | 16 participants | Interventional | 2004-10-31 | Completed | ||
| A 6-Week Double-Blind, Parallel-Group, Active-Controlled Trial to Compare the Efficacy and Safety of Concomitant Treatment of Formoterol Fumarate Inhalation Solution 20 Mcg Twice Daily and Tiotropium 18 Mcg Once Daily to Tiotropium 18 Mcg Once Daily Alone [NCT00308191] | Phase 3 | 128 participants | Interventional | 2006-04-30 | Completed | ||
| ADVICE: A Dose Range Finding Study of Formoterol Administered Once Daily in the Evening in Combination With Ciclesonide Using the Ultrahaler™ Versus Monotherapy of Each Drug in Asthmatic Patients [NCT00314509] | Phase 2 | 240 participants | Interventional | 2005-07-31 | Completed | ||
| A Comparison of Budesonide/Formoterol Turbuhaler® 160/4.5 µg 2 Inhalations BID Plus as Needed to Budesonide Turbuhaler® 320 µg 2 Inhalations BID Plus Terbutaline Turbuhaler® 0.4 mg as Needed for the Prevention of Asthma Relapse [NCT00326053] | Phase 3 | 600 participants (Anticipated) | Interventional | 2006-05-31 | Completed | ||
| Real Life Effectiveness in Asthma of Symbicort Single Inhaler Therapy [NCT00319306] | Phase 3 | 550 participants | Interventional | 2005-09-30 | Completed | ||
| Expertise Asthma COPD Program With Digital Support [NCT05831566] | Phase 3 | 138 participants (Anticipated) | Interventional | 2023-01-31 | Recruiting | ||
| Efficacy and Safety of Formoterol Certihaler, Tiotropium HandiHaler and Tiotropium HandiHaler in Combination With Formoterol Certihaler in Patients With Stable Chronic Obstructive Pulmonary Disease [NCT00134979] | Phase 4 | 847 participants (Actual) | Interventional | 2004-10-31 | Completed | ||
| A Randomized, Multi-centre, Double-blind, Double Dummy Placebo Controlled Single-dose Cross-over Study to Demonstrate That 12 and 24 µg of Formoterol Delivered by Concept1 Has a Bronchodilator Efficacy Which is Equivalent to the Same Dose of Formoterol De [NCT00443482] | Phase 2 | 50 participants (Actual) | Interventional | 2007-02-28 | Completed | ||
| The Effect of Twice Daily Aclidinium Bromide/Formoterol Fumarate 340/12 mcg vs. Once Daily Tiotropium 'Respimat' 5mcg on Static and Dynamic Hyperinflation in Patients With COPD During 24 Hours [NCT03275116] | Phase 4 | 49 participants (Anticipated) | Interventional | 2017-07-07 | Recruiting | ||
| A Two-week, Randomised, Double-blind Study Assessing the Onset of Effect Questionnaire Administered Daily Versus Weekly in Adult Subjects (≥ 18 Years) With Mild to Moderate Asthma, Receiving SYMBICORT® pMDI 80/4.5 μg x 2 Actuations Twice Daily or Budesoni [NCT00449527] | Phase 3 | 123 participants (Actual) | Interventional | 2007-03-31 | Completed | ||
| [NCT00475813] | Phase 3 | 211 participants (Actual) | Interventional | 2007-03-31 | Completed | ||
| A Randomized, Double-Blind Trial of the Effect of Different Anti-Asthmatic Treatments on Lung Function and on Exercise-Induced Bronchoconstriction in Children With Asthma [NCT00490243] | Phase 4 | 150 participants (Actual) | Interventional | 2003-07-31 | Completed | ||
| A Double-Blind Randomized, Parallel-Group, Multicenter Clinical Study to Compare the Efficacy and Tolerability of Tiotropium Bromide Alone vs. the Co-Administration of Tiotropium Bromide and Formoterol Fumarate in Subjects With COPD [NCT00139932] | Phase 4 | 255 participants (Actual) | Interventional | 2005-09-01 | Completed | ||
| Modified-blind, Randomized, Multicenter, Single Dose, Two-way Crossover Study of Arformoterol Tartrate Inhalation Solution 15 Micrograms Twice A Day Versus 30 Micrograms Once A Day in Subjects With Chronic Obstructive Pulmonary Disease (COPD) [NCT00571428] | Phase 4 | 33 participants (Actual) | Interventional | 2007-11-30 | Completed | ||
| A Pilot Study to Evaluate the Dose-response of Inhaled Formoterol to Inhibit Airway Responsiveness to Methacholine in Patients With Mild Asthma [NCT00643578] | 37 participants (Actual) | Interventional | 2008-03-31 | Completed | |||
| Genotype Stratified Treatment With Anticholinergic vs. Beta-agonist (Long Acting) and Exacerbations (GABLE) [NCT00706446] | 255 participants (Actual) | Interventional | 2008-06-30 | Terminated(stopped due to Funding was terminated) | |||
| Efficacy, Safety, Tolerability, and Pharmacokinetics of Trospium Inhalation Powder (TrIP) Administered to Subjects With Chronic Obstructive Pulmonary Disease (COPD) [NCT00801684] | Phase 2 | 24 participants (Actual) | Interventional | 2009-02-28 | Completed | ||
| A Phase 2a, Randomized, Open-Label, 2-Way Crossover Study To Determine The Pharmacokinetics, Safety, And Tolerability Of Aclidinium/Formoterol 400/12 µg Fixed Dose Combination Via Almirall Inhaler And Formoterol 12 µg Via Foradil® Aerolizer® In Patients W [NCT01551888] | Phase 2 | 24 participants (Actual) | Interventional | 2012-01-31 | Completed | ||
| A Comparison of the Inflammatory Control of Asthma Provided by One Inhalation of Symbicort® Turbuhaler® 160/4.5 µg/Inhalation b.i.d. Plus As-needed Versus One Inhalation of Symbicort® Turbuhaler® 320/9 µg/Inhalation b.i.d. + One Inhalation of Pulmicort® T [NCT00244608] | Phase 3 | 100 participants | Interventional | 2005-05-31 | Completed | ||
| Efficacy and Safety of Symbicort ®Turbuhaler® 160/4.5 µg/Inhalation, Two Inhalations Twice Daily Plus As-needed Compared With Seretide™ Diskus™ 50/500 µg/Inhalation, One Inhalation Twice Daily Plus Terbutaline Turbuhaler 0.4 mg/Inhalation As-needed - a 6- [NCT00242775] | Phase 3 | 2,100 participants | Interventional | 2005-05-31 | Completed | ||
| A Multi-Center, Randomized, Double-Blind, Parallel-Group, Dose-Finding Trial to Evaluate the Safety and Efficacy of Fluticasone Propionate Combined With Formoterol Fumarate in Patients With Chronic Obstructive Pulmonary Disease [NCT00403286] | Phase 2 | 457 participants (Actual) | Interventional | 2006-11-30 | Completed | ||
| A Phase 2, Randomized, Blinded, 5-period Cross-over, Placebo and Active Controlled, Multicenter, Dose-finding Study Comparing Single Doses of Formoterol 2.25 µg, 4.5 µg, and 9 µg Delivered Via Symbicort pMDI and Foradil® 12 µg Evaluating the Relative Bron [NCT01136655] | Phase 2 | 54 participants (Actual) | Interventional | 2010-09-30 | Completed | ||
| [NCT00462540] | Phase 3 | 100 participants (Anticipated) | Interventional | 2007-05-31 | Completed | ||
| [NCT00476073] | Phase 3 | 228 participants (Actual) | Interventional | 2007-04-30 | Completed | ||
| Prospective, Randomised, Open-label, Multicentre, Active Drug Controlled, Parallel Group Design Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate 400 mcg + Formoterol 24 mcg pMDI Via HFA-134a (Foster™) vs. Fluticasone Propionate 500 [NCT00497237] | Phase 3 | 382 participants (Anticipated) | Interventional | 2007-04-30 | Completed | ||
| A Phase I, Randomized, Double-blind, Single-dose, Partial Replicate, 3-way Cross-over Study to Assess the Lung Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI HFO Compared With BGF MDI HFA [NCT05477108] | Phase 1 | 108 participants (Actual) | Interventional | 2022-07-29 | Completed | ||
| A 12-Week, Randomized, Open-Label, Parallel-Group Study to Evaluate the Mastery of Inhaler Technique for Budesonide Formoterol (BF) SPIROMAX® (160/4.5 and 320/9 mcg) as Compared With SYMBICORT® TURBOHALER® (200/6 and 400/12 mcg) as Treatment for Adult Pat [NCT02062463] | Phase 3 | 485 participants (Actual) | Interventional | 2014-05-28 | Completed | ||
| A Double-Blind, Double-Dummy, Randomized, Placebo- and Active-Controlled, Multicenter, Parallel-Group Study of (R,R)-Formoterol in the Treatment of Subjects With Chronic Obstructive Pulmonary Disease [NCT00064402] | Phase 3 | 741 participants (Actual) | Interventional | 2002-04-30 | Completed | ||
| DOUBLE BLIND, MULTINATIONAL, MULTICENTRE, PARALLEL-GROUP DESIGN CLINICAL TRIAL OF THE EFFICACY AND TOLERABILITY OF CHF 1535 (BECLOMETHASONE DIPROPIONATE 100 µg + FORMOTEROL 6 µg) pMDI VIA HFA-134a vs. FLUTICASONE 125 µg + SALMETEROL 25 µg pMDI (SERETIDE®) [NCT00394368] | Phase 3 | 180 participants | Interventional | 2004-11-30 | Completed | ||
| A 12-Month Double-Blind, Double-Dummy, Randomized, Parallel Group, Multicenter Efficacy and Safety Study of Symbicort® pMDI 2 x 160/4.5 μg Bid and 2 x 80/4.5 μg Bid Compared to Formoterol Turbuhaler® 2 x 4.5 μg Bid and Placebo in Patients With COPD [NCT00206167] | Phase 3 | 1,600 participants | Interventional | 2005-04-30 | Completed | ||
| [NCT00215371] | Phase 2 | 32 participants | Interventional | 2002-07-31 | Completed | ||
| [NCT00215410] | Phase 2 | 36 participants | Interventional | Completed | |||
| [NCT00215449] | Phase 3 | 690 participants | Interventional | Completed | |||
| A Randomised, Double-blind, Placebo-controlled Trial Assessing the Efficacy of SLITone in House Dust Mite Allergic Patients [NCT00633919] | Phase 2/Phase 3 | 124 participants (Actual) | Interventional | 2006-07-31 | Completed | ||
| Assessment of Bronchodilator Efficacy of Formoterol/Budesonide 12/400 mcg Via Discair in Chronic Obstructive Pulmonary Disease (COPD) [NCT03028701] | Phase 4 | 33 participants (Actual) | Interventional | 2015-09-30 | Completed | ||
| A Randomised, Placebo-controlled, Double-blind (Double-dummy Technique),Crossover, Multi-centre Study, to Evaluate Onset of Effect in Patients With Chronic Obstructive Pulmonary Disease (COPD) Treated With Formoterol Turbuhaler® 9 μg, Compared With Sereve [NCT01048333] | Phase 2 | 109 participants (Actual) | Interventional | 2010-01-31 | Completed | ||
| An Open Phase III, Multi-centre 52-week, Parallel-group Study Evaluating the Safety and Efficacy of Formoterol 18 μg Daily Dose Compared With Standard COPD Treatment, in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD) [NCT01047553] | Phase 3 | 251 participants (Actual) | Interventional | 2009-12-31 | Completed | ||
| Evaluation of Changes in Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Budesonide/Formoterol (Symbicort®) Compared With Placebo [NCT01760304] | Phase 4 | 5 participants (Actual) | Interventional | 2012-01-31 | Terminated(stopped due to Sponsor decided to stop the study due to expiration of blinded placebo .) | ||
| A Randomized, Double-Dummy, Crossover, Single-Center Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers in the Treatment of Patients Recovering From Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) [NCT02291016] | 7 participants (Actual) | Interventional | 2015-02-28 | Completed | |||
| A Phase III, 52-week, Multinational, Multicenter, Randomized, Double-blind, 2-arm Parallel Group Study Comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrro [NCT04320342] | Phase 3 | 2,934 participants (Anticipated) | Interventional | 2022-04-28 | Recruiting | ||
| Double Blind, Double Dummy, Multinational, Multicentre, Parallel-Group Design Clinical Trial of the Efficacy and Tolerability of CHF 1535 (Beclomethasone Dipropionate 100 µg + Formoterol 6 µg) pMDI Via HFA-134a Vs. Budesonide 160 µg + Formoterol 4,5 µg Dr [NCT00413387] | Phase 3 | 219 participants (Actual) | Interventional | 2004-09-30 | Completed | ||
| Effects of Symbicort Single Inhaler Therapy on Bronchial Hyper Responsiveness, Asthma Control and Safety in Mild to Moderate Asthmatics in General Practice, Compared to Usual Care Therapy [NCT00235911] | Phase 3 | 100 participants | Interventional | 2003-09-30 | Completed | ||
| A Randomised, Double Blind, Double Dummy, Multicentre Phase III Study Comparing the Efficacy of Budesonide/Formoterol (Symbicort® Forte Turbuhaler®) and Oral Prednisolone + Formoterol (Oxis® Turbuhaler) During Two Weeks, in COPD Patients With an Acute Exa [NCT00259779] | Phase 3 | 120 participants (Anticipated) | Interventional | 2005-09-30 | Completed | ||
| A Comparison of Symbicort® Single Inhaler Therapy (Symbicort® 200 Turbuhaler® 1 Inhalation b.i.d. Plus as Needed) & Conventional Best Practice for the Treatment of Persistent Asthma in Adolescents & Adults-a 26-Week, Randomised, Open-Label, Parallel Group [NCT00238784] | Phase 3 | 1,300 participants | Interventional | 2004-05-31 | Completed | ||
| A Comparison of the Efficacy of Symbicort® Single Inhaler Therapy (Symbicort Turbuhaler® 160/4.5 mg 1 Inhalation b.i.d. Plus As-needed) and Conventional Best Standard Treatment for the Treatment of Persistent Asthma in Adolescents and Adults. A Randomized [NCT00242411] | Phase 4 | 1,900 participants | Interventional | 2004-09-30 | Completed | ||
| A 12-week Double-Blind, Parallel-Group, Placebo- and Active- Controlled Trial to Evaluate the Efficacy and Safety of Formoterol Fumarate Inhalation Solution 20 Mcg/0.5 mL Delivered by OMRON MicroAir NE-U22V Nebulizer in the Treatment of Patients With Chro [NCT00280371] | Phase 3 | 345 participants | Interventional | 2006-01-31 | Completed | ||
| An 8-week, Randomised, Double Blind, Parallel-group, Multi-centre, Phase III Study Comparing the Efficacy and Safety of Symbicort® Turbuhaler® 160/4.5 µg Twice Daily and Pulmicort® Turbuhaler® 200 µg Twice Daily + Theolong® Tablet 200 mg Twice Daily in Ja [NCT00252785] | Phase 3 | 340 participants | Interventional | 2005-10-31 | Completed | ||
| A Comparison of the Efficacy of Symbicort® Single Inhaler Therapy (Symbicort Turbuhaler® 160/4.5 mg 1 Inhalation b.i.d. Plus As-needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adolescents and Adults - a 26 Weeks, Randomise [NCT00252824] | Phase 3 | 1,000 participants (Anticipated) | Interventional | 2005-07-31 | Completed | ||
| A Comparison of Symbicort Single Inhaler Therapy (Symbicort Turbuhaler 160/4.5 µg, 1 Inhalation b.i.d. Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adults - a 26-Week, Randomised, Open-Label, Parallel-Group, Mul [NCT00252863] | Phase 3 | 1,600 participants | Interventional | 2004-12-31 | Completed | ||
| Effect of Symbicort on Sleep Quality in Patients With Emphysema [NCT01602523] | Phase 3 | 40 participants (Anticipated) | Interventional | 2011-03-31 | Active, not recruiting | ||
| Symbicort and Health Economics in a Real Life Evaluation - SHARE - A Randomised, Open-Label, Parallel-Group, Multicentre Study to Assess the Asthma-Related Health-Care Costs, in Ordinary Clinical Practice During 12 Months [NCT00259766] | Phase 3 | 1,970 participants | Interventional | 2004-04-30 | Completed | ||
| A Randomized Double Blind Comparison Between Single Doses of Symbicort Turbuhaler (Budesonide/Formoterol Combination), Formoterol, Salbutamol and Placebo in Repeated AMP-challenges in Patients With Mild - to Moderate Asthma. Investigating the Supplementar [NCT00272753] | Phase 4 | 20 participants | Interventional | 2004-04-30 | Completed | ||
| [NCT00280358] | Phase 1 | 30 participants | Interventional | Completed | |||
| Observational Study to Evaluate the Clinical Efficacy and Improved Quality of Life With the Administration of the Fixed Combination of Budesonide Formoterol, in Approximately 2000 Patients With Asthma [NCT03033758] | 980 participants (Actual) | Observational | 2017-02-02 | Completed | |||
| A Comparison of Symbicort Single Inhaler Therapy (Symbicort Turbohaler 160/4.5 μg, 1 Inhalation b.i.d. Plus as Needed) and Conventional Best Practice for the Treatment of Persistent Asthma in Adolescents and Adults - a 26-week, Randomised, Open-label, Par [NCT00290264] | Phase 3 | 1,000 participants | Interventional | 2004-12-31 | Completed | ||
| A Randomized, Single Dose, 3-Period Crossover Study to Evaluate the Dosage Form Proportionality, Dose Proportionality and Pharmacokinetics of Mometasone Furoate and Formoterol Fumarate From Three Combination MDI Formulations [NCT00418509] | Phase 1 | 24 participants | Interventional | 2006-11-30 | Completed | ||
| A 6-Month, Phase IIIA, Multi-Center,Randomised,Double-Blind, Double-Dummy, Parallel-Group Study of the Efficacy and Safety of Symbicort® Turbuhaler®+ Bricasol® pMDI Compared With Pulmicort® Turbuhaler®+Bricasol® pMDI in Chinese Patients With COPD [NCT00421122] | Phase 3 | 315 participants (Actual) | Interventional | 2006-09-30 | Completed | ||
| Pharmacokinetic Study Comparing Budesonide/Formoterol Easyhaler and Symbicort Turbuhaler Forte; a Randomised, Double-blind, Double-dummy, Single Centre, Single Dose, Crossover Study in Healthy Subjects [NCT01627158] | Phase 1 | 72 participants (Actual) | Interventional | 2012-06-30 | Completed | ||
| OPEN-LABEL, PROSPECTIVE EXPLORATORY STUDY TO ASSESS THE EFFECTS OF FORMOTEROL AND BECLOMETASONE DIPROPIONATE COMBINATION THERAPY USING A DPI DEVICE ON CENTRAL AND PERIPHERAL AIRWAY DIMENSIONS IN ASTHMATIC PATIENTS. [NCT01650441] | Phase 2 | 31 participants (Actual) | Interventional | 2012-04-30 | Completed | ||
| Evaluation of Effects of Chronic Dose Exposure to Cardioselective and Non-cardioselective Beta Blockers on Measures of Cardiopulmonary Function in Moderate to Severe COPD. [NCT01656005] | Phase 4 | 18 participants (Actual) | Interventional | 2012-08-31 | Completed | ||
| A SINGLE CENTRE, RANDOMISED, DOUBLE-BLIND, DOUBLE-DUMMY, 2-WAY CROSS OVER STUDY TO COMPARE SAFETY ASSESSED BY KNEMOMETRY AND URINARY CORTISOL MEASUREMENTS OF CHF1535 50/6 NEXThaler® (FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE AND FORMOTEROL FUMARATE [NCT01658891] | Phase 3 | 0 participants (Actual) | Interventional | 2014-02-28 | Withdrawn | ||
| Pharmacokinetic Study on Budesonide/Formoterol Device-metered Dry Powder Inhalers, Two Batches of Symbicort Turbuhaler and Budesonide/Formoterol Easyhaler: Randomised, Double-blind, Double-dummy, Single Centre, Single Dose, Crossover Study in Healthy Subj [NCT01668121] | Phase 1 | 48 participants (Actual) | Interventional | 2012-08-31 | Completed | ||
| Evaluation of the Efficacy and Safety of a Fixed-dose, Single-capsule Budesonide-formoterol Combination in Uncontrolled Asthma:a Randomized, Double-blind, Multicenter, Controlled Clinical Trial. [NCT01676987] | Phase 3 | 181 participants (Actual) | Interventional | 2009-04-30 | Completed | ||
| Double Blind Placebo Controlled Trial Checking the Safety and Efficacy of the Inspiromatic Inhaler in Comparison to the Aerolizer Inhaler When Delivering Formoterol [NCT01711086] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2012-10-31 | Not yet recruiting | ||
| A Phase II, Monocentric, Open, Randomized, 6-way Cross-over Clinical Pharmacology Study to Evaluate the Lung Bioavailability of BDP/B17MP and Formoterol and the Total Systemic Exposure Across Two Different Strengths of CHF 1535 NEXThaler Dry Powder Inhale [NCT01738087] | Phase 2 | 30 participants (Actual) | Interventional | 2012-11-30 | Completed | ||
| The Effects of Atorvastatin Treatment in COPD Patients [NCT01748279] | Phase 4 | 18 participants (Actual) | Interventional | 2012-12-31 | Completed | ||
| The Role of Theophylline Plus Low-dose Formoterol-budesonide in Treatment of Bronchiectasis [NCT01769898] | Phase 4 | 50 participants (Actual) | Interventional | 2013-07-31 | Completed | ||
| Polymorphism of beta2-adrenoceptor and Regular Use of Formoterol in Asthma: Preliminary Results [NCT01786616] | 30 participants (Actual) | Observational | 2005-01-31 | Completed | |||
| A SINGLE-DOSE, OPEN LABEL, RANDOMIZED, 3-WAY CROSSOVER, CLINICAL PHARMACOLOGY STUDY OF CHF 1535 100/6 pMDI (FIXED COMBINATION OF BECLOMETHASONE DIPROPIONATE 100 µg PLUS FORMOTEROL FUMARATE 6 µg) WITH OR WITHOUT SPACER DEVICE VERSUS THE FREE COMBINATION OF [NCT01803087] | Phase 2 | 60 participants (Actual) | Interventional | 2012-02-29 | Completed | ||
| A Randomized, Double-blind, Active-controlled, Parallel Group, Stratified, Multi-center, 12-week Study Comparing the Safety & Efficacy of Fluticasone and Formoterol Combination (FlutiForm(tm) 100/10 µg Twice Daily) in a Single Inhaler (SkyePharma HFA pMDI [NCT00394199] | Phase 3 | 357 participants (Actual) | Interventional | 2006-06-30 | Completed | ||
| Long-term Open-label Safety Study With SkyePharma FlutiForm HFA pMDI (100/10 µg and 250/10 µg) in Adult and Adolescent Patients With Asthma [NCT00394121] | Phase 3 | 400 participants (Anticipated) | Interventional | 2006-03-31 | Completed | ||
| Comparison of Bronchodilator Efficacy of Tiotropium/Formoterol Combination Treatment Administered (qd) Via Discair® With Tiotropium (qd) Monotherapy or Tiotropium (qd) + Formoterol (Bid) Free Combination Treatment in Patients With Chronic Obstructive Pulm [NCT02988869] | Phase 4 | 84 participants (Actual) | Interventional | 2016-08-31 | Completed | ||
| A 24-week Treatment, Randomised, Parallel-group, Double Blinded, Double-Dummy, Multicenter Study to Assess the Efficacy and Safety of Aclidinium Bromide/Formoterol Fumarate Compared With Individual Components and Placebo and Aclidinium Bromide Compared Wi [NCT03022097] | Phase 3 | 1,067 participants (Actual) | Interventional | 2017-01-24 | Completed | ||
| A 1-year Multi-center, Prospective, Cohort Study in Patients With Chronic Obstructive Pulmonary Disease Treated With Long-acting Bronchodilator [NCT01794780] | Phase 4 | 2,229 participants (Actual) | Interventional | 2013-02-05 | Completed | ||
| A Long-Term, Randomized, Study of the Safety and Tolerability of a Fixed-Dose Combination of Aclidinium Bromide/Formoterol Fumarate Compared With Formoterol Fumarate in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD) [NCT01437540] | Phase 3 | 590 participants (Actual) | Interventional | 2011-09-19 | Completed | ||
| Open Label, Uncontrolled, Non-randomized, Single Dose, Scintigraphic Study to Investigate Lung Deposition of Inhaled 99mTc Radiolabelled CHF5993 pMDI in Healthy Volunteers, Asthmatic and COPD Patients [NCT02975843] | Phase 1 | 28 participants (Actual) | Interventional | 2016-11-21 | Completed | ||
| Replication of the P04334 Asthma Trial in Healthcare Claims Data [NCT04892758] | 10,288 participants (Actual) | Observational | 2020-10-29 | Completed | |||
| Replication of the D58 Asthma Trial in Healthcare Claims Data [NCT04892732] | 66,581 participants (Actual) | Observational | 2020-10-29 | Completed | |||
| Comparison of the Efficacy and Safety of Budesonide/Formoterol Turbuhaler® Versus Terbutaline Nebulization as Reliever Therapy in Children With Asthma Presenting at the Emergency Room for Moderate Exacerbation [NCT04705727] | Phase 3 | 102 participants (Actual) | Interventional | 2021-08-23 | Terminated(stopped due to Not enough recruitment in th trial) | ||
| Randomized Double-blind Placebo-controlled Crossover Study to Evaluate the Effects of Formoterol and Beclomethasone Dipropionate Combination Therapy on Small Airways Function in COPD Patients. [NCT01466712] | Phase 4 | 20 participants (Anticipated) | Interventional | 2011-11-30 | Enrolling by invitation | ||
| A Single-dose,Open-label,Randomized,2-way Cross-over,Clinical Pharmacology Study of CHF1535 50/6 NEXT DPI® Fixed Combination of Beclomethasone Dipropionate 50µg Plus Formoterol Fumarate 6µg)Versus the Free Combination of Licensed Beclomethasone DPI and Fo [NCT01468272] | Phase 2 | 26 participants (Actual) | Interventional | 2011-11-30 | Completed | ||
| A Phase I, Randomized, Double-Blind, Single-Dose, Four-Period, Four-Treatment, Cross-Over Study Evaluating the Safety and Pharmacokinetics of Two Doses of PT003 and Two Doses of PT001 in Japanese Healthy Subjects [NCT02196714] | Phase 1 | 24 participants (Actual) | Interventional | 2014-07-31 | Completed | ||
| A 2-Week Double-Blind, Placebo-Controlled, Parallel Group Study Comparing the Anti-Inflammatory Effects of Low, Medium, and High Dose Mometasone Furoate/Formoterol Fumarate MDI Formulation and Medium Dose Mometasone Furoate DPI and MDI Formulations in Adu [NCT00635882] | Phase 2 | 93 participants (Actual) | Interventional | 2008-02-29 | Completed | ||
| A Randomized, Multiple-Dose, Crossover Study Characterizing the Pharmacodynamic Profiles of Formoterol Fumarate Inhalation Solution and Formoterol Dry Powder Inhaler in Subjects With Stable Chronic Obstructive Pulmonary Disease [NCT01113593] | Phase 2 | 45 participants (Actual) | Interventional | 2010-05-31 | Completed | ||
| Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease [NCT04331470] | Phase 2/Phase 3 | 30 participants (Anticipated) | Interventional | 2020-04-04 | Recruiting | ||
| A 24-week Randomised Exploratory Open-Label Study Aiming To Characterise Changes In Airway Inflammation, Symptoms, Lung Function, And Reliever Use In Asthma Patients Using SABA (Salbutamol) Or Anti-Inflammatory Reliever (SYMBICORT®) As Rescue Medication I [NCT03924635] | Phase 4 | 40 participants (Actual) | Interventional | 2019-08-01 | Completed | ||
| Randomized, Single Blind, Parallel Group, Placebo Controlled, Multidose Study Comparing the Therapeutic Equivalence of a 3M Budesonide/Formoterol Fumarate Inhaler and a Symbicort® Reference Inhaler in Adult Subjects With Asthma [NCT03015259] | Phase 3 | 1,762 participants (Actual) | Interventional | 2016-12-29 | Completed | ||
| Open Randomized Low Interventional Clinical Trial to Compare Efficiency in Control Symptoms Between Fluticasone Propionate/Formoterol K-haler (Medium Strength) vs High Strength ICS/LABA in the Treatment of Patients With Persistent Asthma [NCT04271839] | Phase 4 | 0 participants (Actual) | Interventional | 2020-06-11 | Withdrawn(stopped due to The trial has been terminated early due to the SARS-CoV-2 pandemic.) | ||
| A Pilot Study to Determine the Most Effective Dose of Arformoterol for Treating Acute Asthmatic Patients Presenting to the Emergency Department and to Evaluate Its Side Effect and Safety Profile When Used in This Clinical Situation. [NCT00819637] | Phase 4 | 2 participants (Actual) | Interventional | 2009-01-31 | Terminated(stopped due to Unable to enroll r/t study design & staffing issues. The trial terminated.) | ||
| Efficacy of Inhaling Bronchodilator Medications in Patients With Chronic Obstructive Pulmonary Disease Who Have a Low Peak Inspiratory Flow Rate [NCT01391559] | 20 participants (Actual) | Interventional | 2011-07-31 | Completed | |||
| A 26-Week Randomized, Double-Blinded, Active Controlled Study Comparing the Safety of Mometasone Furoate/Formoterol Fumarate MDI Fixed Dose Combination Versus Mometasone Furoate MDI Monotherapy in Adolescents and Adults With Persistent Asthma (Protocol No [NCT01471340] | Phase 4 | 11,744 participants (Actual) | Interventional | 2012-01-09 | Completed | ||
| A Randomised, Placebo-Controlled, Double-Blind, Multi-Centre, 4-week, 3-way Crossover Pharmacodynamic Study to Assess the Equivalence of Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF) Delivered by MDI HFO Compared With BGF Delivered by MDI HFA [NCT06075095] | Phase 3 | 240 participants (Anticipated) | Interventional | 2024-01-15 | Not yet recruiting | ||
| Effect of Symbicort on GR (Glucocorticoid Receptor) Translocation in Induced Sputum in Comparison With Budesonide, Formoterol and Placebo. A Single Dose Exploratory Study in Patients With Mild Asthma [NCT00159263] | 10 participants (Actual) | Interventional | 2004-11-30 | Completed | |||
| An Open-Label Study to Assess the Safety and Tolerability of Zenhale® (a Fixed-Dose Combination of Mometasone Furoate/Formoterol Fumarate Delivered by Metered Dose Inhaler) in 40 Subjects With Persistent Asthma (Protocol No. 206-00 [P08212]) [NCT01566149] | Phase 3 | 49 participants (Actual) | Interventional | 2012-03-31 | Completed | ||
| A 3-week Multicenter Study Investigating Patient Use and Functionality of Formoterol in a Novel Inhalation Device in Patients With Asthma [NCT00130351] | Phase 3 | 155 participants (Actual) | Interventional | 2005-07-31 | Completed | ||
| Pharmacokinetic Study Comparing Two Budesonide/Formoterol Fumarate Dihydrate Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler 320/9 Microg/Inhalation and Symbicort Turbuhaler Forte; a Randomised, Double-blind, Single Centre, Single Dose [NCT01593826] | Phase 1 | 72 participants (Actual) | Interventional | 2012-05-31 | Completed | ||
| Symptom-driven ICS/LABA Therapy for Adolescent Patients With Asthma Non-adherent to Daily Maintenance Inhalers [NCT05689983] | Phase 1/Phase 2 | 40 participants (Anticipated) | Interventional | 2022-04-01 | Recruiting | ||
| Single-Centre Randomised Open Crossover Study to Examine the Influence of Different Internal Resistances of Discus and Turbohaler Respectively on the Effects of Salmeterol and Formoterol in Asthmatic Subjects [NCT00327353] | Phase 4 | 77 participants | Interventional | 2004-01-31 | Completed | ||
| A Phase III, 24 Week, Randomized, Double Blind, Double Dummy, Parallel Group Study (With an Extension to 52 Weeks in a Subset of Subjects) Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI Administered Once Da [NCT02345161] | Phase 3 | 1,811 participants (Actual) | Interventional | 2015-01-23 | Completed | ||
| A Randomized, Double-Blind (Test Products and Placebo), Chronic Dosing (24 Weeks), Placebo-Controlled, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared [NCT01854658] | Phase 3 | 1,615 participants (Actual) | Interventional | 2013-07-31 | Completed | ||
| A Randomized, Phase IIIb, Two-period, Two-treatment Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects With Moderate to Very Severe COPD After 4 Weeks of Treatment With PT003 and Placebo MDI [NCT02347085] | Phase 3 | 43 participants (Actual) | Interventional | 2015-02-01 | Completed | ||
| Blacks and Exacerbations on LABA vs. Tiotropium (BELT) [NCT01290874] | Phase 3 | 1,070 participants (Actual) | Interventional | 2011-03-30 | Completed | ||
| A Phase 4, Randomized, Double-blind, Multicenter, Placebo-Controlled Two Way Cross-Over Study to Evaluate Changes in Oxygen Consumption and Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Symbicort pMDI 160/4.5 μg. [NCT02533505] | Phase 4 | 51 participants (Actual) | Interventional | 2015-08-25 | Completed | ||
| An Open-Label, Multi-Center, Dose Indicator Study of Glycopyrronium and Formoterol Fumarate (GFF) Metered Dose Inhaler (MDI) in Adult Subjects With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) [NCT02268396] | Phase 3 | 138 participants (Actual) | Interventional | 2014-11-30 | Completed | ||
| SHAMAL: A Multicentre, Randomised, Open-Label, Parallel-Group, Active-Controlled, Phase IV Study to Assess the Reduction of Daily Maintenance ICS/LABA Treatment Towards Anti-Inflammatory Reliever Treatment in Patients With Severe Eosinophilic Asthma Treat [NCT04159519] | Phase 4 | 168 participants (Actual) | Interventional | 2020-07-27 | Completed | ||
| Non-inferiority Evaluation of Trimbow in Critically Ill Patients Admitted in ICU Compared to Standard of Care [NCT04737655] | Phase 4 | 200 participants (Anticipated) | Interventional | 2021-02-15 | Not yet recruiting | ||
| Open Label, Uncontrolled, Non-randomized, Single Dose, Scintigraphic Study to Investigate Lung Deposition of Inhaled 99mTc Radiolabelled TRIMBOW® pMDI in Healthy Volunteers, Asthmatic and COPD Patients [NCT03795350] | Phase 1 | 19 participants (Actual) | Interventional | 2019-01-14 | Terminated(stopped due to In light of the cessation of non-essential clinical activities at CPU due to the COVID-19 pandemic, the sponsor has determined to terminate the study early.) | ||
| Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers [NCT01225913] | Phase 4 | 50 participants (Anticipated) | Interventional | 2007-10-31 | Recruiting | ||
| Evaluation of Mechanism(s)Limiting Expiratory Airflow in Chronic, Stable Asthmatics Who Are Non-smokers [NCT00576069] | 60 participants (Anticipated) | Observational | 2007-10-25 | Recruiting | |||
| A 4-week, Open-label, Randomized, Multi-centre, Parallel-group Study Evaluating the Safety and Efficacy of 4 Actuations Symbicort® (Budesonide/Formoterol) HFA pMDI 40/2.25 μg Twice Daily, With and Without Spacer, in Children (6-11 Years) With Asthma [NCT00536913] | Phase 3 | 107 participants (Actual) | Interventional | 2007-09-30 | Completed | ||
| Observation of the Respiratory Impedance and Inflammation in Cough Variant Asthma Patients Treated in Combination of Chanqin Granules. [NCT03319043] | Phase 1/Phase 2 | 120 participants (Anticipated) | Interventional | 2017-11-01 | Not yet recruiting | ||
| Efficiency of Twice Daily Formoterol Versus Once Daily Tiotropium in Patients With GOLD A/B COPD: a Randomised, Open-label, Multicentre Trial [NCT03258749] | 120 participants (Anticipated) | Interventional | 2017-11-01 | Not yet recruiting | |||
| Effect of Aclidinium Bromide/Formoterol on Nighttime Lung Function, Respiratory Mechanics and Early Morning Symptoms in Chronic Obstructive Pulmonary Disease (COPD) [NCT02429765] | Phase 4 | 40 participants (Actual) | Interventional | 2015-10-31 | Completed | ||
| Effect of Inhaled Mometasone/Formoterol Versus Inhaled Fluticasone/Salmeterol on Peripheral Airway Function in Asthma Patients [NCT02415179] | 52 participants (Actual) | Interventional | 2015-05-31 | Completed | |||
| A Randomised, Open-label, 2-group PK (3-period) and PD (5-period) Crossover Study to Compare Systemic Exposure and Pharmacodynamic Effects of Fluticasone/Formoterol BAI and pMDI in Healthy Volunteers [NCT02403713] | Phase 1 | 125 participants (Anticipated) | Interventional | 2014-08-31 | Completed | ||
| Extra-fine Formoterol/Beclomethasone in the Treatment of Asthmatic Crisis [NCT02345993] | Phase 4 | 120 participants (Anticipated) | Interventional | 2015-01-31 | Active, not recruiting | ||
| A Guideline Approach to Therapy Step-down Utilising Flutiform Change and Step-down [NCT02388373] | Phase 4 | 225 participants (Actual) | Interventional | 2014-07-31 | Completed | ||
| A Phase 3b, 42-day, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Safety and Tolerability of Nebulized Revefenacin and Nebulized Formoterol Fumarate (PERFOROMIST®) Administered in Sequence and as a Combined Solution in [NCT03573817] | Phase 3 | 122 participants (Actual) | Interventional | 2018-05-31 | Completed | ||
| A 26-week Treatment, Multicenter, Randomized, Parallel Group, Blinded Study to Assess the Efficacy and Safety of QVA149 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease Using Tiotropium Plus Formoterol as Control [NCT01574651] | Phase 3 | 934 participants (Actual) | Interventional | 2012-05-31 | Completed | ||
| A Phase III, Randomized, Double-blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo fo [NCT01437397] | Phase 3 | 1,692 participants (Actual) | Interventional | 2011-09-30 | Completed | ||
| Efficacy and Safety Study of Two Fixed-Dose Combinations of Aclidinium Bromide With Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate, and Placebo All Administered Twice Daily (BID) to Patients With Stable, Moderate to Severe Chron [NCT01049360] | Phase 2 | 128 participants (Actual) | Interventional | 2009-12-31 | Completed | ||
| Pharmacokinetic Pilot Study on Budesonide/Formoterol Device-metered Dry Powder Inhalers, Budesonide/Formoterol Easyhaler and Symbicort Turbuhaler: A Randomised, Open, Single Centre, Single Dose, Crossover Study in Healthy Subjects [NCT01457716] | 17 participants (Actual) | Interventional | 2011-10-31 | Completed | |||
| A Single Centre, Randomised, Double-blind, Double-dummy, 2-way Cross Over Study to Compare Safety Assessed by Knemometry and Urinary Cortisol Measurements of CHF1535 50/6 Pmdi (Fixed Combination of Beclomethasone Dipropionate and Formoterol Fumarate) and [NCT01450774] | Phase 3 | 72 participants (Actual) | Interventional | 2011-09-30 | Completed | ||
| Multicenter Randomized Parallel-Group 6-Week Treatment Clinical Study to Assess BE of Budesonide 80 μg and Formoterol Fumarate Dihydrate 4.5 μg Inhalation Product in Comparison With Reference Product, Symbicort® in Adult Asthma Patients [NCT05322707] | Phase 3 | 1,485 participants (Actual) | Interventional | 2022-04-15 | Completed | ||
| A 26 Week, Randomized, Active-controlled Safety Study of Double-blind Formoterol Fumarate in Free Combination With an Inhaled Corticosteroid Versus an Inhaled Corticosteroid in Adolescent and Adult Patients With Persistent Asthma. [NCT01845025] | Phase 4 | 827 participants (Actual) | Interventional | 2013-05-31 | Terminated(stopped due to Due to the action to withdraw the Foradil Aerolizer NDA in US; study was discontinued. This was a commercial reason and not due to any change in benefit-risk.) | ||
| Effects of Arformoterol on Exercise Endurance Time and Breathlessness in COPD: Cycle Ergometer vs. Treadmill [NCT00754546] | Phase 4 | 20 participants (Actual) | Interventional | 2008-08-31 | Completed | ||
| Relative Potency of Formoterol Novolizer® 12 µg Compared to Formoterol Aerolizer® 12 µg in Patients With Stable Asthma Using Bronchoprovocation With Methacholine as a Bioassay Randomized, Double-blind, Four-period, Four-sequence Cross-over Trial [NCT01256086] | Phase 2 | 44 participants (Actual) | Interventional | 2010-12-31 | Completed | ||
| Comparison of Conventional Medicine, TCM Treatment and Combination of Both Conventional Medicine and TCM Treatment for Patients With Chronic Obstructive Pulmonary Disease: A Randomized Comparative Effectiveness Research Trial [NCT01836016] | Phase 3 | 360 participants (Anticipated) | Interventional | 2013-05-31 | Not yet recruiting | ||
| Lung Function Changes Following the Addition of Formoterol Inhalation Capsules (12 µ Once or Twice Daily) to Pharmacodynamic Steady State of Once Daily Tiotropium (18 µg) Inhalation Capsule in Patients With COPD [NCT02242240] | Phase 2 | 95 participants (Actual) | Interventional | 2001-03-31 | Completed | ||
| A Real Life, on International, Multicenter Study to Assess the Efficacy and Quality of Life in Greek Asthmatic Patients Who Will be on Fixed Dose Bodesonide Formoterol Combination Treatment [NCT03055793] | 1,400 participants (Actual) | Observational | 2017-03-01 | Completed | |||
| A 12-Week Efficacy and Safety Evaluation of Budesonide/Formoterol SPIROMAX(R) 160/4.5 mcg Inhalation Powder Versus SYMBICORT(R) TURBOHALER(R) 200/6 mcg in Adult and Adolescent Patients With Persistent Asthma [NCT01803555] | Phase 3 | 605 participants (Actual) | Interventional | 2013-07-04 | Completed | ||
| Pharmacokinetic Pilot Study Comparing Three Formulations of Budesonide/Formoterol Easyhaler 160/4.5 Microg/Inhalation and Symbicort Turbuhaler: A Randomised, Open, Single Centre, Single Dose, Crossover Study in Healthy Subjects [NCT03073057] | Phase 1 | 20 participants (Actual) | Interventional | 2016-01-31 | Completed | ||
| Multicentric, Open-label, Randomized, Parallel--group Study to Evaluate the Efficacy and Safety of Omalizumab in a 12- Month Period, in Patients With Severe IgE-mediated Asthma Inadequately Controlled With High Doses of Corticosteroids. [NCT01912872] | Phase 4 | 112 participants (Actual) | Interventional | 2013-11-11 | Terminated(stopped due to Termination was due to identified errors in data management handling after an internal audit by the sponsor performed by third party.) | ||
| The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and Dyspnea is Associated to the Improvement in Small Airway Dysfunction in COPD Patients. A Pilot Study (IOSCOPD20161102) [NCT04421742] | 43 participants (Actual) | Observational | 2017-05-31 | Completed | |||
| A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety of Long-Term Use of Perforomist® (Formoterol Fumarate) Inhalation Solution in Subjects With Chronic Obstructive Pulmonary Disease (COPD) [NCT01488019] | Phase 4 | 1,071 participants (Actual) | Interventional | 2012-03-31 | Completed | ||
| The Effect of the Beta 2 Agonist, Formoterol, on Recovery From Hypoglycemia [NCT01194479] | 14 participants (Actual) | Interventional | 2010-08-31 | Completed | |||
| A Double-Blind, Crossover Study to Assess the Effects of Nebulized Brovana Added to Tiotropium on FEV1, Hyperinflation, and Exercise Endurance Capacity in COPD [NCT00773786] | Phase 4 | 20 participants (Actual) | Interventional | 2008-10-31 | Completed | ||
| A Randomised, Double-blind, Double-dummy, Active-controlled Study Evaluating the Efficacy, Safety and Tolerability of Twice-daily Aclidinium Bromide/Formoterol Fumarate Compared With Twice-daily Salmeterol/Fluticasone Propionate for 24 Weeks Treatment in [NCT01908140] | Phase 3 | 933 participants (Actual) | Interventional | 2013-09-30 | Completed | ||
| Efficacy and Tolerability Study of Symbicort Turbuhaler(160/4.5µg/Inhalation,2inhalations Twice Daily) Added to Atrovent (20µg/Inhalation, 2 Inhalations 4 Times Daily)+Theophylline SR(0.1g/Tablet,1 Tablet p.o. Twice Daily) Compared With Atrovent+Theophyll [NCT01415518] | Phase 4 | 581 participants (Actual) | Interventional | 2011-09-01 | Completed | ||
| GR Activity in Induced Sputum Macrophages, and a Change in Inflammatory Biomarkers 2-hours After a Single Dose of Either Symbicort®/Budesonide/Formoterol or in Chronic Obstructive Pulmonary Disease (COPD) [NCT01787097] | Phase 4 | 31 participants (Actual) | Interventional | 2013-01-31 | Completed | ||
| LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Agonist (Formoterol) [NCT01783821] | Phase 2 | 61 participants (Actual) | Interventional | 2013-07-31 | Completed | ||
| A Randomised, Parallel-group, Open-label, Multicentre, 3-month Phase IV, Efficacy and Tolerability Study of Budesonide/Formoterol (Symbicort® Turbuhaler® 160/4.5μg/Inhalation, 2 Inhalations Twice Daily) Added to Tiotropium (SpirivaTM 18 μg/Inhalation, 1 I [NCT01397890] | Phase 4 | 793 participants (Actual) | Interventional | 2011-07-31 | Completed | ||
| A Randomized, Double-Blind, Active-Controlled, Parallel-Group, Multicenter, 4-Week Pilot Study to Assess Symptoms in Stable, Moderate to Severe COPD Patients Taking Aclidinium Bromide 200 mcg Once Daily in Combination With Formoterol Fumarate Once or Twic [NCT00706914] | Phase 2 | 156 participants (Actual) | Interventional | 2008-06-30 | Terminated(stopped due to Actual sample size of 156 was sufficient to estimate the clinical outcomes.) | ||
| Aclidinium Bromide Drug Utilisation Post-Authorisation Safety Studies (DUS): Common Protocol for Aclidinium (DUS1) and Aclidinium/Formoterol Fixed-Dose Combination (DUS2) [NCT03333018] | 22,155 participants (Actual) | Observational | 2015-07-06 | Completed | |||
| A Randomized, Double-Blind, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT009 Compared to PT005 on COPD Exacerbations Over a 52-Week Treatment Period in Subjects With Moderate to Very Severe COPD [NCT02727660] | Phase 3 | 1,876 participants (Actual) | Interventional | 2016-04-29 | Completed | ||
| Randomized Clinical Trials to Compare Asthma Control Efficacy of the Fine-particle Combination Formoterol/Beclomethasone by pMDI Administered With and Without Spacer. [NCT01453881] | Phase 3 | 45 participants (Actual) | Interventional | 2011-04-30 | Completed | ||
| Randomised Controlled Single and Chronic Dosing Crossover Comparison of Extra Fine Particle Formoterol and Coarse Particle Salmeterol in Asthmatic Patients With Persistent Small Airways Dysfunction [NCT01892787] | Phase 4 | 17 participants (Actual) | Interventional | 2013-07-31 | Completed | ||
| A Phase III, Long-term, Randomized, Double-blind, Extension Study of the Efficacy, Safety, and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate, Aclidinium Bromide, Formoterol Fumarate and Placebo for 28- Weeks Treatme [NCT01572792] | Phase 3 | 921 participants (Actual) | Interventional | 2012-04-30 | Completed | ||
| Impact of Inhaled PT003 on Complexity and Variability of Tidal Breathing and Oscillatory Mechanics in Stable COPD Patient [NCT04087590] | Phase 2 | 35 participants (Anticipated) | Interventional | 2020-01-14 | Recruiting | ||
| A Pilot Study of Efficacy of As-needed Budesonide/Formoterol Turbuhaler During Stepping Down Period From Step-3 in Adult Patients With Adequately Controlled Asthma [NCT04215848] | Phase 3 | 31 participants (Actual) | Interventional | 2020-04-01 | Completed | ||
| A Randomized, Multiple-Dose,Double-Blind,Crossover Trial to Assess the Systemic Exposure of Fluticasone Propionate (FP)/Formoterol Fumarate (FF) Fixed-Dose Combination in Subjects With Chronic Obstructive Pulmonary Disease (COPD) [NCT00774761] | Phase 2 | 97 participants (Actual) | Interventional | 2008-11-30 | Completed | ||
| A 6-month, Open Label, Randomised, Efficacy Study to Evaluate Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) Inhalation Powder Delivered Once Daily Via the Dry Powder Inhaler ELLIPTA™ Compared With Usual ICS/LABA Maintenance Therapy Delivere [NCT02446418] | Phase 3 | 423 participants (Actual) | Interventional | 2015-07-09 | Completed | ||
| ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA) [NCT04193878] | Phase 3 | 600 participants (Anticipated) | Interventional | 2020-06-01 | Recruiting | ||
| A Randomized, Blinded, Parallel Group, Placebo-Controlled, Multiple Dose, Multicenter, Multinational Study to Compare the Therapeutic Equivalence of a Budesonide 80 μg/Formoterol Fumarate Dihydrate 4.5 μg Inhalation Aerosol (Manufactured by Catalent for W [NCT02495168] | Phase 3 | 1,714 participants (Actual) | Interventional | 2017-01-13 | Completed | ||
| Randomized, Open-label, Three Arms Study to Evaluate the Efficacy of Inhaled Therapies in the Treatment of Acute Symptoms Associated With COVID-19 and in the Prevention of the Use of Health Resources in Patients With ≥ 18 Years Old (TRIVID Study) [NCT04937543] | Phase 2 | 50 participants (Actual) | Interventional | 2021-06-28 | Active, not recruiting | ||
| Multicenter, Open-label, Non-interventional Study (NIS) to Evaluate Patient's Satisfaction and Preference, the Usability of DuoResp® SPIROMAX® and the Impact on Clinical Effects, in the Daily Routine of Asthma and COPD Treatment [NCT02384577] | 4,034 participants (Actual) | Observational | 2014-07-31 | Completed | |||
| A Multiple Dose, Randomized, Double-blind, Placebo Controlled, Parallel Clinical Trial to Assess the Effect of Aclidinium Bromide/Formoterol Fumarate Fixed-dose Combination on Lung Hyperinflation, Exercise Capacity and Physical Activity in Moderate to Sev [NCT02424344] | Phase 4 | 267 participants (Actual) | Interventional | 2015-04-27 | Completed | ||
| A Randomized, Double-Blind, Chronic Dosing (24 Weeks), Placebo-Controlled, Parallel Group, Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD, Compared With Placebo [NCT02343458] | Phase 3 | 1,756 participants (Actual) | Interventional | 2015-03-30 | Completed | ||
| A Double Blind, Double Dummy, Randomised, Multicentre, Two Arm Parallel Group Study to Assess the Efficacy and Safety of FLUTIFORM® pMDI (2 Puffs Bid) vs Seretide® pMDI (2 Puffs Bid) in Subjects Aged ≥12 Years With Moderate to Severe Persistent, Reversibl [NCT03387241] | Phase 3 | 330 participants (Anticipated) | Interventional | 2017-06-02 | Recruiting | ||
| Efficacy and Safety of Aclidinium Bromide/Formoterol Fumarate Fixed-dose Combinations Compared With Individual Components and Placebo When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease. [NCT01462942] | Phase 3 | 2,443 participants (Actual) | Interventional | 2011-10-31 | Completed | ||
| A Clinical Study Comparing Symbicort 'as Needed' With Pulmicort Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma [NCT02224157] | Phase 3 | 4,215 participants (Actual) | Interventional | 2014-11-28 | Completed | ||
| A Phase IIIB, 6-Month, Double-blind, Double-dummy, Randomized, Parallel-group, Multicenter Exacerbation Study of Symbicort® Pressurized Metered-Dose Inhaler (pMDI) 160/4.5 μg x 2 Actuations Twice-daily Compared to Formoterol Turbuhaler 4.5 μg x 2 Inhalati [NCT02157935] | Phase 3 | 2,026 participants (Actual) | Interventional | 2014-06-27 | Completed | ||
| Improving Asthma Control in the Real World: A Systematic Approach to Improving Dulera Adherence [NCT02045875] | Phase 4 | 50 participants (Actual) | Interventional | 2014-03-04 | Completed | ||
| A Clinical Study Comparing Symbicort® 'as Needed' With Terbutaline 'as Needed' and With Pulmicort® Twice Daily Plus Terbutaline 'as Needed' in Adult and Adolescent Patients With Asthma. [NCT02149199] | Phase 3 | 3,850 participants (Actual) | Interventional | 2014-07-07 | Completed | ||
| A Prospective Study of Salvational Intervention With ICS/LABA for Reducing Chronic Obstructive Pulmonary Disease Exacerbation Under Severe Air Pollution (SIRCAP) in Beijing [NCT03083067] | 402 participants (Actual) | Interventional | 2017-03-20 | Completed | |||
| A 12-wk, Rand., Double-blind, Double Dummy, Multi-ctr., Phase IV Study Comparing Efficacy and Safety of SYMBICORT® pMDI 160/4.5 ug x 2 Actuations Twice Daily Versus Pulmicort® (Budesonide Inhalation Powder DPI) 180 ug x 2 Inhalations Twice Daily, in Adult [NCT00702325] | Phase 4 | 311 participants (Actual) | Interventional | 2008-06-30 | Completed | ||
| A 12 Week, Randomized, Double-blind, Multicenter, Active Controlled, 2-Arm Parallel Group Study Testing the Superiority of CHF 1535 pMDI 800/24µg Total Daily Dose (Fixed Combination of Extrafine Beclomethasone Dipropionate Plus Formoterol Fumarate) Compar [NCT05292586] | Phase 3 | 580 participants (Anticipated) | Interventional | 2022-10-05 | Recruiting | ||
| Phase II, Randomized, Placebo-controlled, Double-blind, Double-dummy, 5-period Complete Crossover Study of the Bronchodilator Effects of Formoterol Fumarate Inhalation Powder in Patients With Mild to Moderate Asthma. [NCT01641081] | Phase 2 | 174 participants (Actual) | Interventional | 2012-06-30 | Completed | ||
| Multicenter, Randomized, Double-blind, Double-dummy, National, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Flamboyant 200/12 Association in the Treatment of Adults With Severe Asthma . [NCT04191447] | Phase 3 | 134 participants (Anticipated) | Interventional | 2022-07-22 | Recruiting | ||
| A Comparative Effectiveness and Safety Study of Arformoterol Tartrate Inhalation Solution and Tiotropium Bromide on Re-hospitalization in Chronic Obstructive Pulmonary Disease (COPD) Subjects [NCT02275481] | Phase 4 | 66 participants (Actual) | Interventional | 2014-11-30 | Terminated(stopped due to lack of enrollment) | ||
| Multicenter, Randomized, Double-blind, Double-dummy, National, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Flamboyant 125/12 Association in the Treatment of Adults With Moderate Asthma . [NCT04191434] | Phase 3 | 134 participants (Anticipated) | Interventional | 2022-07-22 | Recruiting | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
The GR-GRE binding is the glucocorticoid receptor (GR) DNA binding affinity. GR-GRE activity as assed by enzyme-immunosorbent assay (NCT00159263)
Timeframe: 1-2h
| Intervention | GRE activity (OD) (Median) |
|---|---|
| Placebo | 1.4 |
| Formoterol | 1.4 |
| Budesonide Low Dose | 1.6 |
| Budesonide High Dose | 2.3 |
| Budesonide/Formoterol Combination Single | 3.5 |
| Budesonide/Formoterol Combination Double | 3 |
Changes in MKP-1 mRNA measured by PCR (NCT00159263)
Timeframe: 1-2h
| Intervention | MKP1/GNB2L1 ratio (Median) |
|---|---|
| Placebo | 1 |
| Formoterol | 3 |
| Budesonide Low Dose | 3 |
| Budesonide High Dose | 4 |
| Budesonide/Formoterol Combination Single | 5 |
| Budesonide/Formoterol Combination Double | 5 |
Measured by PCR (NCT00159263)
Timeframe: 1-2h
| Intervention | IL8/GNB2L1 ratio (Median) |
|---|---|
| Placebo | 1 |
| Formoterol | 4 |
| Budesonide Low Dose | 4 |
| Budesonide High Dose | 0.4 |
| Budesonide/Formoterol Combination Single | 0.2 |
| Budesonide/Formoterol Combination Double | 0.2 |
New Electrocardiogram (ECG) alerts are defined as those alerts that occurred post-treatment and were not present at baseline. (NCT00250679)
Timeframe: visit 6 (week 27)
| Intervention | Participants (Number) |
|---|---|
| Formoterol 12 Mcg 2x/Day | 1 |
| Arformoterol 15 Mcg 2x/Day | 1 |
| Arformoterol 25 Mcg 2x/Day | 5 |
New holter monitoring alerts are defined as those alerts that occurred post-randomization and were not present at baseline. (NCT00250679)
Timeframe: Visit 6 (week 27)
| Intervention | Participants (Number) |
|---|---|
| Formoterol 12 Mcg 2x/Day | 15 |
| Arformoterol 15 Mcg 2x/Day | 19 |
| Arformoterol 25 Mcg 2x/Day | 9 |
The 6 hour peak change from baseline is the maximum of the post-dose change values through 6 hours at each visit. (NCT00250679)
Timeframe: weeks 0,3,13,26
| Intervention | Liter (Mean) | |||
|---|---|---|---|---|
| Visit 2 (week 0) n=147,149,147 | Visit 3 (week 3) n=133,133,131 | Visit 4 (week 13) n=117,112,111 | Visit 5 (week 26) n=108,100,103 | |
| Arformoterol 15 Mcg 2x/Day | 0.314 | 0.305 | 0.316 | 0.302 |
| Arformoterol 25 Mcg 2x/Day | 0.357 | 0.334 | 0.323 | 0.343 |
| Formoterol 12 Mcg 2x/Day | 0.294 | 0.280 | 0.251 | 0.264 |
Mean change from baseline in distance walked (meters) (NCT00250679)
Timeframe: Post-Dose weeks 0, 13, 26
| Intervention | meters (Mean) | ||
|---|---|---|---|
| Visit 2 (week 0 - post dose) n=146,148,146 | Visit 4 (week 13 - post dose) n=116,110,112 | Visit 5 (week 26 - post dose) n=106,97,103 | |
| Arformoterol 15 Mcg 2x/Day | 15.72 | 4.13 | 1.24 |
| Arformoterol 25 Mcg 2x/Day | 12.37 | 31.07 | 37.00 |
| Formoterol 12 Mcg 2x/Day | 15.28 | 16.05 | 24.42 |
The BODE index (0=relative health and 10=severe chronic obstructive pulmonary disease) is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the 6-minute walk test. Scores were derived using pre-dose assessments from each visit. (NCT00250679)
Timeframe: Baseline (visit 2), weeks 13, 26
| Intervention | units on a scale (Mean) | ||
|---|---|---|---|
| Visit 2 (baseline- week 0) n=146,148,147 | Visit 4 (week 13) n=110,108,109 | Visit 5 (week 26) n=103,100,101 | |
| Arformoterol 15 Mcg 2x/Day | 4.98 | 3.97 | 3.94 |
| Arformoterol 25 Mcg 2x/Day | 5.14 | 4.28 | 4.11 |
| Formoterol 12 Mcg 2x/Day | 4.82 | 4.22 | 3.92 |
The 24 hour trough is the FEV1 value obtained 24 hours post first dose. This value is compared to the baseline FEV1 value. (NCT00250679)
Timeframe: weeks 0,3,13,26
| Intervention | Liters (Mean) | |||
|---|---|---|---|---|
| Visit 2 (week 0) n=141,143,141 | Visit 3 (week 3) n=130,130,127 | Visit 4 (week 13) n=111,108,110 | Visit 5 (week 26) n=105,97,101 | |
| Arformoterol 15 Mcg 2x/Day | 0.172 | 0.124 | 0.116 | 0.098 |
| Arformoterol 25 Mcg 2x/Day | 0.155 | 0.131 | 0.101 | 0.137 |
| Formoterol 12 Mcg 2x/Day | 0.162 | 0.096 | 0.094 | 0.087 |
Mean Change in Inspiratory Capacity values from baseline (baseline assessment obtained at Visit 2, pre-dose). Spirometry measurements collected within 6 hours following in-clinic rescue/supplemental medications use were excluded from analysis. (NCT00250679)
Timeframe: weeks 0,3,13,26
| Intervention | Liter (Mean) | ||||||
|---|---|---|---|---|---|---|---|
| Visit 2 (wk 0): 2 hours Post-dose n=79,85,80 | Visit 3 (wk 3): Pre-Dose n=74,77,69 | Visit 3 (wk 3): 2 hours Post-dose n=75,75,69 | Visit 4 (wk 13): Pre-Dose n=62,63,58 | Visit 4 (wk 13): 2 hours Post-Dose n=60,63,58 | Visit 5 (wk 26): Pre-Dose n=58,58,53 | Visit 5 (wk 26): 2 hours Post-Dose n=58,58,53 | |
| Arformoterol 15 Mcg 2x/Day | 0.297 | 0.032 | 0.241 | 0.005 | 0.233 | 0.057 | 0.202 |
| Arformoterol 25 Mcg 2x/Day | 0.330 | 0.124 | 0.331 | 0.124 | 0.284 | 0.154 | 0.368 |
| Formoterol 12 Mcg 2x/Day | 0.240 | 0.058 | 0.206 | 0.114 | 0.290 | 0.039 | 0.234 |
The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. Ratings were assessed relative to the subject's initial entry into the study. (NCT00250679)
Timeframe: weeks 13, 26
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Visit 4 (week 13) n=111,112,110 | Visit 5 (week 26) n=106,100,100 | |
| Arformoterol 15 Mcg 2x/Day | -0.88 | -0.74 |
| Arformoterol 25 Mcg 2x/Day | -0.75 | -0.76 |
| Formoterol 12 Mcg 2x/Day | -0.66 | -0.74 |
Supplemental medication usage is recorded throughout the study. MDI stands for metered dose inhaler. (NCT00250679)
Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)
| Intervention | Days Used / Week (Mean) | |
|---|---|---|
| Screening Period (day -14 to day 0 pre-dose) | Visits 2-5 (week 0 - 26) | |
| Arformoterol 15 Mcg 2x/Day | 3.73 | 2.36 |
| Arformoterol 25 Mcg 2x/Day | 3.84 | 2.52 |
| Formoterol 12 Mcg 2x/Day | 4.10 | 2.66 |
Supplemental medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication. (NCT00250679)
Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)
| Intervention | Actuations / Day (Mean) | |
|---|---|---|
| Screening period (day -14 to day 0 pre-dose) | Visits 2-5 (week 0 - 26) | |
| Arformoterol 15 Mcg 2x/Day | 2.43 | 1.59 |
| Arformoterol 25 Mcg 2x/Day | 2.67 | 1.58 |
| Formoterol 12 Mcg 2x/Day | 2.70 | 1.61 |
Scores are expressed as a mean change from baseline of overall impairment (total score). The questionnaire has a scale of 100 which represents worst possible health status to 0 which indicates best possible health status. (NCT00250679)
Timeframe: weeks 13, 26
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Visit 4 (week 13) n=105,102,105 | Visit 5 (week 26) n=97,94,97 | |
| Arformoterol 15 Mcg 2x/Day | -3.44 | -3.73 |
| Arformoterol 25 Mcg 2x/Day | -1.92 | -3.68 |
| Formoterol 12 Mcg 2x/Day | -4.16 | -6.76 |
Forced Expiratory Volume in one second (NCT00250679)
Timeframe: Baseline (Visit 2), weeks 3, 13, 26
| Intervention | Liters (Mean) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Visit 2 (wk 0, baseline) pre dose; n=147,149,147 | Visit 2 (wk 0) 24 hr; n=141,143,141 | Visit 3 (wk 3) pre dose; n=129,129,132 | Visit 3 (wk 3) 24 hr; n=130,130,127 | Visit 4 (wk 13) pre dose; n=113,111,111 | Visit 4 (wk 13) 24 hr; n=111,108,110 | Visit 5 (wk 26) pre dose; n=107,102,101 | Visit 5 (wk 26) 24 hr; n=105,97,101 | Visit 2 (wk 0) 6 hr; n=142,145,138 | Visit 3 (wk 3) 6 hr; n=130,125,127 | Visit 4 (wk 13) 6 hr; n=109,109,104 | Visti 5 (wk 26) 6 hr; n=101,95,101 | |
| Arformoterol 15 Mcg 2x/Day | 1.222 | 1.400 | 1.323 | 1.346 | 1.310 | 1.331 | 1.291 | 1.314 | 1.410 | 1.386 | 1.385 | 1.355 |
| Arformoterol 25 Mcg 2x/Day | 1.204 | 1.360 | 1.327 | 1.355 | 1.308 | 1.294 | 1.325 | 1.360 | 1.428 | 1.386 | 1.361 | 1.384 |
| Formoterol 12 Mcg 2x/Day | 1.210 | 1.378 | 1.311 | 1.310 | 1.281 | 1.316 | 1.283 | 1.296 | 1.383 | 1.338 | 1.339 | 1.310 |
Inspiratory capacity is the maximum volume that can be inhaled. (NCT00250679)
Timeframe: Baseline (Visit 2), Weeks 3, 13, 26
| Intervention | Liters (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Visit 2 (wk 0, baseline) pre-dose; n=80,86,82 | Visit 3 (wk 3) pre-dose; n=81,83,74 | Visit 4 (wk 13) pre-dose; n=100,94,99 | Visit 5 (wk 26) pre-dose; n=106,101,101 | Visit 2 (wk 0, baseline) post dose; n=80,85,81 | VIsit 3 (wk 3) post dose; n=82,81,74 | Visit 4 (wk 13) post dose; n=98,94,99 | Visit 5 (wk 26) post dose; n=105,100,101 | |
| Arformoterol 15 Mcg 2x/Day | 1.864 | 1.889 | 1.890 | 1.901 | 2.161 | 2.111 | 2.081 | 2.084 |
| Arformoterol 25 Mcg 2x/Day | 1.764 | 1.909 | 1.962 | 2.070 | 2.109 | 2.108 | 2.176 | 2.273 |
| Formoterol 12 Mcg 2x/Day | 1.739 | 1.826 | 1.874 | 1.817 | 1.976 | 1.973 | 2.089 | 1.978 |
The investigator global evaluation is reported by the study investigator. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. (NCT00250679)
Timeframe: Baseline (Visit 2), Weeks 13, 26
| Intervention | units on a scale (Mean) | ||
|---|---|---|---|
| Visit 2 (Baseline, Week 0) n=145,148,144 | Visit 4 (week 13) n=113,112,112 | Visit 5 (week 26) n=107,100,102 | |
| Arformoterol 15 Mcg 2x/Day | 3.88 | 3.04 | 3.16 |
| Arformoterol 25 Mcg 2x/Day | 3.84 | 3.04 | 3.01 |
| Formoterol 12 Mcg 2x/Day | 3.73 | 3.12 | 3.08 |
A questionnaire to assess respiratory health. Scores are expressed as a percentage of overall impairment (total score), where 100 represents the worst possible health status and 0 indicates best possible health status. (NCT00250679)
Timeframe: Baseline (Visit 2), weeks 13, 26
| Intervention | units on a scale (Mean) | ||
|---|---|---|---|
| Visit 2 (Baseline; week 0) n=136,141,144 | Visit 4 (week 13) n=114, 105, 108 | Visit 5 (week 26) n=105, 97, 99 | |
| Arformoterol 15 Mcg 2x/Day | 49.36 | 43.64 | 42.69 |
| Arformoterol 25 Mcg 2x/Day | 52.40 | 49.95 | 48.09 |
| Formoterol 12 Mcg 2x/Day | 48.86 | 43.48 | 41.72 |
The subject global evaluation is reported by study subjects/participants. It is a COPD symptoms rating ranging from 1 to 7, with 1 = much better and 7 = much worse. (NCT00250679)
Timeframe: Baseline (Visit 2), weeks 13, 26
| Intervention | units on a scale (Mean) | ||
|---|---|---|---|
| Visit 2 (baseline; week 0) n=145, 148, 146 | Visit 4 (week 13) n=114, 113, 115 | Visit 5 (week 26) n=108, 103, 103 | |
| Arformoterol 15 Mcg 2x/Day | 3.97 | 2.88 | 2.96 |
| Arformoterol 25 Mcg 2x/Day | 3.86 | 2.94 | 2.94 |
| Formoterol 12 Mcg 2x/Day | 3.73 | 2.83 | 2.86 |
This test measures the participants' level of fitness. It is a measure of the distance the participant can walk in 6 minutes. (NCT00250679)
Timeframe: Baseline (Visit 2), week 13, week 26
| Intervention | meters (Mean) | |||||
|---|---|---|---|---|---|---|
| Visit 2 (week 0) Pre-Dose n=147, 148, 147 | Visit 2 (week 0) Post-Dose n=146, 149, 146 | Visit 4 (week 13) Pre-Dose n=115, 111, 111 | Visit 4 (week 13) Post-Dose n=116, 111, 112 | Visit 5 (week 26) Pre-Dose n=105, 100, 103 | Visit 5 (week 26) Post-Dose n=106, 98, 103 | |
| Arformoterol 15 Mcg 2x/Day | 315.94 | 332.80 | 332.25 | 337.28 | 338.21 | 344.98 |
| Arformoterol 25 Mcg 2x/Day | 328.36 | 339.81 | 333.63 | 337.68 | 337.25 | 348.11 |
| Formoterol 12 Mcg 2x/Day | 334.84 | 352.19 | 344.95 | 352.51 | 355.83 | 361.72 |
Scores range from 0 to 4, with a score of 4 indicating that a subject is too breathless to leave the house or becomes breathless when dressing or undressing. The highest numbered question to which the subject answered 'Yes' is the Dyspnea Scale Score. (NCT00250679)
Timeframe: Baseline (visit 2), weeks 13, 26
| Intervention | units on a scale (Mean) | |||
|---|---|---|---|---|
| Baseline (visit 2, week 0) n=147,149,145 | Visit 3 (week 3) n=132,131,128 | Visit 4 (week 13) n=117,113,115 | Visit 5 (week 26) n=107,103,103 | |
| Arformoterol 15 Mcg 2x/Day | 2.76 | 2.47 | 2.10 | 2.09 |
| Arformoterol 25 Mcg 2x/Day | 2.91 | 2.50 | 2.43 | 2.26 |
| Formoterol 12 Mcg 2x/Day | 2.73 | 2.33 | 2.35 | 2.16 |
Scores are expressed as the number of participants with >= 4 unit improvement in overall impairment (total score), where 100 represents worst possible health status and 0 indicates best possible health status. (NCT00250679)
Timeframe: Visit 4 (week 13) , Visit 5 (week 26)
| Intervention | Participants (Number) | |
|---|---|---|
| Visit 4 (week 13) n=105,102,105 | Visit 5 (week 26) n=97,94,97 | |
| Arformoterol 15 Mcg 2x/Day | 47 | 43 |
| Arformoterol 25 Mcg 2x/Day | 39 | 42 |
| Formoterol 12 Mcg 2x/Day | 49 | 55 |
The number of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score compares current health against baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement. (NCT00250679)
Timeframe: weeks 13, 26
| Intervention | Participants (Number) | |
|---|---|---|
| >= 1Unit Improvement, visit 4 (wk13) n=115,113,114 | >= 1 Unit Improvement,visit 5(wk 26) n=108,102,103 | |
| Arformoterol 15 Mcg 2x/Day | 59 | 49 |
| Arformoterol 25 Mcg 2x/Day | 61 | 54 |
| Formoterol 12 Mcg 2x/Day | 59 | 56 |
Patients with glucose values that met low (<=40 mg/dL) or high (>=175 mg/dL) criteria were considered potentially clinically significant. (NCT00250679)
Timeframe: visit 6 (week 27)
| Intervention | Participants (Number) | |
|---|---|---|
| <=40 mg/dL | >=175 mg/dL | |
| Arformoterol 15 Mcg 2x/Day | 0 | 55 |
| Arformoterol 25 Mcg 2x/Day | 1 | 54 |
| Formoterol 12 Mcg 2x/Day | 1 | 20 |
Number of subjects with a heart rate that was lower/higher than a set limit and increased/decreased from set baseline limit in beats per minute (bpm) (NCT00250679)
Timeframe: visit 6 (week 27)
| Intervention | Participants (Number) | |
|---|---|---|
| < 50 bpm & >= 15 bpm | < 120 bpm & >= 25 bpm | |
| Arformoterol 15 Mcg 2x/Day | 5 | 1 |
| Arformoterol 25 Mcg 2x/Day | 2 | 1 |
| Formoterol 12 Mcg 2x/Day | 6 | 2 |
Patients with potassium values that met low (<=3 mEq/L) or high (>=6 mEq/L) criteria were considered potentially clinically significant. (NCT00250679)
Timeframe: visit 6 (week 27)
| Intervention | Participants (Number) | |
|---|---|---|
| <= 3mEq/L | >= 6mEq/L | |
| Arformoterol 15 Mcg 2x/Day | 4 | 1 |
| Arformoterol 25 Mcg 2x/Day | 3 | 1 |
| Formoterol 12 Mcg 2x/Day | 2 | 4 |
Percent of participants with a >=4 unit improvement in the overall impairment (total score) of the St. George's Respiratory Questionaire. This questionaire uses a 100 - 0 scale, where 100 represents the worst possible health status and 0 indicates the best possible health status. (NCT00250679)
Timeframe: visit 4 (week 13), visit 5 (week 26)
| Intervention | percent of participants (Number) | |
|---|---|---|
| Visit 4 (week 13), n=105,102,105 | Visit 5 (week 26), n=97,94,97 | |
| Arformoterol 15 Mcg 2x/Day | 46.1 | 45.7 |
| Arformoterol 25 Mcg 2x/Day | 37.1 | 43.3 |
| Formoterol 12 Mcg 2x/Day | 46.7 | 56.7 |
"Percent of participants with the adverse event specified.~SOC = system organ class." (NCT00250679)
Timeframe: Six months
| Intervention | percent of participants (Number) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any AE | Any Severe AE | Any Potentially Related AE | Any Beta-Mediated AE | Any AE w SOC of Cardiac Disorders | Any Serious AE | Any AE Leading to Discontinuation | Any COPD Exacerbation (Protocol Definition) | Any COPD Exacerbation (Expanded Definition) | Any Ischaemic AE | Any Arrhythmnic AE | Any AE w SOC Respiratory, Thoracic, & Mediastinal | |
| Arformoterol 15 Mcg 2x/Day | 67.8 | 13.4 | 32.9 | 10.7 | 6.0 | 13.4 | 10.1 | 32.2 | 35.6 | 0.7 | 3.4 | 34.2 |
| Arformoterol 25 Mcg 2x/Day | 76.2 | 11.6 | 34.7 | 15.6 | 6.1 | 6.8 | 12.2 | 30.6 | 38.1 | 5.4 | 1.4 | 34.0 |
| Formoterol 12 Mcg 2x/Day | 66.7 | 10.9 | 34.7 | 17.0 | 6.1 | 9.5 | 8.2 | 22.4 | 27.9 | 1.4 | 3.4 | 27.2 |
The percentage of participants with a transitional focal score (range -9 to 9) of >=1 improvement. Transitional focal score is the sum of the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores. A score of -9 is maximum worsening and 9 is maximum improvement. (NCT00250679)
Timeframe: visits 4 (week 13), visit 5 (week 26)
| Intervention | percent of participants (Number) | |
|---|---|---|
| >=1 Unit Improvement,visit 4 (wk 13) n=115,113,114 | >=1 Unit Improvement,visit 5 (wk 26) n=108,102,103 | |
| Arformoterol 15 Mcg 2x/Day | 52.2 | 48.0 |
| Arformoterol 25 Mcg 2x/Day | 53.5 | 52.4 |
| Formoterol 12 Mcg 2x/Day | 51.3 | 51.9 |
Rescue medication usage during the study. MDI stands for metered dose inhaler. (NCT00250679)
Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)
| Intervention | Days Used / Week (Mean) | |
|---|---|---|
| Screening Period (day -14 to day 0 pre-dose) | Visits 2-5 (week 0 - 26) | |
| Arformoterol 15 Mcg 2x/Day | 4.20 | 2.44 |
| Arformoterol 25 Mcg 2x/Day | 4.23 | 2.75 |
| Formoterol 12 Mcg 2x/Day | 4.18 | 2.85 |
The global evaluation is a COPD symptoms rating ranging from 1 to 7, with 1=much better and 7=much worse. Ratings were assessed relative to the subject's initial entry into the study. (NCT00250679)
Timeframe: weeks 13, 26
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Visit 4 (week 13) n=112,112,114 | Visit 5 (week 26) n=106,102,102 | |
| Arformoterol 15 Mcg 2x/Day | -1.11 | -1.06 |
| Arformoterol 25 Mcg 2x/Day | -0.89 | -0.83 |
| Formoterol 12 Mcg 2x/Day | -0.96 | -0.97 |
Area under the change from baseline curve from 0 to 6 hours. Time-normalized AUC (0-6 hrs) was derived using the linear trapezoidal method. (NCT00250679)
Timeframe: weeks 0,3,13,26
| Intervention | Liter (Mean) | |||
|---|---|---|---|---|
| Visit 2 (week 0) n=147,149,147 | Visit 3 (week 3) n=129,129,131 | Visit 4 (week 13) n=113,110,110 | Visit 5 (week 26) n=107,100,101 | |
| Arformoterol 15 Mcg 2x/Day | 0.216 | 0.208 | 0.214 | 0.197 |
| Arformoterol 25 Mcg 2x/Day | 0.253 | 0.224 | 0.218 | 0.241 |
| Formoterol 12 Mcg 2x/Day | 0.191 | 0.175 | 0.155 | 0.161 |
The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A Transitional Dyspnea Index score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests. (NCT00250679)
Timeframe: weeks 13, 26
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Visit 4 (week 13) n=115,113,114 | Visit 5 (week 26) n=108,102,103 | |
| Arformoterol 15 Mcg 2x/Day | 1.47 | 1.43 |
| Arformoterol 25 Mcg 2x/Day | 1.56 | 1.49 |
| Formoterol 12 Mcg 2x/Day | 1.50 | 1.44 |
Rescue medication usage during the study. MDI stands for metered dose inhaler. An actuation is one depression of the device that releases medication. (NCT00250679)
Timeframe: Screening (day-14 to 0) and Treatment (week 0 - 26)
| Intervention | Actuations/Day (Mean) | |
|---|---|---|
| Screening Period (day -14 to day 0 pre-dose) | Visits 2-5 (week 0 - 26) | |
| Arformoterol 15 Mcg 2x/Day | 2.68 | 1.56 |
| Arformoterol 25 Mcg 2x/Day | 2.97 | 1.65 |
| Formoterol 12 Mcg 2x/Day | 2.91 | 1.71 |
The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. The comparison was for MF/F versus MF. Standard deviation was pooled. (NCT00381485)
Timeframe: Baseline to Week 12
| Intervention | Liter x hour (Least Squares Mean) |
|---|---|
| MF/F MDI 400/10 mcg BID | 4.19 |
| MF/F MDI 200/10 mcg BID | 3.59 |
| MF MDI 400 mcg BID | 2.04 |
AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). The AQLQ(S) Total score was the mean of the individual 32 questions. The comparison was for MF/F versus placebo. Standard deviation was pooled. (NCT00381485)
Timeframe: Baseline to Week 12
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| MF/F MDI 400/10 mcg BID | 0.51 |
| MF/F MDI 200/10 mcg BID | 0.61 |
| MF MDI 400 mcg BID | 0.50 |
ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). The ACQ Total score was the mean of the individual seven questions. The comparison was for MF/F versus placebo. Standard deviation was pooled. (NCT00381485)
Timeframe: Baseline to Week 12
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| MF/F MDI 400/10 mcg BID | -0.58 |
| MF/F MDI 200/10 mcg BID | -0.59 |
| MF MDI 400 mcg BID | -0.42 |
Baseline was the proportion of nights of the last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0 = no awakenings to 1 = awakenings every night. The comparison was for MF/F versus placebo. Standard deviation was pooled. (NCT00381485)
Timeframe: 12-week Treatment Period
| Intervention | Proportion of nights (Least Squares Mean) |
|---|---|
| MF/F MDI 400/10 mcg BID | -0.10 |
| MF/F MDI 200/10 mcg BID | -0.10 |
| MF MDI 400 mcg BID | -0.05 |
AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). Standard deviations are pooled. (NCT00383240)
Timeframe: Baseline to Week 26
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Baseline (n=183/189/187/189, respectively) | Change from Baseline to Endpoint (26 weeks) | |
| F MDI 10 mcg BID | 5.51 | 0.05 |
| MF MDI 200 mcg BID | 5.40 | 0.37 |
| MF/F MDI 200/10 mcg BID | 5.38 | 0.49 |
| Placebo BID | 5.56 | -0.01 |
(NCT00383240)
Timeframe: Baseline to Endpoint (12 weeks)
| Intervention | liters x hours (Least Squares Mean) | |
|---|---|---|
| Baseline (n=188/189/198/192, respectively) | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 2.73 | 1.60 |
| MF MDI 200 mcg BID | 1.29 | 1.31 |
| MF/F MDI 200/10 mcg BID | 3.20 | 3.19 |
| Placebo BID | 1.42 | 0.51 |
Baseline is the proportion of nights of last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0=no awakenings to 1=awakenings every night. Standard deviation is pooled. (NCT00383240)
Timeframe: Baseline to Endpoint
| Intervention | Ratio (Least Squares Mean) | |
|---|---|---|
| Baseline (n=186/191/199/194, respectively) | Change from Baseline to Endpoint | |
| F MDI 10 mcg BID | 0.16 | 0.01 |
| MF MDI 200 mcg BID | 0.16 | -0.05 |
| MF/F MDI 200/10 mcg BID | 0.18 | -0.08 |
| Placebo BID | 0.15 | 0.00 |
This endpoint was to measure the time it took for 50% of subjects in a treatment arm to experience a severe asthma exacerbation (also see the posted Other Pre-specified Outcome: Number of Participants With at Least One Severe Asthma Exacerbation) (NCT00383240)
Timeframe: 26-week Treatment Period
| Intervention | days (Median) |
|---|---|
| MF/F MDI 200/10 mcg BID | NA |
| MF MDI 200 mcg BID | NA |
| F MDI 10 mcg BID | 92 |
| Placebo BID | 131 |
"A severe asthma exacerbation was defined as a clinically judged deterioration of asthma or a meaningful reduction in lung function based on any of the following criteria during the Treatment Period:~A decrease in FEV1 below the Treatment Period stability limit at any visit,~A decrease in AM or PM peak flow below the Treatment Period stability limits on any 2 consecutive days,~An occurrence of any clinical deterioration of asthma (ie, asthma attack) that resulted in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication." (NCT00383240)
Timeframe: Baseline to Week 26
| Intervention | participants (Number) |
|---|---|
| MF/F MDI 200/10 mcg BID | 58 |
| MF MDI 200 mcg BID | 65 |
| F MDI 10 mcg BID | 109 |
| Placebo BID | 109 |
ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). (NCT00383240)
Timeframe: Baseline to week 26
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Baseline (n=179/186/184/187, respectively) | Change from Baseline to Endpoint (week 26) | |
| F MDI 10 mcg BID | 1.43 | 0.11 |
| MF MDI 200 mcg BID | 1.46 | -0.23 |
| MF/F MDI 200/10 mcg BID | 1.47 | -0.40 |
| Placebo BID | 1.41 | 0.14 |
FEV1 AUC was standardized to liters. Endpoint was the last post-baseline non-missing result through Week 13 carried forward. (NCT00383435)
Timeframe: Baseline to Endpoint (13 weeks)
| Intervention | Liters (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 1.252 | 0.077 |
| MF MDI 400 mcg BID | 1.255 | 0.057 |
| MF/F MDI 200/10 mcg BID | 1.227 | 0.126 |
| MF/F MDI 400/10 mcg BID | 1.186 | 0.166 |
| Placebo | 1.227 | 0.003 |
"Endpoint was the last post-baseline non-missing result through Week 13 carried~forward." (NCT00383435)
Timeframe: Baseline to Endpoint (13 weeks)
| Intervention | Liters (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 1.252 | 0 |
| MF MDI 400 mcg BID | 1.258 | 0.027 |
| MF/F MDI 200/10 mcg BID | 1.223 | 0.058 |
| MF/F MDI 400/10 mcg BID | 1.191 | 0.111 |
| Placebo | 1.230 | -0.017 |
Mild = 12 or more inhalations/day of inhaled rescue medication or 2 or more nebulized treatments/day of inhaled rescue medication. Moderate = treatment with antibiotics or oral steroids. Severe = emergency room treatment or hospitalizations of survival curves. If an event was composed of multiple criteria, the most severe criteria was assigned to the event. (NCT00383435)
Timeframe: Endpoint (26 weeks)
| Intervention | Participants (Number) | ||
|---|---|---|---|
| Mild | Moderate | Severe | |
| F MDI 10 mcg BID | 45 | 30 | 4 |
| MF MDI 400 mcg BID | 41 | 30 | 1 |
| MF/F MDI 200/10 mcg BID | 48 | 23 | 0 |
| MF/F MDI 400/10 mcg BID | 41 | 14 | 1 |
| Placebo | 41 | 25 | 3 |
SGRQ consisted of 76 items aggregated into 3 component scores: symptoms (frequency/severity), activity (cause or limited by breathlessness), impact (social functioning, psychological disturbances from airway disease), & total score. Best health scores have a low numeric value. All component scores & total score range from 0-100, with a higher score indicating greater disease burden. A 4-point increase over placebo (and Baseline) was considered the minimum clinically important difference. Endpoint is the last post-baseline non-missing result through the 26 week evaluation carried forward. (NCT00383435)
Timeframe: Baseline to Endpoint (26 weeks)
| Intervention | Score on a scale (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 44.87 | -6.18 |
| MF MDI 400 mcg BID | 47.00 | -6.99 |
| MF/F MDI 200/10 mcg BID | 45.89 | -5.69 |
| MF/F MDI 400/10 mcg BID | 45.05 | -7.43 |
| Placebo | 44.60 | -2.87 |
Prior to the use of study drug rescue medication (in the morning upon awakening) the participant evaluated the COPD symptoms of wheezing, cough, and difficulty breathing. A symptom-free night was defined as a combined score of 0 (no symptoms) across all three COPD symptoms evaluated the following morning. Proportion for Baseline included data from the last week before the first dose. Proportion for Endpoint included data across the entire 26-week treatment period. (NCT00383435)
Timeframe: Baseline to Endpoint (26 weeks)
| Intervention | Proportion of symptom-free nights (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 0.35 | 0.14 |
| MF MDI 400 mcg BID | 0.33 | 0.11 |
| MF/F MDI 200/10 mcg BID | 0.29 | 0.07 |
| MF/F MDI 400/10 mcg BID | 0.31 | 0.15 |
| Placebo | 0.31 | 0.06 |
"Partly stable COPD was a composite measure that included the following COPD~outcomes: (1) No oral steroid rescue medication; (2) No AM or PM COPD weekly average symptom score greater than 2 during at least 7 of 8 weeks; (3) No moderate or severe exacerbations; (4) No unscheduled visits due to COPD worsenings; (5) No study discontinuation due to treatment failure or~treatment-related adverse event as determined by the investigator." (NCT00383435)
Timeframe: Endpoint (26 weeks)
| Intervention | Participants (Number) |
|---|---|
| MF/F MDI 400/10 mcg BID | 82 |
| MF/F MDI 200/10 mcg BID | 95 |
| MF MDI 400 mcg BID | 83 |
| F MDI 10 mcg BID | 90 |
| Placebo | 85 |
Baseline is the proportion of nights of the last week (Days -7 to 1) prior to first dose with nocturnal awakenings. Scale is measured as 0 to 1 with 0=no awakenings to 1=awakenings every night. The comparison was for MF/F vs placebo. Standard deviation was pooled. (NCT00383552)
Timeframe: Baseline to Endpoint
| Intervention | Proportion of Nights (Least Squares Mean) | |
|---|---|---|
| Baseline | Change from Baseline | |
| F MDI 10 mcg BID | 0.15 | -0.03 |
| MF MDI 100 mcg BID | 0.12 | -0.03 |
| MF/F MDI 100/10 mcg BID | 0.13 | -0.06 |
| Placebo BID | 0.13 | 0.02 |
Trough FEV1 is a measure of the end-of-dosing interval. The comparison was for MF/F vs F. Standard deviation was pooled. (NCT00383552)
Timeframe: Baseline to Week 12
| Intervention | liters (Least Squares Mean) | |
|---|---|---|
| Baseline | Change from Baseline | |
| F MDI 10 mcg BID | 2.47 | 0.11 |
| MF MDI 100 mcg BID | 2.41 | 0.16 |
| MF/F MDI 100/10 mcg BID | 2.50 | 0.18 |
| Placebo BID | 2.46 | 0.04 |
Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days and or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication. (NCT00383552)
Timeframe: Week 26
| Intervention | participants (Number) |
|---|---|
| MF/F MDI 100/10 mcg BID | 30 |
| MF MDI 100 mcg BID | 53 |
| F MDI 10 mcg BID | 84 |
| Placebo BID | 86 |
Severe asthma exacerbation refers to an occurrence of a decrease below 80% of Baseline in FEV1, a decrease below 70% of Baseline in PEF on 2 consecutive days or a clinical deterioration of asthma resulting in emergency treatment, hospitalization or treatment with asthma medication. (NCT00383552)
Timeframe: Across the 26 week treatment period
| Intervention | Days (Median) |
|---|---|
| MF/F MDI 100/10 Mcg BID | 45.5 |
| MF MDI 100 Mcg BID | 54 |
| F MDI 10 Mcg BID | 51.5 |
| Placebo BID | 27.5 |
The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. BMI is a number calculated from a person's weight and height. The higher the number, the higher the amount of fat. The comparison was for MF/F vs placebo. Standard deviation was pooled. (NCT00383552)
Timeframe: Baseline to Week 12
| Intervention | liters * hours (Least Squares Mean) | ||
|---|---|---|---|
| Less than 25 | 25 to less than 30 | 30 or more | |
| F MDI 10 mcg BID | 4.34 | 4.26 | 3.13 |
| MF MDI 100 mcg BID | 3.19 | 3.23 | 1.69 |
| MF/F MDI 100/10 mcg BID | 5.24 | 3.36 | 3.35 |
| Placebo BID | 2.22 | 1.22 | -0.73 |
The average of the two predose FEV1 measurements (30 minutes prior to dosing and 0 hour, immediately prior to dosing) at the Baseline Visit were subtracted from each of the serial measurements over the 12-hour period. The AUC was calculated based on these changes from Baseline evaluations. The comparison was for MF/F vs MF. Standard deviation was pooled. (NCT00383552)
Timeframe: Baseline to Week 12
| Intervention | liters * hours (Least Squares Mean) | |
|---|---|---|
| Baseline | Change from Baseline | |
| F MDI 10 mcg BID | 4.09 | 3.83 |
| MF MDI 100 mcg BID | 1.85 | 2.53 |
| MF/F MDI 100/10 mcg BID | 3.94 | 4.00 |
| Placebo BID | 1.64 | 1.11 |
ACQ consists of seven questions each scaled from 0 (best case) to 6 (worst case). The comparison was for MF/F vs placebo. Standard deviation was pooled. (NCT00383552)
Timeframe: Baseline to Week 26
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Baseline | Change from Baseline | |
| F MDI 10 mcg BID | 1.38 | -0.12 |
| MF MDI 100 mcg BID | 1.29 | -0.32 |
| MF/F MDI 100/10 mcg BID | 1.34 | -0.40 |
| Placebo BID | 1.23 | -0.11 |
AQLQ(S) consists of 32 questions each scaled from 1 (worst case) to 7 (best case). The comparison was for MF/F vs placebo. Standard deviation was pooled. (NCT00383552)
Timeframe: Baseline to Week 26
| Intervention | units on a scale (Least Squares Mean) | |
|---|---|---|
| Baseline | Change from Baseline | |
| F MDI 10 mcg BID | 5.60 | 0.15 |
| MF MDI 100 mcg BID | 5.65 | 0.39 |
| MF/F MDI 100/10 mcg BID | 5.60 | 0.44 |
| Placebo BID | 5.76 | 0.06 |
Prior to the use of study drug rescue medication (in the morning upon awakening) the participant evaluated the COPD symptoms of wheezing, cough, and difficulty breathing. A symptom-free night was defined as a combined score of 0 (no symptoms) across all three COPD symptoms evaluated the following morning. Proportion for Baseline included data from the last week before the first dose. Proportion for Endpoint included data across the entire 26-week treatment period. (NCT00383721)
Timeframe: Baseline to Endpoint (26 weeks)
| Intervention | Proportion of symptom-free nights (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 0.25 | 0.13 |
| MF MDI 400 mcg BID | 0.24 | 0.16 |
| MF/F MDI 200/10 mcg BID | 0.22 | 0.17 |
| MF/F MDI 400/10 mcg BID | 0.24 | 0.13 |
| Placebo | 0.24 | 0.12 |
"SGRQ consisted of 76 items aggregated into 3 component scores: symptoms~(frequency/severity), activity (cause or limited by breathlessness), impact (social functioning, psychological disturbances from airway disease), & total score. Best health scores have a low numeric value. All component scores & total score ranged from 0-100, with a higher score indicating greater disease burden. A 4-point increase over placebo (and Baseline) was considered the minimum clinically important difference. Endpoint was the last post-baseline non-missing result through the 26 week evaluation carried forward." (NCT00383721)
Timeframe: Baseline to Endpoint (26 weeks)
| Intervention | Score on a scale (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 46.27 | -4.93 |
| MF MDI 400 mcg BID | 48.27 | -5.87 |
| MF/F MDI 200/10 mcg BID | 47.29 | -7.99 |
| MF/F MDI 400/10 mcg BID | 48.22 | -6.04 |
| Placebo | 46.59 | -2.88 |
FEV1 AUC was standardized to liters. Endpoint was the last post-baseline non-missing result through Week 13 carried forward. (NCT00383721)
Timeframe: Baseline to Endpoint (13 weeks)
| Intervention | Liters (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 1.176 | 0.092 |
| MF MDI 400 mcg BID | 1.260 | 0.053 |
| MF/F MDI 200/10 mcg BID | 1.195 | 0.139 |
| MF/F MDI 400/10 mcg BID | 1.189 | 0.179 |
| Placebo | 1.205 | 0.018 |
Endpoint was the last post-baseline non-missing result through Week 13 carried forward. (NCT00383721)
Timeframe: Baseline to Endpoint (13 weeks)
| Intervention | Liters (Least Squares Mean) | |
|---|---|---|
| Baseline | Endpoint (Change from Baseline) | |
| F MDI 10 mcg BID | 1.175 | 0.049 |
| MF MDI 400 mcg BID | 1.255 | 0.028 |
| MF/F MDI 200/10 mcg BID | 1.194 | 0.063 |
| MF/F MDI 400/10 mcg BID | 1.188 | 0.098 |
| Placebo | 1.205 | -0.003 |
"Mild = 12 or more inhalations/day of inhaled rescue medication or 2 or more~nebulized treatments/day of inhaled rescue medication. Moderate = treatment with~antibiotics or oral steroids. Severe = emergency room treatment or hospitalizations of survival curves. If an event was composed of multiple criteria, the most severe criteria was assigned to the event." (NCT00383721)
Timeframe: Endpoint (26 weeks)
| Intervention | Participants (Number) | ||
|---|---|---|---|
| Mild | Moderate | Severe | |
| F MDI 10 mcg BID | 61 | 33 | 2 |
| MF MDI 400 mcg BID | 49 | 29 | 5 |
| MF/F MDI 200/10 mcg BID | 53 | 20 | 3 |
| MF/F MDI 400/10 mcg BID | 56 | 24 | 3 |
| Placebo | 64 | 38 | 4 |
"Partly stable COPD was a composite measure that included the following COPD~outcomes: (1) No oral steroid rescue medication; (2) No AM or PM COPD weekly~average symptom score greater than 2 during at least 7 of 8 weeks; (3) No moderate or severe exacerbations; (4) No unscheduled visits due to COPD worsenings; (5) No study discontinuation due to treatment failure or treatment-related adverse event as determined by the investigator." (NCT00383721)
Timeframe: Endpoint (26 weeks)
| Intervention | Participants (Number) |
|---|---|
| MF/F MDI 400/10 mcg BID | 91 |
| MF/F MDI 200/10 mcg BID | 101 |
| MF MDI 400 mcg BID | 92 |
| F MDI 10 mcg BID | 98 |
| Placebo | 87 |
The ACQ is a 7-point scale with scores ranging from 0 (very well controlled) to 6 (very badly controlled) (NCT00385593)
Timeframe: Daily 14 days prior to each of visit 2-4
| Intervention | Scores on a scale (Mean) |
|---|---|
| SMART | 0.99 |
| Conv. Best Practice | 1.08 |
Peak expiratory flow (PEF) (NCT00385593)
Timeframe: 6 months (end of the study)
| Intervention | L/min (Mean) |
|---|---|
| SMART | 405.9 |
| Conv. Best Practice | 400.6 |
Severe asthma exacerbation is defined as deterioration in asthma leading to at least one of Hospitalization/Emergency room (or equivalent) treatment due to asthma or Oral Glucocorticosteroids (GCS) treatment for at least 3 days. (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | Days (Mean) |
|---|---|
| SMART | 174.39 |
| Conv. Best Practice | 178.97 |
Severe asthma exacerbation is defined as deterioration in asthma leading to at least one of Hospitalization/Emergency room (or equivalent) treatment due to asthma or Oral (GCS) treatment for at least 3 days. (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | Exacerbations (Number) |
|---|---|
| SMART | 24 |
| Conv. Best Practice | 34 |
Mean use of as needed medication during the treatment period (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | Inhalations (Mean) |
|---|---|
| SMART | 1.03 |
| Conv. Best Practice | 1.02 |
Mean micrograms/day of inhaled steroids (beclomethasone dipropionate equivalents) (NCT00385593)
Timeframe: Baseline up to 6 months
| Intervention | micrograms (Mean) |
|---|---|
| SMART | 799 |
| Conv. Best Practice | 1184 |
Percentage of days of poor control was defined as the number of days in the patient diary with a score ≥ 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with ≥ 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. (NCT00393458)
Timeframe: Baseline to end of study (Week 52)
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Indacaterol 300 μg Plus Placebo to Formoterol | 33.6 |
| Indacaterol 600 μg Plus Placebo to Formoterol | 30.0 |
| Formoterol 12 μg Plus Placebo to Indacaterol | 33.5 |
| Placebo to Indacaterol Plus Placebo to Formoterol | 38.3 |
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. (NCT00393458)
Timeframe: Week 12 + 1 day, Day 85
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Indacaterol 300 μg Plus Placebo to Formoterol | 1.48 |
| Indacaterol 600 μg Plus Placebo to Formoterol | 1.48 |
| Formoterol 12 μg Plus Placebo to Indacaterol | 1.38 |
| Placebo to Indacaterol Plus Placebo to Formoterol | 1.31 |
Change in evening PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline evening PEF value. (NCT00419744)
Timeframe: 12 months
| Intervention | L/min (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | 17.62 |
| SYM 80/4.5 X 2 BID | 17.77 |
| FOR 4.5 X 2 BID | 14.08 |
Rate of exacerbations per subject-year (NCT00419744)
Timeframe: 12 months
| Intervention | Rate (Number) |
|---|---|
| SYM 160/4.5 X 2 BID | 0.639 |
| SYM 80/4.5 X 2 BID | 0.745 |
| FOR 4.5 X 2 BID | 1.029 |
Change from baseline in the use of beta-2 agonists, as calculated by averaging treatment period inhalations per day and subtracting the baseline number of inhalations per day. (NCT00419744)
Timeframe: 12 months
| Intervention | Number of inhalations (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | -1.21 |
| SYM 80/4.5 X 2 BID | -1.03 |
| FOR 4.5 X 2 BID | -0.28 |
Number of COPD-related exacerbations per patient-treatment year. COPD-related exacerbation was defined as worsening COPD that required a course of oral steriods for treatment and/or hospitalization. (NCT00419744)
Timeframe: 12 months
| Intervention | Exacerbations (Number) |
|---|---|
| SYM 160/4.5 X 2 BID | 0.75 |
| SYM 80/4.5 X 2 BID | 0.84 |
| FOR 4.5 X 2 BID | 1.14 |
Change from baseline in the SGRQ overall score, as calculated by averaging treatment period SGRQ scores and subtracting the baseline SGRQ scores. The SGRQ contains 3 domains: Symptoms (distress due to respiratory symptoms, 8 questions), Activity (disturbance of physical activity, 16 questions), and Impacts (overall impact on daily life and well-being, 26 questions). Lower scores are associated with less severe symptoms. (NCT00419744)
Timeframe: 12 months
| Intervention | Scores on a scale (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | -6.23 |
| SYM 80/4.5 X 2 BID | -5.00 |
| FOR 4.5 X 2 BID | -5.71 |
Change from baseline of Dyspnea symptoms evaluated using the breathlessness diary, a 5-point Likert-type scale, ranging from 0 to 4 with higher scores indicating a more severe manifestation of the Dyspnea symptom. Change from baseline was calculated by averaging treatment period Dyspnea scores and subtracting the baseline Dyspnea scores. (NCT00419744)
Timeframe: 12 months
| Intervention | Scores on a scale (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | -0.30 |
| SYM 80/4.5 X 2 BID | -0.29 |
| FOR 4.5 X 2 BID | -0.24 |
Change in pre-dose FEV1 from baseline to the average of the randomized treatment period, as calculated by averaging treatment period FEV1 values and subtracting the pre-dose value. (NCT00419744)
Timeframe: 12 months
| Intervention | Liters (L) (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | 0.07 |
| SYM 80/4.5 X 2 BID | 0.07 |
| FOR 4.5 X 2 BID | 0.04 |
Change in morning PEF from baseline to the average of the randomized treatment period, as calculated by averaging treatment period PEF values and subtracting the baseline morning PEF value. (NCT00419744)
Timeframe: 12 months
| Intervention | L/min (Mean) |
|---|---|
| SYM 160/4.5 X 2 BID | 19.82 |
| SYM 80/4.5 X 2 BID | 19.61 |
| FOR 4.5 X 2 BID | 15.81 |
Changes in pre-dose FEV1 from baseline to the average value over the treatment period, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline, 2, 6 and 12 weeks
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Symbicort | 0.16 |
| Budesonide | 0.11 |
Change from baseline in percentage of rescue-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Symbicort | 19.70 |
| Budesonide | 17.70 |
"Percentage of participants with Withdrawals Due to Pre-defined Asthma Events as recorded in CRF. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated." (NCT00419757)
Timeframe: 12 weeks
| Intervention | Percentage of Participants (Number) |
|---|---|
| Symbicort | 2.10 |
| Budesonide | 6.50 |
Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks with baseline as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Liters/minutes (Least Squares Mean) |
|---|---|
| Symbicort | 20.60 |
| Budesonide | 15.80 |
Change from baseline in rescue medication use over 12 weeks of treatment with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | puffs/day (Least Squares Mean) |
|---|---|
| Symbicort | -0.80 |
| Budesonide | -0.60 |
"The assessment was made using a 5-point Likert scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1 and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses." (NCT00419757)
Timeframe: Baseline and week 12
| Intervention | Percent of Participants (Number) |
|---|---|
| Symbicort | 88.70 |
| Budesonide | 86.30 |
"The assessment was made using a 5-point scale with 1=much better, 2=somewhat better, 3=comparable, 4=somewhat worse, and 5=much worse transformed to a binary variable with points 1and 2 combined as Yes and points 3, 4, 5 as No. Percent of Participants that gave positive responses." (NCT00419757)
Timeframe: Baseline and week 12
| Intervention | Perscentage of Participants (Number) |
|---|---|
| Symbicort | 92.00 |
| Budesonide | 84.60 |
Asthma Events, defined as any of: decrease in lung function (FEV1 or AM PEF), use of rescue medication over maximum allowed per day, night awakening requiring use of rescue medication, exacerbation of asthma requiring medical assistance, use of not allowed asthma medication (NCT00419757)
Timeframe: 12 weeks
| Intervention | Percentage of Participants (Number) |
|---|---|
| Symbicort | 25.20 |
| Budesonide | 31.70 |
Mean scores (6 or 5-points scale, where 1-means the most positive opinion and 5/6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. (NCT00419757)
Timeframe: Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 90.67 |
| Budesonide | 86.66 |
Mean scores (6-points scale, where 1-means the most positive opinion and 6-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. (NCT00419757)
Timeframe: Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 87.20 |
| Budesonide | 82.50 |
Mean scores (5-points scale, where 1-means the most positive opinion and 5-the most negative opinion) were calculated for items in domain. 6-point response options were scored on a 0±100 scale, where 100 represented the highest level of satisfaction and 0 the lowest level of satisfaction. (NCT00419757)
Timeframe: Week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 88.45 |
| Budesonide | 80.60 |
Change from baseline (average of daily records over the 14 days of run-in) to the average of daily records over the treatment period of 12 weeks, with baseline value as covariate. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Liters/minutes (Least Squares Mean) |
|---|---|
| Symbicort | 25.40 |
| Budesonide | 19.90 |
Change from baseline in percentage of symptom-free days over 12 weeks of treatment, with baseline value as covariate. Includes all subjects who were randomised, took at least one dose of study medication and contributed sufficient data for the endpoint to be calculated. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Symbicort | 24.40 |
| Budesonide | 21.00 |
"Change from baseline in average of daily scores for nighttime asthma over 12 weeks of treatment, with baseline value as covariate.~Daily scale:~0 = No symptoms~1 = Mild symptoms~2 = Moderate symptoms~3 = Severe symptoms" (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | -0.40 |
| Budesonide | -0.30 |
"Change from baseline in average of daily scores for daytime asthma over 12 weeks of treatment, with baseline value as covariate.~Daily scale:~0 = No symptoms~1 = Mild symptoms~2 = Moderate symptoms~3 = Severe symptoms" (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | -0.40 |
| Budesonide | -0.30 |
Change from baseline in percentage of nights with awakenings due to asthma over 12 weeks of treatment, with baseline value as covariate. (NCT00419757)
Timeframe: Baseline (run-in) and throughout 12 weeks
| Intervention | Percentage of nights (Least Squares Mean) |
|---|---|
| Symbicort | 5.40 |
| Budesonide | 5.50 |
Change in pre-dose FEV1 from baseline (end of run-in, visit 3) to the average of the randomized treatment period (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Symbicort | 0.08 |
| Budesonide | -0.01 |
Number of participants with at least 1 exacerbation (NCT00419952)
Timeframe: 52 Weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 29 |
| Budesonide | 51 |
Change in AM PEF from baseline (mean over the 2 weeks run-in) to the average of the randomized treatment period. (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | Liters/minute (Least Squares Mean) |
|---|---|
| Symbicort | 30.13 |
| Budesonide | 19.73 |
Total ectopic supraventricular (VE) beats - number of participants with shift normal (<50) to high (≥50) from baseline to visit 4. (NCT00419952)
Timeframe: Baseline and 2 weeks (visit 4)
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 4 |
| Budesonide | 3 |
Total ventricular runs - number of participants with shift normal (<1) to high (≥1) from baseline to week 2. (NCT00419952)
Timeframe: Baseline and 2 weeks (visit 4)
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 2 |
| Budesonide | 1 |
An exacerbation was defined as symptomatic worsening requiring oral/systemic glucocorticoid therapy and/or emergency room visit and/or urgent care center visit and/or hospitalization. (NCT00419952)
Timeframe: 52 Weeks
| Intervention | Exacerbations (Number) |
|---|---|
| Symbicort | 36 |
| Budesonide | 61 |
QT interval corrected using the Fridericia formula [QTc (Frid)] - Change from baseline to end of treatment (NCT00419952)
Timeframe: Baseline and 52 weeks
| Intervention | msec (Least Squares Mean) |
|---|---|
| Symbicort | -0.11 |
| Budesonide | -0.31 |
"Calculated as the number of rescue-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % rescue-free days in the baseline period and the active treatment period. A rescue-free day was one in which the patient answered no to having used rescue medication that day" (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | Percentage of Rescue Free Day (Least Squares Mean) |
|---|---|
| Symbicort | 15.88 |
| Budesonide | 10.62 |
Overall score - change from baseline to end of treatment. For 11 individual attributes, expectations were subtracted from the outcomes. This difference and the importance rating were combined in a weighted average which was then multiplied by the raw satisfaction measure. The final derived satisfaction measure was transformed to a 0 to 100 scale, with higher scores representing greater satisfaction. (NCT00419952)
Timeframe: Baseline and 52 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Symbicort | 47.99 |
| Budesonide | 45.64 |
"Number of participants with positive response to Item 5 in questionnaire During the past week, you were satisfied with how quickly you felt your study medication begin to work. The scale was scored on a 5-point Likert scale from strongly agree to strongly disagree. A positive response was defined as a response of strongly agree or somewhat agree" (NCT00419952)
Timeframe: 1 week
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 165 |
| Budesonide | 157 |
"Calculated as the number of symptom-free days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % symptom-free days in the baseline period and the active treatment period. A symptom-free day was one in which the patient answered no to having symptoms that day" (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | percentage of Symptom-free day (Least Squares Mean) |
|---|---|
| Symbicort | 9.46 |
| Budesonide | 7.58 |
Total ectopic ventricular (VE) beats - number of participants with shift from normal (<50) to high (≥50) from baseline to visit 4. (NCT00419952)
Timeframe: Baseline and 2 weeks (visit 4)
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 4 |
| Budesonide | 3 |
"Calculated as the number of asthma control days divided by the number of non missing days in the baseline period times 100%. The results are expressed as the change in % asthma control days in the baseline period and the active treatment period. An asthma control day was one in which the patient answered no to having symptoms and 0 to the use of rescue medication that day" (NCT00419952)
Timeframe: baseline and 52 weeks
| Intervention | percentage of Asthma-control day (Least Squares Mean) |
|---|---|
| Symbicort | 16.68 |
| Budesonide | 11.62 |
"Number of participants with positive response to Item 2 in questionnaire During the past week,you could feel your study medication begin to work right away. A positive response was defined as a response of strongly agree or somewhat agree" (NCT00419952)
Timeframe: 1 week
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 172 |
| Budesonide | 158 |
For each day of the evaluation period, symptoms were collected in the morning for the night's evaluation, and in the evening for the day's evaluation. Symptoms included coughing, wheezing, and difficulty breathing, each integer-scaled from 0=none to 3=severe. A symptom-free Day/Night is defined as a combined score of 0 across the morning and evening evaluations. The proportion of 0 scores across the Baseline period, and across the 12-week treatment period, is calculated to determine the overall proportion of symptom-free Days/Nights for each of these periods. (NCT00424008)
Timeframe: Baseline to Week 12
| Intervention | Proportion of symptom-free days/nights (Least Squares Mean) | ||
|---|---|---|---|
| Baseline (over the last week prior to first dose) | Actual proportion over the 12-wk treatment period | Change from Baseline to over the 12-wk tx period | |
| F/SC DPI 250/50 mcg BID | 0.18 | 0.43 | 0.25 |
| MF/F MDI 200/10 mcg BID | 0.19 | 0.42 | 0.24 |
The Asthma Control Questionnaire (ACQ) by Juniper et al. is a mean of 7 equally weighted composite scores; each scaled from 0=best case scenario to 6=worst case scenario on an integer scale. Composites include the following: How Often Woken by Asthma, How Bad Were Asthma Symptoms When You Woke, Activity Limitations, Shortness of Breath, Wheezing, Average Daily Short-Acting Beta 2-Agonist (SABA) Puffs, and physician-evaluated lung function. With the exception of physician-evaluated lung function collected at the visit, evaluations were over the last week recall period. (NCT00424008)
Timeframe: Baseline to Week 12
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| MF/F MDI 200/10 mcg BID | -0.65 |
| F/SC DPI 250/50 mcg BID | -0.65 |
PFTs, including FEV1, were done on Day 1. Evaluations included 30 min before and immediately before the first dose, the mean of which was Baseline, and at intervals from 5 min to 12 hrs postdose. Onset of action was defined as statistically significant improvement of MF/F over F/SC in Change from Baseline FEV1 at the 5-min postdose evaluation on Day 1. The same series of PFTs were done at Week 12. Change from Baseline to Week 12 evaluations were calculated using the same Day 1 predose scores for Baseline. The Week-12 evaluation consisted of AUC FEV1 scores across the 12-hour postdose interval. (NCT00424008)
Timeframe: Baseline to 5 minutes post-dose on Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| MF/F MDI 200/10 mcg BID | 0.20 |
| F/SC DPI 250/50 mcg BID | 0.09 |
(NCT00424008)
Timeframe: Baseline to Week 12
| Intervention | Liter x hour (Least Squares Mean) |
|---|---|
| MF/F MDI 200/10 mcg BID | 3.43 |
| F/SC DPI 250/50 mcg BID | 3.24 |
Baseline is FEV1 collected prior to first double-blind dose at week 0. Change is defined as Week 0 FEV1 percent predicted - Week 2 pre first dose FEV1 percent predicted. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Percent of predicted FEV1 (Mean) | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 0: Immediately post first dose; N=76, 78, 78 | Week 0: 30 minutes post first dose; N=75, 78, 76 | Week 0: 1 hour post first dose; N-75, 78, 77 | Week 0: 2 hours post first dose; N=76, 78, 77 | Week 0: 4 hours post first dose; N=75, 77, 77 | Week 0: 6 hours post first dose; N=72, 74, 77 | Week 0: 8 hours post first dose; N=70, 73, 77 | Week 0: 10 hours post first dose; N=69, 71, 76 | Week 0: 12 hours post first dose; N=69, 71, 75 | Week 2: Immediately post first dose; N=71, 75, 74 | Week 2: 30 minutes post first dose; N=70, 74, 74 | Week 2: 1 hour post first dose; N=71, 75, 73 | Week 2: 2 hours post first dose; N=71, 73, 74 | Week 2: 4 hours post first dose; N=69, 72, 74 | Week 2: 6 hours post first dose; N=69, 72, 73 | Week 2: 8 hours post first dose; N=69, 70, 74 | Week 2: 10 hours post first dose; N=69, 71, 71 | Week 2: 12 hours post first dose; N=63, 67, 71 | Week 2: Immediately post second dose; N=65, 67, 72 | Week 2: 12.5 hours post first dose; N=65, 66, 72 | Week 2: 13 hours post first dose; N=63, 68, 72 | Week 2: 14 hours post first dose; N=65, 71, 72 | Week 2: 16 hours post first dose; N=63, 70, 71 | Week 2: 23 hours post first dose; N=70, 74, 74 | Week 2: 24 hours post first dose; N=69, 73, 74 | |
| Arformoterol /Tiotropium | 4.7 | 6.1 | 6.3 | 8.1 | 7.5 | 7.3 | 6.6 | 6.5 | 6.7 | 8.0 | 9.3 | 10.2 | 11.0 | 9.2 | 8.8 | 7.4 | 6.8 | 6.3 | 7.8 | 9.0 | 9.1 | 9.8 | 8.0 | 4.8 | 5.2 |
| Arformoterol 15 Mcg Twice Daily | 4.3 | 5.5 | 6.1 | 6.6 | 5.3 | 4.4 | 3.5 | 3.3 | 1.6 | 5.1 | 6.2 | 6.2 | 7.1 | 5.1 | 4.0 | 2.0 | 1.8 | 1.3 | 3.8 | 4.9 | 5.4 | 6.0 | 3.9 | 1.3 | 2.8 |
| Tiotropium 18 Mcg Once Daily | -0.6 | 2.0 | 3.5 | 4.7 | 4.0 | 4.1 | 3.5 | 3.7 | 2.9 | 1.9 | 4.0 | 5.2 | 6.3 | 5.1 | 4.7 | 4.4 | 3.5 | 3.4 | 1.1 | 2.0 | 1.8 | 2.0 | 1.4 | -0.2 | 2.6 |
A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Participants (Number) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 50 |
| Tiotropium 18 Mcg Once Daily | 44 |
| Arformoterol /Tiotropium | 60 |
Analyzed from end of dosing to 12 hours. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Hours (Median) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.76 |
| Tiotropium 18 Mcg Once Daily | 1.29 |
| Arformoterol /Tiotropium | 0.39 |
Analyzed from end of dosing to 12 hours. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Hours (Median) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.39 |
| Tiotropium 18 Mcg Once Daily | 0.72 |
| Arformoterol /Tiotropium | 0.17 |
(NCT00424528)
Timeframe: Following 2 weeks of dosing
| Intervention | Liters (Mean) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.094 |
| Tiotropium 18 Mcg Once Daily | 0.054 |
| Arformoterol /Tiotropium | 0.217 |
A Greater than or Equal to 1 unit of Improvement in the TDI Focal Score is considered to be clinically important. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Percentage of participants (Number) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 66.67 |
| Tiotropium 18 Mcg Once Daily | 57.14 |
| Arformoterol /Tiotropium | 77.92 |
(NCT00424528)
Timeframe: 2 Weeks
| Intervention | Liters (Mean) | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 0: Immediately post first dose; N=76, 78, 78 | Week 0: 30 minutes post first dose; N=75, 78, 76 | Week 0: 1 hour post first dose; N=75, 78, 77 | Week 0: 2 hours post first dose; N=76, 78, 77 | Week 0: 4 hours post first dose; N=75, 77, 77 | Week 0: 6 hours post first dose; N=72, 74, 77 | Week 0: 8 hours post first dose; N=70, 73, 77 | Week 0: 10 hours post first dose; N=69, 71, 76 | Week 0: 12 hours post first dose; N=69, 71, 75 | Week 2: Immediately post first dose; N=71, 75, 74 | Week 2: 30 minutes post first dose; N=70, 74, 74 | Week 2: 1 hour post first dose; N=71, 75, 73 | Week 2: 2 hours post first dose; N=71, 73, 74 | Week 2: 4 hours post first dose; N=69, 72, 74 | Week 2: 6 hours post first dose; N=69, 72, 73 | Week 2: 8 hours post first dose; N=69, 70, 74 | Week 2: 10 hours post first dose; N=69, 71, 71 | Week 2: 12 hours post first dose; N=63, 67, 71 | Week 2: Immediately post second dose; N=65, 67, 72 | Week 2: 12.5 hours post first dose; N=65, 66, 72 | Week 2: 13 hours post first dose; N=63, 68, 72 | Week 2: 14 hours post first dose; N=65, 71, 72 | Week 2: 16 hours post first dose; N=63, 70, 71 | Week 2: 23 hours post first dose; N=70, 74, 74 | Week 2: 24 hours post first dose; N=69, 73, 74 | |
| Arformoterol /Tiotropium | 0.259 | 0.323 | 0.351 | 0.429 | 0.392 | 0.371 | 0.338 | 0.346 | 0.344 | 0.389 | 0.461 | 0.487 | 0.526 | 0.461 | 0.413 | 0.349 | 0.323 | 0.301 | 0.360 | 0.399 | 0.424 | 0.459 | 0.374 | 0.226 | 0.250 |
| Arformoterol 15 Mcg Twice Daily | 0.276 | 0.312 | 0.344 | 0.376 | 0.291 | 0.242 | 0.207 | 0.209 | 0.131 | 0.293 | 0.343 | 0.350 | 0.380 | 0.265 | 0.202 | 0.136 | 0.098 | 0.087 | 0.210 | 0.262 | 0.307 | 0.343 | 0.215 | 0.082 | 0.138 |
| Tiotropium 18 Mcg Once Daily | -0.031 | 0.122 | 0.197 | 0.248 | 0.206 | 0.195 | 0.159 | 0.175 | 0.146 | 0.055 | 0.203 | 0.224 | 0.290 | 0.221 | 0.209 | 0.214 | 0.158 | 0.124 | 0.034 | 0.087 | 0.082 | 0.110 | 0.098 | -0.011 | 0.115 |
Trough Inspiratory Capacity is defined as the measurement collected approximately 24 hours after the first in clinic double-blind treatment dose at week 0. Change is calculated as Week 2 24 hr post dose IC - Week 0 pre first dose IC. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Liters (Mean) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.074 |
| Tiotropium 18 Mcg Once Daily | 0.023 |
| Arformoterol /Tiotropium | 0.150 |
Trough FEV1 is defined as the measurement collected approximately 24 hours after the first in-clinic double-blind dose at Week 0. Change is calculated as Week 2 24 hour post first dose FEV1 - Week 0 pre-first dose FEV1. (NCT00424528)
Timeframe: Following 2 weeks of dosing
| Intervention | Liters (Mean) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.086 |
| Tiotropium 18 Mcg Once Daily | 0.080 |
| Arformoterol /Tiotropium | 0.154 |
Overall: Average of the levalbuterol usage in days per week over the 2 week period. Mean number of days/week=number of days levalbuterol used during time period, divided by number of days in the period, multiplied by 7. An actuation is one puff of levalbuterol. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Days per week (Mean) | |
|---|---|---|
| Baseline: Number of days used per week | Overall: Number of days used per week | |
| Arformoterol /Tiotropium | 4.57 | 1.38 |
| Arformoterol 15 Mcg Twice Daily | 4.44 | 2.16 |
| Tiotropium 18 Mcg Once Daily | 4.27 | 1.94 |
Overall: Average of the usage in number of actuations per day over the 2 week period. An actuation is one puff of levalbuterol. Mean number of actuations/day=number actuations used during time period, divided by number of days in time period. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Actuations per day (Mean) | |
|---|---|---|
| Baseline: Number of actuations per day | Overall: Number of actuations per day | |
| Arformoterol /Tiotropium | 3.08 | 0.68 |
| Arformoterol 15 Mcg Twice Daily | 3.24 | 1.18 |
| Tiotropium 18 Mcg Once Daily | 2.77 | 1.00 |
12 hour peak change in FEV1 is defined as maximum of the post dose changes through the nominal 12 hour assessment. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Liters (Mean) | |
|---|---|---|
| Week 0; N=76, 79, 78 | Week 2; N=71, 75, 74 | |
| Arformoterol /Tiotropium | 0.311 | 0.379 |
| Arformoterol 15 Mcg Twice Daily | 0.264 | 0.273 |
| Tiotropium 18 Mcg Once Daily | 0.218 | 0.265 |
(NCT00424528)
Timeframe: 0-12 hours following two weeks of dosing
| Intervention | Liters (Mean) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.118 |
| Tiotropium 18 Mcg Once Daily | 0.130 |
| Arformoterol /Tiotropium | 0.242 |
Baseline is FEV1 measurement collected prior to the first double-blind dose at week 0. Change defined as Week 0 FEV1 - Week 2 pre first dose FEV1. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Liters (Mean) | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 0: immediately post first dose; N=76, 78, 78 | Week 0: 30 minutes post first dose; N=75, 78, 76 | Week 0: 1 hour post first dose; N=75, 78, 77 | Week 0: 2 hours post first dose; N=76, 78, 77 | Week 0: 4 hours post first dose; N=75, 77, 77 | Week 0: 6 hours post first dose; N=72, 74, 77 | Week 0: 8 hours post first dose; N=70, 73, 77 | Week 0: 10 hours post first dose; N=69, 71, 76 | Week 0: 12 hours post first dose; N=69, 71, 75 | Week 2: immediately post first dose; N=71, 75, 74 | Week 2: 30 minutes post first dose; N=70, 74, 74 | Week 2: 1 hour post first dose; N=71, 75, 73 | Week 2: 2 hours post first dose; N=71, 73, 74 | Week 2: 4 hours post first dose; N=69, 72, 74 | Week 2: 6 hours post first dose; N=69, 72, 73 | Week 2: 8 hours post first dose; N=69, 70, 74 | Week 2: 10 hours post first dose; N=69, 71, 71 | Week 2: 12 hours post first dose; N=63, 67, 71 | Week 2: immediately post second dose; N=65, 67, 72 | Week 2: 12.5 hours post first dose; N=65, 66, 72 | Week 2: 13 hours post first dose; N=63, 68, 72 | Week 2: 14 hours post first dose; N=65, 71, 72 | Week 2: 16 hours post first dose; N=63, 70, 71 | Week 2: 23 hours post first dose; N=70, 74, 74 | Week 2: 24 hours post first dose; N=69, 73, 74 | |
| Arformoterol /Tiotropium | 0.139 | 0.183 | 0.189 | 0.239 | 0.223 | 0.214 | 0.194 | 0.190 | 0.199 | 0.240 | 0.280 | 0.308 | 0.330 | 0.279 | 0.266 | 0.220 | 0.205 | 0.189 | 0.235 | 0.270 | 0.272 | 0.292 | 0.240 | 0.145 | 0.154 |
| Arformoterol 15 Mcg Twice Daily | 0.132 | 0.163 | 0.182 | 0.193 | 0.155 | 0.128 | 0.102 | 0.101 | 0.044 | 0.154 | 0.188 | 0.185 | 0.213 | 0.154 | 0.123 | 0.067 | 0.054 | 0.035 | 0.115 | 0.143 | 0.159 | 0.182 | 0.114 | 0.040 | 0.086 |
| Tiotropium 18 Mcg Once Daily | -0.20 | 0.056 | 0.106 | 0.140 | 0.120 | 0.125 | 0.109 | 0.111 | 0.094 | 0.066 | 0.126 | 0.163 | 0.195 | 0.164 | 0.143 | 0.138 | 0.109 | 0.101 | 0.040 | 0.063 | 0.061 | 0.068 | 0.048 | -0.006 | 0.080 |
TDI Focal score (range -9 to 9) is defined as the sum of function impairment, magnitude of task, and magnitude of effort (each on a -3 to 3 scale). A score of -9 is maximum worsening and 9 is maximum improvement. (NCT00424528)
Timeframe: 2 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 2.28 |
| Tiotropium 18 Mcg Once Daily | 1.79 |
| Arformoterol /Tiotropium | 3.13 |
(NCT00424528)
Timeframe: 24 hours following two weeks of dosing.
| Intervention | Liters (Mean) |
|---|---|
| Arformoterol 15 Mcg Twice Daily | 0.104 |
| Tiotropium 18 Mcg Once Daily | 0.080 |
| Arformoterol /Tiotropium | 0.221 |
Mean Change from Baseline to Final Evaluation in the Per Protocol population assessed by Forced Expiratory Volume in 1 second. FEV1 is defined as the volume of air that can be forced out of the lungs in 1 second after taking a deep breath. (NCT00460577)
Timeframe: Baseline,4 hours
| Intervention | Liters (Mean) |
|---|---|
| Formoterol (Foradil®) | 0.32 |
| Fenoterol 0.5 mg + Berodual® | 0.34 |
Pharmacoeconomic analysis comparing the mean direct costs (total cost per prescription) of treatment with Formoterol (Foradil®) to treatment with Fenoterol 0.5 mg + Berodual®. (NCT00460577)
Timeframe: 4 hours
| Intervention | Cost in US Dollars (Mean) |
|---|---|
| Formoterol (Foradil®) | 9.21 |
| Fenoterol 0.5 mg + Berodual® | 25.67 |
Mean Change from Baseline to Final Evaluation in the Per Protocol population assessed by the Conway Clinical Scale. Assessment of the following: Wheezing, Accessory Muscle Use and Pulse Frequency in a 0 to 3 point scale according to severity for a minimum of 0 points and a total of 9 points in a very severe clinical case. (NCT00460577)
Timeframe: Baseline,4 hours
| Intervention | score on a scale (Mean) |
|---|---|
| Formoterol (Foradil®) | -3.18 |
| Fenoterol 0.5 mg + Berodual® | -3.04 |
Mean Change from Baseline to Final Evaluation in the Per Protocol population assessed by Pulse Oximetry used to monitor the percentage of oxygen saturation of hemoglobin in the blood. (NCT00460577)
Timeframe: Baseline, 4 hours
| Intervention | percentage (Mean) |
|---|---|
| Formoterol (Foradil®) | 2.57 |
| Fenoterol 0.5 mg + Berodual® | 2.83 |
Mean Change from Baseline to Final Evaluation in the Per Protocol population assessed by Maximum Expiratory Flow. (NCT00460577)
Timeframe: Baseline,4 hours
| Intervention | Liters/minute (Mean) |
|---|---|
| Formoterol (Foradil®) | 44 |
| Fenoterol 0.5 mg + Berodual® | 43.67 |
"Interim Analysis: Stage 1.~Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates." (NCT00463567)
Timeframe: Day 15, After 2 Weeks of treatment in Stage 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Indacaterol 150 µg | 1.49 |
| Indacaterol 300 µg | 1.52 |
| Tiotropium 18 µg | 1.45 |
| Placebo | 1.31 |
| Indacaterol 75 µg | 1.46 |
| Indacaterol 600 µg | 1.51 |
| Formoterol 12 µg | 1.42 |
"A Chronic Obstructive Pulmonary Disease (COPD) day of poor control was defined as any day in the participant's diary with a score ≥2 (moderate or severe) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness). Score for each symptom ranges from 0-3; a higher number indicates a more severe symptom. The model contained baseline percentage of days of poor control as well as FEV1 reversibility components as covariates." (NCT00463567)
Timeframe: up to 26 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Indacaterol 150 µg (Continued Into Stage 2) | 31.5 |
| Indacaterol 300 µg (Continued Into Stage 2) | 30.8 |
| Tiotropium (Continued Into Stage 2) | 31.0 |
| Placebo (Continued Into Stage 2) | 34.0 |
"Interim Analysis: Stage 1.~Spirometry was conducted according to internationally accepted standards. Standardized with respect to time (AUC 1h-4h) for FEV1 measurements taken from 1 hour to 4 hour post morning dose on Day 14. Standardized FEV1 AUC was calculated by the trapezoidal rule. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates." (NCT00463567)
Timeframe: Day 14, After 2 Weeks of treatment in Stage 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Indacaterol 150 µg | 1.53 |
| Indacaterol 300 µg | 1.58 |
| Tiotropium 18 µg | 1.49 |
| Placebo | 1.30 |
| Indacaterol 75 µg | 1.50 |
| Indacaterol 600 µg | 1.53 |
| Formoterol 12 µg | 1.52 |
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 h 10 min and the 23 h 45 min post dose values. Mixed model used baseline FEV1, FEV1 prior to and 30 minutes post inhalation of salbutamol/albuterol, and FEV1 prior to and 1 hour post inhalation of ipratropium as covariates. (NCT00463567)
Timeframe: after 12 weeks of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Indacaterol 150 µg (Continued Into Stage 2) | 1.46 |
| Indacaterol 300 µg (Continued Into Stage 2) | 1.46 |
| Tiotropium 18 µg (Continued Into Stage 2) | 1.42 |
| Placebo (Continued Into Stage 2) | 1.28 |
A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. Number of events per participant (NCT00463866)
Timeframe: 6 months.
| Intervention | Number of events per participant (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 0.0120 |
| Symbicort® SMART®) 2*2 | 0.0091 |
The total number of severe asthma exacerbations was calculated for each participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. (NCT00463866)
Timeframe: 6 months.
| Intervention | Fraction of participants with event (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 0.09686 |
| Symbicort® SMART®) 2*2 | 0.07955 |
The number of as-needed inhalations was measured 2 times during 2 weeks before 13 weeks and 26 weeks of treatment. (NCT00463866)
Timeframe: 4 weeks
| Intervention | Inhalations per day per participant (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 0.897 |
| Symbicort® SMART®) 2*2 | 0.625 |
The ACQ5 was used. The lower value the better with a full range from 0=no impairment, 6= maximum impairment. Awakenings, morning symptoms, limitations, shortness of breath and wheeze. (NCT00463866)
Timeframe: 6 months.
| Intervention | Scores in a scale (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 1.18 |
| Symbicort® SMART®) 2*2 | 1.089 |
Time to first severe asthma exacerbation, translated to mean number of severe asthma exacerbations per participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. (NCT00463866)
Timeframe: 6 months
| Intervention | Severe exacerbations per participant (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 0.097 |
| Symbicort® SMART®) 2*2 | 0.080 |
The mean percent of participants fulfilling the criteria for a well controlled asthma week in each treatment. A well controlled asthma week is defined as a week with no exacerbations and no night-time awakenings due to asthma and a maximum of 2 days with symptoms and as-needed inhalation use. (NCT00463866)
Timeframe: 6 months.
| Intervention | Percentage of participants (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 43.69 |
| Symbicort® SMART®) 2*2 | 54.26 |
The mean total daily dose of steroids from Symbicort was calculated as the sum of the maintenance dose and the as-needed dose. (NCT00463866)
Timeframe: 4 weeks
| Intervention | μg budesonide per day (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 462.96 |
| Symbicort® SMART®) 2*2 | 736.58 |
Total number of days with oral/systemic glucocorticosteroids during severe exacerbation calculated for each participant. A severe asthma exacerbation is defined as deterioration in asthma requiring oral/systemic glucocorticosteroids for at least 3 days and/or hospitalisation/emergency room visit with oral/systemic glucocorticosteroid treatment. (NCT00463866)
Timeframe: 6 months.
| Intervention | Days per participant (Mean) |
|---|---|
| Symbicort® SMART®) 1*2 | 9.6 |
| Symbicort® SMART®) 2*2 | 9.1 |
The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). (NCT00489853)
Timeframe: Single measurement performed after exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 11.5 |
| Formoterol | 11.6 |
| Placebo | 11.4 |
The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any discomfort) to 4 (almost constant discomfort). (NCT00489853)
Timeframe: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
| Intervention | Score on a scale (Mean) |
|---|---|
| Symbicort | -0.08 |
| Formoterol | -0.02 |
| Placebo | 0.17 |
The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). (NCT00489853)
Timeframe: Single measurement performed at rest prior to exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 3.6 |
| Formoterol | 3.4 |
| Placebo | 3.9 |
The Borg CR10 Scale consists of 10-point score that the patients pointed to so as to indicate their level of dyspnea before and during exercise testing (where 0 indicates no breathlessness at all and 10 indicates maximum breathlessness. Patients are allowed to assign an even higher number depending on their perceived level of breathlessness). (NCT00489853)
Timeframe: Single measurement performed at rest prior to exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 3.3 |
| Formoterol | 3.4 |
| Placebo | 3.9 |
The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of coughing) to 4 (never free of need to cough). (NCT00489853)
Timeframe: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.11 |
| Formoterol | -0.05 |
| Placebo | 0.10 |
Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods. (NCT00489853)
Timeframe: Single measurement taken1 hour post-dose at the end of each 1-week treatment period
| Intervention | Seconds (Mean) |
|---|---|
| Symbicort | 529 |
| Formoterol | 441 |
| Placebo | 406 |
Treatment means from individual patient data. Patients with only one EET value where excluded since this model, with patient and period as fixed factors, required data from at least two periods. (NCT00489853)
Timeframe: Single measurement taken 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Seconds (Mean) |
|---|---|
| Symbicort | 463 |
| Formoterol | 408 |
| Placebo | 388 |
The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment. (NCT00489853)
Timeframe: Pre-dose at the start of treatment and pre-dose after one week of treatment
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.0830 |
| Formoterol | 0.0630 |
| Placebo | -0.046 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Liters (Median) |
|---|---|
| Symbicort | 5.59 |
| Formoterol | 5.66 |
| Placebo | 5.79 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 2.12 |
| Formoterol | 2.12 |
| Placebo | 1.85 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 5.47 |
| Formoterol | 5.49 |
| Placebo | 5.82 |
The change in average daily use for the run-in or wash-out period to the average daily use of the subsequent treatment period. (NCT00489853)
Timeframe: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
| Intervention | Number of inhalations during 24 hours (Mean) |
|---|---|
| Symbicort | -0.42 |
| Formoterol | -0.36 |
| Placebo | 0.51 |
The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment. (NCT00489853)
Timeframe: Pre-dose at the start of treatment and pre-dose after one week of treatment
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.060 |
| Formoterol | 0.067 |
| Placebo | -0.094 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1hour post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 2.19 |
| Formoterol | 2.18 |
| Placebo | 1.91 |
The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period. (NCT00489853)
Timeframe: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort | 1.30 |
| Formoterol | 5.60 |
| Placebo | -10.00 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 4.83 |
| Formoterol | 4.94 |
| Placebo | 5.13 |
The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (unaware of any difficulty in breathing) to 4 (almost constant difficulties in breathing). All patients with data from both periods are included. (NCT00489853)
Timeframe: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
| Intervention | Score on Scale (Mean) |
|---|---|
| Symbicort | -0.12 |
| Formoterol | -0.40 |
| Placebo | 0.15 |
Score from a questionnaire, with scores ranging form 0 (perfect health) to 100 (worst possible state). Includes all patients with data. (NCT00489853)
Timeframe: Single measurement taken at the end of each 1-week treatment period
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 51.7 |
| Formoterol | 51.6 |
| Placebo | 54.5 |
The change in average value for the run-in or wash-out period to the average value of the subsequent treatment period, with an ordinal scale of 0 (symptoms did not cause a sleep problem) to 4 (did not sleep at all due to symptoms). (NCT00489853)
Timeframe: Daily diary data entered during the 1-week run-in or wash-out period and the subsequent 1-week treatment period
| Intervention | Score on Scale (Mean) |
|---|---|
| Symbicort | -1.70 |
| Formoterol | -0.03 |
| Placebo | 0.11 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | kilopascal (Mean) |
|---|---|
| Symbicort | 2.90 |
| Formoterol | 2.98 |
| Placebo | 4.22 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Kilopascals (Mean) |
|---|---|
| Symbicort | 3.06 |
| Formoterol | 3.20 |
| Placebo | 4.12 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Liter (Mean) |
|---|---|
| Symbicort | 7.58 |
| Formoterol | 7.62 |
| Placebo | 7.45 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 7.41 |
| Formoterol | 7.37 |
| Placebo | 7.63 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 2.75 |
| Formoterol | 2.73 |
| Placebo | 2.37 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 2.69 |
| Formoterol | 2.64 |
| Placebo | 2.42 |
The mean of the changes for each patient between the pre-dose value at the start of treatment and the pre-dose value after one week of treatment. (NCT00489853)
Timeframe: Pre-dose at the start of treatment and pre-dose after one week of treatment
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.105 |
| Formoterol | 0.089 |
| Placebo | -0.083 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 2.14 |
| Formoterol | 2.08 |
| Placebo | 1.92 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 1 hour post-dose at the end of each 1-week treatment period
| Intervention | Liter (Mean) |
|---|---|
| Symbicort | 2.06 |
| Formoterol | 2.10 |
| Placebo | 1.97 |
The level of breathing discomfort experienced by patients, on a scale of 0 (no breathing discomfort at all) to >10 (absolute maximum breathing discomfort). All patients with data are included. (NCT00489853)
Timeframe: Single measurement performed after exercise endurance test performed 6 hours post-dose at the end of each 1-week treatment period
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 11.5 |
| Formoterol | 11.5 |
| Placebo | 11.8 |
Treatment means from individual participant data. (NCT00489853)
Timeframe: Single measurement obtained before exercise endurance test performed 6 hous post-dose at the end of each 1-week treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 4.74 |
| Formoterol | 4.79 |
| Placebo | 5.19 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The CDLM questionnaire is as a questionnaire to report on patient's ability to carry out each of six different morning activities (score ranging from 0 not performed to 1performed) and rank the difficulty of performing each of those activities (score ranging from 0 so difficult that the activity could not be carried out by the patient on their own to 5 activity was not at all difficult to carry out. Total score for each morning activity range from 0-6. Total score for whole CDLM questionnaire range from 0-36." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.202 |
| Placebo+Tiotropium | 0.07 |
Change in the 5 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.266 |
| Placebo+Tiotropium | 0.106 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.054 |
| Placebo+Tiotropium | -0.046 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.209 |
| Placebo+Tiotropium | 0.014 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.169 |
| Placebo+Tiotropium | -0.018 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 20.4 |
| Placebo+Tiotropium | 5.2 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 16.71 |
| Placebo+Tiotropium | 1.1 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 5.12 |
| Placebo+Tiotropium | -3.52 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.91 |
| Placebo+Tiotropium | 0.97 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 1.0 |
| Placebo+Tiotropium | 1.0 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 1.0 |
| Placebo+Tiotropium | 1.0 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.95 |
| Placebo+Tiotropium | 0.95 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.97 |
| Placebo+Tiotropium | 0.98 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 1.0 |
| Placebo+Tiotropium | 1.0 |
Ratio of treatment period mean to run-in value (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Ratio (Median) |
|---|---|
| Symbicort+Tiotropium | 0.96 |
| Placebo+Tiotropium | 0.99 |
Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation (NCT00496470)
Timeframe: 12 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort+Tiotropium | 25 |
| Placebo+Tiotropium | 61 |
"Change in total score from baseline (Visit 3) to end of treatment (Visit 6, or last available visit).~SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life." (NCT00496470)
Timeframe: Baseline and 12 weeks
| Intervention | Score on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -4.12 |
| Placebo+Tiotropium | -1.99 |
Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.745 |
| Placebo+Tiotropium | -0.371 |
Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.417 |
| Placebo+Tiotropium | -0.124 |
Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.279 |
| Placebo+Tiotropium | 0.022 |
Daily diary record - Total, 24 hours, during the night, and during the day. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| Symbicort+Tiotropium | -1.024 |
| Placebo+Tiotropium | -0.347 |
Change in the pre-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.078 |
| Placebo+Tiotropium | 0.014 |
Change in the 60 min post-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.26 |
| Placebo+Tiotropium | 0.149 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.143 |
| Placebo+Tiotropium | -0.006 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.325 |
| Placebo+Tiotropium | -0.202 |
"Daily diary record. Change in average values from run-in to the full treatment period.~The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions." (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.404 |
| Placebo+Tiotropium | -0.28 |
Change in the pre-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.07 |
| Placebo+Tiotropium | 0.014 |
Change in the 60 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12 (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.353 |
| Placebo+Tiotropium | 0.19 |
Change in the pre-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.064 |
| Placebo+Tiotropium | -0.001 |
Change in the 60 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.214 |
| Placebo+Tiotropium | 0.083 |
Change in the 5 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12) (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.165 |
| Placebo+Tiotropium | 0.042 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort+Tiotropium | 2.82 |
| Placebo+Tiotropium | -5.54 |
Daily diary record. Change in average values from run-in to the full treatment period (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort+Tiotropium | 0.012 |
| Placebo+Tiotropium | -0.065 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.197 |
| Placebo+Tiotropium | -0.045 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.246 |
| Placebo+Tiotropium | -0.079 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.184 |
| Placebo+Tiotropium | -0.061 |
Daily diary record. Change in average values from run-in to the full treatment period. Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe (NCT00496470)
Timeframe: Baseline to 12 weeks
| Intervention | Units on a Scale (Mean) |
|---|---|
| Symbicort+Tiotropium | -0.177 |
| Placebo+Tiotropium | -0.049 |
Change in average value from the run-in to the treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation. Missing data between the first and last entry were estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Liters/min (Mean) |
|---|---|
| With Spacer | 27.00 |
| Without Spacer | 15.30 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| With Spacer | -0.21 |
| Without Spacer | -0.14 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Inhalations (Mean) |
|---|---|
| With Spacer | -0.30 |
| Without Spacer | -0.19 |
Ratio between the value at the end of treatment and the value at start of treatment, including only patients with values at both baseline and end of treatment (NCT00536913)
Timeframe: At baseline and 4 weeks
| Intervention | Ratio (Geometric Mean) |
|---|---|
| With Spacer | 0.86 |
| Without Spacer | 1.03 |
Change in Percentage of nights with awakenings, average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Percentage of nights (Mean) |
|---|---|
| With Spacer | -13.80 |
| Without Spacer | -8.20 |
Change in average value from the run-in to the treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry were estimated using linear interpolation. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Liters/min (Mean) |
|---|---|
| With Spacer | 28.70 |
| Without Spacer | 19.50 |
Changes in FEV1 from baseline to the mean value at 2 weeks to 4 weeks with the baseline value as a covariate. (NCT00536913)
Timeframe: At baseline, at 2 weeks and 4 weeks
| Intervention | Liters (Mean) |
|---|---|
| With Spacer | 0.17 |
| Without Spacer | 0.14 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| With Spacer | -0.25 |
| Without Spacer | -0.28 |
Change in average value from the run-in to treatment period, calculated using all available data for the 10 last days of run-in, and all available data after randomisation.Missing data between the first and last entry estimated using linear interpolation. Daily scale:0 = No symptoms; 1 = Mild symptoms; 2 = Moderate symptoms; 3 = Severe symptoms. (NCT00536913)
Timeframe: Daily during run-in and daily during treatment period of 6 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| With Spacer | -0.20 |
| Without Spacer | -0.21 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.21 |
| Seretide Diskus | 0.14 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1920 |
| Seretide Diskus First | 0.1240 |
The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (run-in, and washout) and day 1 of treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0950 |
| Seretide Diskus | 0.0490 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0160 |
| Seretide Diskus | 0.0030 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1220 |
| Seretide Diskus | 0.1030 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0930 |
| Seretide Diskus | 0.0280 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 11.6 |
| Seretide Diskus | 6.1 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 6 with 0=worst and 6 = best. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.24 |
| Seretide Diskus | 0.19 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1470 |
| Seretide Diskus | 0.1060 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.0310 |
| Seretide Diskus | 0.0590 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minutes (Mean) |
|---|---|
| Symbicort Turbuhaler | 4.8 |
| Seretide Diskus | 7.9 |
The change from baseline in PEF was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 15.1 |
| Seretide Diskus | 13.4 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 19.9 |
| Seretide Diskus | 16.7 |
The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort Turbuhaler | 4 |
| Seretide Diskus | 1.8 |
The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (run-in, and washout) and day 1 of treatment period
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.1120 |
| Seretide Diskus | 0.0440 |
The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate. (NCT00542880)
Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
| Intervention | Liters (Mean) |
|---|---|
| Symbicort Turbuhaler | 15.8 |
| Seretide Diskus | 9.6 |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1, which is taken as the maximum FEV1 recorded post-dose. (NCT00545272)
Timeframe: Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose
| Intervention | minutes (Mean) | |
|---|---|---|
| Day 1 [N=61, 68, 65, 71, 64, 62] | Day 14 [N=61, 66, 64, 70, 62, 59] | |
| Formoterol | 105.6 | 114.6 |
| Indacaterol 125 μg | 109.6 | 118.7 |
| Indacaterol 250 μg | 119.0 | 96.7 |
| Indacaterol 500 μg | 116.2 | 114.0 |
| Indacaterol 62.5 μg | 91.0 | 103.8 |
| Placebo | 90.5 | 80.4 |
FEV1 was measured on Day 14 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00545272)
Timeframe: Day 14, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 2.670 |
| Indacaterol 125 μg | 2.698 |
| Indacaterol 250 μg | 2.772 |
| Indacaterol 500 μg | 2.786 |
| Formoterol | 2.821 |
| Placebo | 2.565 |
Participants recorded the use of rescue medications (salbutamol/albuterol) for treatment of asthma symptoms twice a day in a diary during the 14 days of the treatment period. (NCT00545272)
Timeframe: Over 14 days
| Intervention | participants (Number) | |
|---|---|---|
| Night | Day | |
| Formoterol | 31 | 30 |
| Indacaterol 125 μg | 40 | 43 |
| Indacaterol 250 μg | 36 | 28 |
| Indacaterol 500 μg | 34 | 35 |
| Indacaterol 62.5 μg | 36 | 33 |
| Placebo | 40 | 39 |
The Peak Expiratory Flow (PEF) rate is the maximal rate that a person can exhale during a short maximal expiratory effort after fully inhaling. Participants measured their PEF using a peak flow meter and recorded measurements in a diary every morning and evening during the study, prior to taking study medication. Change from baseline is the difference between the mean baseline PEF recorded during the screening period until the first day of treatment, and the overall mean PEF from Days 1 to 14. (NCT00545272)
Timeframe: Baseline (recorded during the screening period) and Days 1-14 (treatment period)
| Intervention | liters/minute (Mean) | |
|---|---|---|
| Morning [N=56, 61, 53, 63, 57, 48] | Evening [N=56, 58, 54, 59, 55, 47] | |
| Formoterol | 25.2 | 26.2 |
| Indacaterol 125 μg | 17.2 | 4.2 |
| Indacaterol 250 μg | 25.7 | 18.4 |
| Indacaterol 500 μg | 25.8 | 25.8 |
| Indacaterol 62.5 μg | 18.7 | 5.9 |
| Placebo | -4.3 | -11.4 |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00545272)
Timeframe: Day 1 Baseline (prior to first dose) and 24 hours post-dose.
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 0.054 |
| Indacaterol 125 μg | 0.081 |
| Indacaterol 250 μg | 0.143 |
| Indacaterol 500 μg | 0.141 |
| Formoterol | 0.155 |
| Placebo | 0.010 |
FEV1 was measured on Day 1 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00545272)
Timeframe: Day 1, pre-dose, 5, 20 and 30 minutes, 1, 2, 3, and 4 hours post-dose.
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 2.668 |
| Indacaterol 125 μg | 2.687 |
| Indacaterol 250 μg | 2.726 |
| Indacaterol 500 μg | 2.753 |
| Formoterol | 2.832 |
| Placebo | 2.547 |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00545272)
Timeframe: Baseline (prior to first dose) and Day 15 (24 hours after last dose)
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 0.039 |
| Indacaterol 125 μg | 0.054 |
| Indacaterol 250 μg | 0.124 |
| Indacaterol 500 μg | 0.166 |
| Formoterol | 0.075 |
| Placebo | -0.018 |
Participants recorded the use of rescue medications (salbutamol/albuterol) for treatment of asthma symptoms twice a day in a diary during the 14 days of the treatment period. (NCT00557466)
Timeframe: Over 14 days
| Intervention | participants (Number) | |
|---|---|---|
| Day | Night | |
| Formoterol | 65 | 67 |
| Indacaterol 125 μg | 61 | 60 |
| Indacaterol 250 μg | 73 | 67 |
| Indacaterol 500 μg | 65 | 59 |
| Indacaterol 62.5 μg | 74 | 72 |
| Placebo | 70 | 72 |
The Peak Expiratory Flow (PEF) rate is the maximal rate that a person can exhale during a short maximal expiratory effort after fully inhaling. Participants measured their PEF using a peak flow meter prior to taking study medication and recorded measurements in a diary every morning and evening during the study. Change from baseline is the difference between the mean baseline PEF recorded during the screening period until the first day of treatment, and the overall mean PEF from Days 1 to 14. (NCT00557466)
Timeframe: Baseline (recorded during the screening period) and Days 1-14 (treatment period).
| Intervention | liters/minute (Mean) | |
|---|---|---|
| Morning [N=56, 63, 59, 54, 54, 55] | Evening [N=56, 58, 56, 49, 48, 52] | |
| Formoterol | 16.06 | 14.97 |
| Indacaterol 125 μg | 19.91 | 13.42 |
| Indacaterol 250 μg | 23.63 | 19.00 |
| Indacaterol 500 μg | 11.11 | 5.92 |
| Indacaterol 62.5 μg | 3.10 | -2.72 |
| Placebo | -4.24 | -2.75 |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 1 day of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00557466)
Timeframe: Day 1 Baseline (prior to first dose) and 24 hours post-dose.
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 0.028 |
| Indacaterol 125 μg | 0.054 |
| Indacaterol 250 μg | 0.060 |
| Indacaterol 500 μg | 0.073 |
| Formoterol | 0.140 |
| Placebo | -0.009 |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00557466)
Timeframe: Baseline (prior to first dose) and Day 15 (24 hours after last dose)
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 0.051 |
| Indacaterol 125 μg | 0.073 |
| Indacaterol 250 μg | 0.076 |
| Indacaterol 500 μg | 0.121 |
| Formoterol | 0.098 |
| Placebo | 0.005 |
FEV1 was measured on Day 1 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00557466)
Timeframe: Day 1; pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose.
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 1.371 |
| Indacaterol 125 μg | 1.422 |
| Indacaterol 250 μg | 1.427 |
| Indacaterol 500 μg | 1.438 |
| Formoterol | 1.535 |
| Placebo | 1.321 |
FEV1 was measured on Day 14 pre-dose and up to 4 hours post-dose. The Area Under the Curve (AUC) for FEV1 was analyzed using Analysis of Covariance adjusting for treatment and region with baseline FEV1 as a covariate. (NCT00557466)
Timeframe: Day 14, pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose.
| Intervention | liters (Least Squares Mean) |
|---|---|
| Indacaterol 62.5 μg | 1.407 |
| Indacaterol 125 μg | 1.461 |
| Indacaterol 250 μg | 1.441 |
| Indacaterol 500 μg | 1.500 |
| Formoterol | 1.541 |
| Placebo | 1.315 |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Time to peak FEV1 is calculated in minutes from the time of inhalation of study drug to the time of the peak FEV1, which is taken as the maximum FEV1 recorded post-dose. (NCT00557466)
Timeframe: Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose
| Intervention | minutes (Mean) | |
|---|---|---|
| Day 1 [N=98, 91, 97, 91, 87, 87] | Day 14 [N=93, 86, 90, 89, 83, 82] | |
| Formoterol | 115.0 | 89.1 |
| Indacaterol 125 μg | 84.4 | 105.6 |
| Indacaterol 250 μg | 101.4 | 104.7 |
| Indacaterol 500 μg | 105.3 | 116.4 |
| Indacaterol 62.5 μg | 80.9 | 91.3 |
| Placebo | 85.7 | 68.0 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change in FEV1 from pre-dose to the readings taken 12 hours post-dose, and reports the largest change during that time. (NCT00571428)
Timeframe: 12 hours
| Intervention | liters (Mean) |
|---|---|
| 15 Mcg BID | 0.269 |
| 30 Mcg QD | 0.324 |
Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration. (NCT00571428)
Timeframe: pre-dose, immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose
| Intervention | minutes (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-dose (n=32,32) | Immediately post first dose (n=32,33) | 30 minutes post first dose (n=33,33) | 1 hour post first dose (n=33,33) | 2 hours post first dose (n=33,33) | 4 hours post first dose (n=33,33) | 6 hours post first dose (n=32,30) | 8 hours post first dose (n=32,30) | 10 hours post first dose (n=31,30) | 12 hours post first dose (n=30,32) | 12.5 hours post first dose (n=30,32) | 13 hours post first dose (n=30,32) | 14 hours post first dose (n=30,32) | 16 hours post first dose (n=32,33) | 23 hours post first dose (n=30,32) | 24 hours post first dose (n=31,32) | |
| 15 Mcg BID | 2.545 | 2.838 | 2.903 | 2.918 | 2.931 | 2.871 | 2.849 | 2.776 | 2.796 | 2.702 | 2.852 | 2.905 | 2.878 | 2.854 | 2.733 | 2.774 |
| 30 Mcg QD | 2.601 | 2.905 | 2.953 | 3.003 | 3.030 | 3.028 | 2.993 | 2.940 | 2.906 | 2.797 | 2.796 | 2.815 | 2.813 | 2.812 | 2.700 | 2.763 |
Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the percent of the estimated healthy lung function at specified time points. (NCT00571428)
Timeframe: Pre-dose, Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
| Intervention | Percent of Predicted FEV1 (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-dose (n=32,32) | Immediately post first dose (n=32,33) | 30 min post first dose (n=33,33) | 1 hour post first dose (n=33,33) | 2 hours post first dose (n=33,33) | 4 hours post first dose (n=33,33) | 6 hours post first dose (n=32,30) | 8 hours post first dose (n=32,30) | 10 hours post first dose (n=31,30) | 12 hours post first dose (n=30,32) | 12.5 hours post dose (n=30,32) | 13 hours post first dose (n=30,32) | 14 hours post first dose (n=30,32) | 16 hours post first dose (n=32,33) | 23 hours post first dose (n=30,32) | 24 hours post first dose (n=31,32) | |
| 15 Mcg BID | 40.717 | 45.504 | 45.990 | 46.456 | 47.136 | 45.839 | 46.294 | 44.534 | 44.913 | 43.885 | 46.935 | 47.848 | 48.051 | 46.977 | 44.876 | 44.844 |
| 30 Mcg QD | 40.784 | 46.396 | 47.303 | 47.816 | 48.559 | 48.832 | 48.133 | 46.491 | 46.360 | 45.446 | 45.560 | 45.723 | 45.711 | 45.599 | 42.793 | 43.729 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome offers the FEV1 readings taken pre-dose and at various time points within 24 hours post-dose. (NCT00571428)
Timeframe: pre-dose, immediately post-dose, 30 min, 1,2,4,6,8,10,12, 12.5,13,14,16,23,24 hours post first dose
| Intervention | liters (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pre-dose (n=32,32) | Immediately post first dose (n=32,33) | 30 minutes (n=33,33) | 1 hour post first dose (n=33,33) | 2 hours post first dose (n=33,33) | 4 hours post first dose (n=33,33) | 6 hours post first dose (n=32,30) | 8 hours post first dose (n=32,30) | 10 hours post first dose (n=31,30) | 12 hours post first dose (n=30,32) | 12.5 hours post first dose (n=30,32) | 13 hours post first dose (n=30,32) | 14 hours post first dose (n=30,32) | 16 hours post first dose (n=32,33) | 23 hours post first dose (n=30,32) | 24 hours post first dose (n=31,32) | |
| 15 Mcg BID | 1.184 | 1.332 | 1.349 | 1.362 | 1.378 | 1.342 | 1.359 | 1.303 | 1.308 | 1.270 | 1.359 | 1.389 | 1.397 | 1.368 | 1.297 | 1.296 |
| 30 Mcg QD | 1.179 | 1.358 | 1.384 | 1.401 | 1.419 | 1.429 | 1.414 | 1.373 | 1.371 | 1.327 | 1.332 | 1.330 | 1.337 | 1.344 | 1.252 | 1.279 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome offers the change in FEV1 readings between pre-dose and various time points within 24 hours post-dose. (NCT00571428)
Timeframe: Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
| Intervention | liters (Mean) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Immediately post first dose (n=32,32) | 30 minutes post first dose (n=32,32) | 1 hour post first dose (n=32,32) | 2 hours post first dose (n=32,32) | 4 hours post first dose (n=32,32) | 6 hours post first dose (n=32,30) | 8 hours post first dose (n=32,30) | 10 hours post first dose (n=30,30) | 12 hours post first dose (n=30,32) | 12.5 hours post first dose (n=30,32) | 13 hours post first dose (n=30,32) | 14 hours post first dose (n=30,32) | 16 hours post first dose (32,32) | 23 hours post first dose (n=30,31) | 24 hours post first dose (n=31,31) | |
| 15 Mcg BID | 0.148 | 0.168 | 0.179 | 0.193 | 0.161 | 0.175 | 0.119 | 0.145 | 0.105 | 0.193 | 0.223 | 0.232 | 0.184 | 0.132 | 0.144 |
| 30 Mcg QD | 0.187 | 0.211 | 0.229 | 0.243 | 0.248 | 0.243 | 0.202 | 0.200 | 0.148 | 0.153 | 0.151 | 0.158 | 0.163 | 0.088 | 0.120 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken within 24 hours of dosing. (NCT00571428)
Timeframe: 0-24 hours post dose
| Intervention | liters (Mean) |
|---|---|
| 15 Mcg BID | 0.156 |
| 30 Mcg QD | 0.173 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken within 12 hours of dosing. (NCT00571428)
Timeframe: 0-12 hours
| Intervention | liters (Mean) |
|---|---|
| 15 Mcg BID | 0.148 |
| 30 Mcg QD | 0.214 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change from pre-dose for a series of FEV1 readings taken between 12 and 24 hours of dosing. (NCT00571428)
Timeframe: 12-24 hours
| Intervention | liters (Mean) |
|---|---|
| 15 Mcg BID | 0.179 |
| 30 Mcg QD | 0.132 |
Time to a 12 percent improvement in forced expiratory volume in one second (FEV1) AND a 200 milliliter increase in FEV1 within 12 hours of dosing. Only patients who met both conditions are included (NCT00571428)
Timeframe: up to 12 hours post dose
| Intervention | minutes (Median) |
|---|---|
| 15 Mcg BID | 12.62 |
| 30 Mcg QD | 2.86 |
Time to a 15 percent improvement in forced expiratory volume in one second (FEV1) within 12 hours of dosing. Only patients who achieved at least a 15 percent improvement are included. (NCT00571428)
Timeframe: 12 hours post first dose
| Intervention | minutes (Median) |
|---|---|
| 15 Mcg BID | 7.75 |
| 30 Mcg QD | 2.43 |
Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the percent of the estimated healthy lung function and reports the highest percent found within 12 hours of dosing. (NCT00571428)
Timeframe: 12 hours
| Intervention | percent of predicted FEV1 (Mean) |
|---|---|
| 15 Mcg BID | 49.399 |
| 30 Mcg QD | 51.251 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. This outcome measures the change in FEV1 from pre-dose to the readings taken 24 hours post-dose, which represents the trough in dose level. (NCT00571428)
Timeframe: pre-dose and 24 hours post-dose
| Intervention | liters (Mean) |
|---|---|
| 15 Mcg BID | 0.144 |
| 30 Mcg QD | 0.120 |
Predicted FEV1 is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. This outcome uses actual FEV1 readings to generate the change in percent of the estimated healthy lung function at specified time points compared to the pre-dose value. (NCT00571428)
Timeframe: Immediately post first dose, 30 min, 1,2,4,6,8,10,12,12.5,13,14,16,23,24 hours post first dose
| Intervention | percent of predicted FEV1 (Mean) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Immediately post first dose (n=32,32) | 30 minutes post first dose (n=32,32) | 1 hour post first dose (n=32,32) | 2 hours post first dose (n=32,32) | 4 hours post first dose (n=32,32) | 6 hours post first dose (n=32,30) | 8 hours post first dose (n=32,30) | 10 hours post first dose (n=30,30) | 12 hours post first dose (n=30,32) | 12.5 hours post first dose (n=30,32) | 13 hours post first dose (n=30,32) | 14 hours post first dose (n=30,32) | 16 hours post first dose (n=32,32) | 23 hours post first dose (n=30,31) | 24 hours post first dose (n=31,31) | |
| 15 Mcg BID | 4.787 | 5.574 | 5.980 | 6.570 | 5.399 | 5.576 | 3.816 | 4.810 | 3.507 | 6.557 | 7.470 | 7.672 | 6.259 | 4.498 | 4.875 |
| 30 Mcg QD | 6.028 | 6.917 | 7.437 | 8.055 | 8.189 | 7.904 | 6.261 | 6.130 | 4.662 | 4.776 | 4.939 | 4.927 | 4.937 | 2.457 | 3.528 |
Forced vital capacity is the total amount of air that can forcibly be blown out after full inspiration. The measure compares the change from pre-dose reading to each post-dose time point. (NCT00571428)
Timeframe: immediately post first dose, 30 min, 1,2,4,6,8,10,12, 12.5, 13, 14, 16, 23,24 hours post first dose
| Intervention | liters (Mean) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Immediately post first dose (n=32,32) | 30 minutes post first dose (n=32,32) | 1 hour post first dose (n=32,32) | 2 hours post first dose (n=32,32) | 4 hours post first dose (n=32,32) | 6 hours post first dose (n=32,30) | 8 hours post first dose (n=32,30) | 10 hours post first dose (n=30,30) | 12 hours post first dose (n=30,32) | 12.5 hours post first dose (n=30,32) | 13 hours post first dose (n=30,32) | 14 hours post first dose (n=30,32) | 16 hours post first dose (n=32,32) | 23 hours post first dose (n=30,31) | 24 hours post first dose (n=31,31) | |
| 15 Mcg BID | 0.293 | 0.334 | 0.352 | 0.355 | 0.296 | 0.304 | 0.231 | 0.246 | 0.175 | 0.325 | 0.378 | 0.351 | 0.308 | 0.206 | 0.257 |
| 30 Mcg QD | 0.290 | 0.340 | 0.390 | 0.411 | 0.398 | 0.384 | 0.331 | 0.297 | 0.196 | 0.195 | 0.214 | 0.213 | 0.183 | 0.088 | 0.148 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. Change in FEV1 was calculated as postdose value minus the predose value at each visit. (NCT00583947)
Timeframe: predose, various postdose timepoints
| Intervention | liters (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 10 minutes post dose 1 (n=37,38,27) | 25 minutes post dose 1 (n=37,37,27) | 10 minutes post dose 2 (n=36,38,27) | 25 minutes post dose 2 (n=36,38,27) | 10 minutes post dose 3 (n=34,38,27) | 25 minutes post dose 3 (n=35,38,26) | 2 hours post dose 1 (n=36,37,27) | 4 hours post dose 1 (n=36,38,27) | 6 hours post dose 1 (n=36,38,27) | |
| Arformoterol 15 Mcg | 0.133 | 0.158 | 0.175 | 0.183 | 0.203 | 0.205 | 0.218 | 0.198 | 0.174 |
| Arformoterol 7.5 Mcg | 0.117 | 0.142 | 0.169 | 0.162 | 0.179 | 0.188 | 0.194 | 0.170 | 0.173 |
| Levalbuterol 0.63 mg | 0.160 | 0.159 | 0.199 | 0.194 | 0.226 | 0.226 | 0.216 | 0.163 | 0.098 |
Diastolic blood pressure measured at various timepoints: predose and timepoints after each of the three dosings. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes). (NCT00583947)
Timeframe: predose, various timeframes up to 5 hours post last dose
| Intervention | mmHg (Mean) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Predose (n=51,52,40) | 15 min post dose 1 (n=51,52,40) | 30 min post dose 1 (n=51,52,40) | 60 min post dose 1 (n=51,51,40) | 15 min post dose 2 (n=50,51,40) | 30 min post dose 2 (n=47,50,40) | 60 min post dose 2 (n=46,50,37) | 30 min post last dose (n=49,52,40) | 60 min post last dose (n=49,52,40) | 1.5 hours post last dose (n=48,52,40) | 2 hours post last dose (n=50,52,40) | 2.5 hours post last dose (n=49,52,40) | 3 hours post last dose (n=50,52,40) | 3.5 hours post last dose (n=50,52,40) | 4 hours post last dose (n=50,52,40) | 4.5 hours post last dose (n=50,52,40) | 5 hours post last dose (n=50,52,40) | |
| Arformoterol 15 Mcg | 63.6 | 62.5 | 61.6 | 62.3 | 60.8 | 61.7 | 62.3 | 61.6 | 62.5 | 62.5 | 62.1 | 62.3 | 62.5 | 62.6 | 59.9 | 61.9 | 60.0 |
| Arformoterol 7.5 Mcg | 63.2 | 62.0 | 62.5 | 62.5 | 63.3 | 62.2 | 62.0 | 62.0 | 62.1 | 62.3 | 62.3 | 59.7 | 61.4 | 60.5 | 63.1 | 62.2 | 63.0 |
| Levalbuterol 0.63 mg | 62.5 | 61.4 | 60.8 | 63.4 | 61.7 | 63.1 | 62.8 | 63.4 | 63.5 | 63.1 | 63.8 | 60.7 | 63.2 | 62.0 | 62.9 | 62.6 | 62.3 |
Mean diastolic blood pressure measured at various timepoints minus the predose diastolic blood pressure (NCT00583947)
Timeframe: predose, various timeframes up to 5 hours post last dose
| Intervention | mmHg (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 15 min post dose 1 (n=51,52,40) | 30 min post dose 1 (n=51,52,40) | 60 min post dose 1 (n=51,51,40) | 15 min post dose 2 (n=50,51,40) | 30 min post dose 2 (n=47,50,40) | 60 min post dose 2 (n=46,50,37) | 30 min post last dose (n=49,52,40) | 60 min post last dose (n=49,52,40) | 1.5 hours post last dose (n=48,52,40) | 2 hours post last dose (n=50,52,40) | 2.5 hours post last dose (n=49,52,40) | 3 hours post last dose (n=50,52,40) | 3.5 hours post last dose (n=50,52,40) | 4 hours post last dose (n=50,52,40) | 4.5 hours post last dose (n=50,52,40) | 5 hours post last dose (n=50,52,40) | |
| Arformoterol 15 Mcg | -1.0 | -1.9 | -1.3 | -2.8 | -1.9 | -1.8 | -1.9 | -1.1 | -1.1 | -1.5 | -1.3 | -1.1 | -1.0 | -3.7 | -1.7 | -3.6 |
| Arformoterol 7.5 Mcg | -1.1 | -0.6 | -0.7 | 0.1 | -1.1 | -1.3 | -1.2 | -1.1 | -0.9 | -0.9 | -3.5 | -1.8 | -2.6 | -0.0 | -1.0 | -0.1 |
| Levalbuterol 0.63 mg | -1.1 | -1.7 | 0.8 | -1.1 | 0.8 | 0.0 | 0.8 | 0.8 | 0.1 | 1.4 | -1.9 | 0.8 | -0.4 | 0.5 | 0.2 | -0.1 |
PEFR is the fastest rate at which air can move through the airways during a forced expiration starting with fully inflated lungs as measured by peak flow meters. Change in PEFR was calculated as postdose value minus the predose value at each visit. (NCT00583947)
Timeframe: predose, various postdose times
| Intervention | liters/second (Mean) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 10 minutes post dose 1 (n=37,38,27) | 25 minutes post dose 1 (n=37,37,27) | 10 minutes post dose 2 (n=36,38,27) | 25 minutes post dose 2 (n=36,38,27) | 10 minutes post dose 3 (n=34,38,27) | 25 minutes post dose 3 (n=35,38,26) | 2 hours post dose 1 (n=36,37,27) | 4 hours post dose 1 (n=36,38,27) | 6 hours post dose 1 (n=36,38,27) | |
| Arformoterol 15 Mcg | 0.259 | 0.279 | 0.360 | 0.424 | 0.513 | 0.449 | 0.501 | 0.474 | 0.451 |
| Arformoterol 7.5 Mcg | 0.242 | 0.320 | 0.344 | 0.419 | 0.457 | 0.462 | 0.596 | 0.484 | 0.513 |
| Levalbuterol 0.63 mg | 0.322 | 0.399 | 0.458 | 0.452 | 0.524 | 0.539 | 0.575 | 0.509 | 0.324 |
Change in mean serum glucose at the specified timepoint minus the predose value. (NCT00583947)
Timeframe: predose, 2 and 6 hours post dose
| Intervention | mg/dl (Mean) | |
|---|---|---|
| 2 hours post dose 1 (n=48,47,39) | 6 hours post dose 1 (n=49,48,38) | |
| Arformoterol 15 Mcg | 32.9 | 18.6 |
| Arformoterol 7.5 Mcg | 22.4 | 12.1 |
| Levalbuterol 0.63 mg | 27.1 | 20.3 |
Heart rate measured at various timepoints minus the heart rate at predose. (NCT00583947)
Timeframe: predose, various timeframes up to 5 hours post last dose
| Intervention | beats per minute (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 15 min post dose 1 (n=51,52,40) | 30 min post dose 1 (n=51,52,40) | 60 min post dose 1 (n=51,51,40) | 15 min post dose 2 (n=50,51,40) | 30 min post dose 2 (n=47,50,40) | 60 min post dose 2 (n=46,50,37) | 30 min post last dose (n=49,52,40) | 60 min post last dose (n=49,52,40) | 1.5 hours post last dose (n=48,52,40) | 2 hours post last dose (n=50,52,40) | 2.5 hours post last dose (n=49,52,40) | 3 hours post last dose (n=50,52,40) | 3.5 hours post last dose (n=50,52,40) | 4 hours post last dose (n=50,52,40) | 4.5 hours post last dose (n=50,52,40) | 5 hours post last dose (n=50,51,40) | |
| Arformoterol 15 Mcg | 2.3 | 2.5 | 6.5 | 5.5 | 6.3 | 9.5 | 9.0 | 10.0 | 8.3 | 8.9 | 7.8 | 6.4 | 7.9 | 7.4 | 6.9 | 5.8 |
| Arformoterol 7.5 Mcg | 0.5 | 2.0 | 4.4 | 2.8 | 4.5 | 4.7 | 5.6 | 8.6 | 7.1 | 6.6 | 5.5 | 5.9 | 5.1 | 4.6 | 4.9 | 5.3 |
| Levalbuterol 0.63 mg | 1.6 | 3.2 | 8.7 | 7.8 | 10.0 | 13.2 | 11.9 | 8.7 | 8.9 | 5.6 | 6.8 | 6.7 | 5.9 | 6.6 | 5.9 | 5.0 |
Change in mean serum potassium at the specified timepoint minus the predose value. (NCT00583947)
Timeframe: predose, 2 and 6 hours post dose
| Intervention | mEq/L (Mean) | |
|---|---|---|
| 2 hours post dose 1 (n=48,47,38) | 6 hours post dose 1 (n=48,49,38) | |
| Arformoterol 15 Mcg | -0.62 | -0.39 |
| Arformoterol 7.5 Mcg | -0.42 | -0.31 |
| Levalbuterol 0.63 mg | -0.58 | -0.23 |
If the mean plasma concentration was 'below the limit of quantification' (BLQ) which was set as <=0.5 picograms/milliliter, the value is displayed as a zero. (NCT00583947)
Timeframe: predose, various postdose times
| Intervention | picogram/milliliter (Mean) | ||||
|---|---|---|---|---|---|
| predose (n=51,52,39) | 25 minutes post dose 1 (n=50,46,36) | 25 minutes post dose 2 (n=48,47,36) | 2 hours post dose 1 (n=50,51,38) | 6 hours post dose 1 (n=50,50,37) | |
| Arformoterol 15 Mcg | 0.737 | 1.659 | 3.325 | 4.189 | 2.818 |
| Arformoterol 7.5 Mcg | 0 | 2.236 | 1.845 | 1.885 | 0.874 |
| Levalbuterol 0.63 mg | 0.646 | 2.402 | 0 | 0 | 0 |
Mean systolic blood pressure measured at various timepoints minus the mean systolic blood pressure at predose (NCT00583947)
Timeframe: predose, various timeframes up to 5 hours post last dose
| Intervention | mmHg (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 15 min post dose 1 (n=51,52,40) | 30 min post dose 1 (n=51,52,40) | 60 min post dose 1 (n=51,51,40) | 15 min post dose 2 (n=50,51,40) | 30 min post dose 2 (n=47,50,40) | 60 min post dose 2 (n=46,50,37) | 30 min post last dose (n=49,52,40) | 60 min post last dose (n=49,52,40) | 1.5 hours post last dose (n=48,52,40) | 2 hours post last dose (n=50,52,40) | 2.5 hours post last dose (n=49,52,40) | 3 hours post last dose (n=50,52,40) | 3.5 hours post last dose (n=50,52,40) | 4 hours post last dose (n=50,52,40) | 4.5 hours post last dose (n=50,52,40) | 5 hours post last dose (n=50,52,40) | |
| Arformoterol 15 Mcg | 2.0 | -0.3 | 2.6 | 1.6 | 1.4 | 1.8 | 1.1 | 4.4 | 2.4 | 1.3 | 0.7 | 1.3 | 0.9 | -0.0 | 0.9 | 1.6 |
| Arformoterol 7.5 Mcg | -0.4 | 0.9 | 1.1 | -0.3 | 0.8 | -0.3 | -0.4 | 1.5 | 0.3 | 1.8 | -0.0 | 0.6 | 1.7 | 0.6 | 1.7 | 2.5 |
| Levalbuterol 0.63 mg | 0.8 | 2.6 | 3.7 | 2.6 | 3.3 | 4.0 | 2.4 | 3.5 | 1.8 | 2.3 | 0.4 | 3.9 | 1.2 | 1.3 | 2.2 | 4.5 |
Forced Expiratory Volume in one second (FEV1) is the volume of air forcibly exhaled in one second as measured by a spirometer. (NCT00583947)
Timeframe: predose, various postdose times
| Intervention | liters (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| predose (n=37,38,27) | 10 minutes post dose 1 (n=37,38,27) | 25 minutes post dose 1 (n=37,37,27) | 10 minutes post dose 2 (n=36,38,27) | 25 minutes post dose 2 (n=36,38,27) | 10 minutes post dose 3 (n=34,38,27) | 25 minutes post dose 3 (n=35,38,26) | 2 hours post dose 1 (n=36,37,27) | 4 hours post dose 1 (n=36,38,27) | 6 hours post dose 1 (n=36,38,27) | |
| Arformoterol 15 Mcg | 1.486 | 1.620 | 1.644 | 1.661 | 1.669 | 1.689 | 1.700 | 1.704 | 1.684 | 1.660 |
| Arformoterol 7.5 Mcg | 1.552 | 1.668 | 1.695 | 1.721 | 1.714 | 1.731 | 1.740 | 1.754 | 1.722 | 1.725 |
| Levalbuterol 0.63 mg | 1.554 | 1.714 | 1.712 | 1.741 | 1.735 | 1.775 | 1.782 | 1.784 | 1.732 | 1.667 |
Heart rate measured at various timepoints: predose and timepoints after each of the three dosings. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes). (NCT00583947)
Timeframe: predose, various timeframes up to 5 hours post last dose
| Intervention | beats per minute (Mean) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Predose (n=51,52,40) | 15 min post dose 1 (n=51,52,40) | 30 min post dose 1 (n=51,52,40) | 60 min post dose 1 (n=51,51,40) | 15 min post dose 2 (n=50,51,40) | 30 min post dose 2 (n=47,50,40) | 60 min post dose 2 (n=46,50,37) | 30 min post last dose (n=49,52,40) | 60 min post last dose (n=49,52,40) | 1.5 hours post last dose (n=48,52,40) | 2 hours post last dose (n=50,52,40) | 2.5 hours post last dose (n=49,52,40) | 3 hours post last dose (n=50,52,40) | 3.5 hours post last dose (n=50,52,40) | 4 hours post last dose (n=50,52,40) | 4.5 hours post last dose (n=50,52,40) | 5 hours post last dose (n=50,51,40) | |
| Arformoterol 15 Mcg | 87.0 | 89.4 | 89.5 | 93.5 | 92.5 | 93.3 | 96.1 | 96.1 | 97.1 | 95.3 | 95.9 | 94.8 | 93.4 | 95.0 | 94.5 | 93.9 | 92.9 |
| Arformoterol 7.5 Mcg | 84.7 | 85.2 | 86.6 | 89.0 | 87.5 | 88.9 | 89.3 | 90.3 | 93.3 | 91.8 | 91.2 | 90.2 | 90.6 | 89.8 | 89.3 | 89.6 | 89.8 |
| Levalbuterol 0.63 mg | 87.6 | 89.3 | 90.9 | 96.4 | 95.4 | 97.1 | 100.4 | 99.2 | 96.0 | 96.2 | 93.0 | 94.1 | 94.1 | 93.3 | 94.0 | 93.3 | 92.4 |
PEFR is the fastest rate at which air can move through the airways during a forced expiration starting with fully inflated lungs as measured by peak flow meters. (NCT00583947)
Timeframe: predose, various postdose times
| Intervention | liters/second (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| predose (n=37,38,27) | 10 minutes post dose 1 (n=37,38,27) | 25 minutes post dose 1 (n=37,37,27) | 10 minutes post dose 2 (n=36,38,27) | 25 minutes post dose 2 (n=36,38,27) | 10 minutes post dose 3 (n=34,38,27) | 25 minutes post dose 3 (n=35,38,26) | 2 hours post dose 1 (n=36,37,27) | 4 hours post dose 1 (n=36,38,27) | 6 hours post dose 1 (n=36,38,27) | |
| Arformoterol 15 Mcg | 3.565 | 3.824 | 3.844 | 3.925 | 3.989 | 4.077 | 4.017 | 4.066 | 4.039 | 4.016 |
| Arformoterol 7.5 Mcg | 3.546 | 3.788 | 3.877 | 3.890 | 3.964 | 4.003 | 4.007 | 4.178 | 4.029 | 4.058 |
| Levalbuterol 0.63 mg | 3.604 | 3.926 | 4.003 | 4.053 | 4.047 | 4.156 | 4.176 | 4.221 | 4.155 | 3.970 |
(NCT00583947)
Timeframe: Predose, 2 and 6 hours post dose 1
| Intervention | mg/dl (Mean) | ||
|---|---|---|---|
| Predose (n=51,52,40) | 2 hours post dose 1 (n=48,47,39) | 6 hours post dose 1 (n=49,48,38) | |
| Arformoterol 15 Mcg | 87.6 | 120.6 | 106.3 |
| Arformoterol 7.5 Mcg | 87.5 | 108.6 | 99.0 |
| Levalbuterol 0.63 mg | 86.4 | 114.5 | 107.6 |
(NCT00583947)
Timeframe: Predose, 2 hours and 6 hours postdose 1
| Intervention | mEq/L (Mean) | ||
|---|---|---|---|
| Predose (n=51,52,39) | 2 hours post dose 1 (n=48,47,38) | 6 hours post dose 1 (n=48,49,38) | |
| Arformoterol 15 Mcg | 4.31 | 3.71 | 3.87 |
| Arformoterol 7.5 Mcg | 4.27 | 3.83 | 3.95 |
| Levalbuterol 0.63 mg | 4.25 | 3.67 | 3.99 |
Systolic blood pressure measured at various timepoints: predose and timepoints after each of the three dosings. Each treatment consists of one nebulization every 30 minutes over a 60 minute treatment interval (totaling 3 cumulative dosings at 0,30 and 60 minutes). (NCT00583947)
Timeframe: predose, various timeframes up to 5 hours post last dose
| Intervention | mmHg (Mean) | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Predose (n=51,52,40) | 15 min post dose 1 (n=51,52,40) | 30 min post dose 1 (n=51,52,40) | 60 min post dose 1 (n=51,51,40) | 15 min post dose 2 (n=50,51,40) | 30 min post dose 2 (n=47,50,40) | 60 min post dose 2 (n=46,50,37) | 30 min post last dose (n=49,52,40) | 60 min post last dose (n=49,52,40) | 1.5 hours post last dose (n=48,52,40) | 2 hours post last dose (n=50,52,40) | 2.5 hours post last dose (n=49,52,40) | 3 hours post last dose (n=50,52,40) | 3.5 hours post last dose (n=50,52,40) | 4 hours post last dose (n=50,52,40) | 4.5 hours post last dose (n=50,52,40) | 5 hours post last dose (n=50,52,40) | |
| Arformoterol 15 Mcg | 100.6 | 102.6 | 100.3 | 103.2 | 102.1 | 101.9 | 102.9 | 101.6 | 104.9 | 103.0 | 101.8 | 101.3 | 101.9 | 101.4 | 100.5 | 101.5 | 102.1 |
| Arformoterol 7.5 Mcg | 101.5 | 101.2 | 102.5 | 102.7 | 101.7 | 102.8 | 101.9 | 101.2 | 103.0 | 101.9 | 103.4 | 101.5 | 102.1 | 103.2 | 102.1 | 103.2 | 104.1 |
| Levalbuterol 0.63 mg | 102.1 | 102.9 | 104.6 | 105.8 | 105.0 | 106.4 | 107.2 | 105.0 | 106.1 | 104.8 | 104.6 | 103.0 | 106.1 | 103.4 | 103.6 | 104.5 | 106.7 |
"Quartile discrepancies refer to the difference between~the participant-recorded number of actuations and the participant-recorded~counter readout at each of the 4 weekly visit intervals [ie, quartiles] to~evaluate whether there was any difference in agreement over the life of~the inhaler. The Quartile Discrepancy Rate was calculated as 100 multiplied by the total number of discrepancies per Quartile across all participant who used at least 90% of the labeled actuations divided by the total number of actuations per Quartile in the same population." (NCT00604500)
Timeframe: 4-week Treatment Period
| Intervention | discrepancies per 100 actuations (Number) |
|---|---|
| MF/F MDI 100/10 mcg BID (With Dose Counter) | 0.13 |
Discrepancy Size refers to the magnitude of the discrepancy between the dose counter readout and the number of recorded actuations (definition of discrepancy). Overall Discrepancy Size was calculated as 100 multiplied by the sum of the absolute values from each Dose Counter Discrepancy Size across all participants who used at least 90% of the labeled actuations divided by the total number of recorded actuations in the same participant population. (NCT00604500)
Timeframe: 4-week Treatment Period
| Intervention | Discrepancy Size Per 100 actuations (Number) |
|---|---|
| MF/F MDI 100/10 mcg BID (With Dose Counter) | 0.14 |
Overall discrepancies refer to the difference between the participant-recorded number of actuations and the participant-recorded dose counter readout across the 4-week Treatment Period. The Overall Discrepancy Rate was calculated as 100 multiplied by the total number of discrepancies across all participants who used at least 90% of the labeled actuations divided by the total number of actuations in the same participant population (Completer Population). (NCT00604500)
Timeframe: 4-week Treatment Period
| Intervention | Overall discrepancies per 100 actuations (Number) |
|---|---|
| MF/F MDI 100/10 mcg BID (With Dose Counter) | 0.13 |
The difference in the final MDI dose counter readout and the total number of recorded actuations at the end-of-use. Dose Counter end-of-use agreement was calculated as the sum of the absolute difference between the final dose counter readout and the number of recorded actuations across all participants who used at least 90% of the labeled actuations (excluding participants who used the inhaler beyond the labeled number of actuations) divided by the total number of participants in this population. No participant used more than two inhalers during the treatment period. (NCT00604500)
Timeframe: 4-week Treatment Period
| Intervention | Number of inhalers (Number) |
|---|---|
| MF/F MDI 100/10 mcg BID (With Dose Counter) | 175 |
(NCT00626522)
Timeframe: Baseline and treatment Week 4
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 200 μg / Formoterol 6 μg | 0.294 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.357 |
| Aclidinium 200 μg / Formoterol 18 μg | 0.349 |
| Aclidinium 200 μg | 0.184 |
| Formoterol 12 μg | 0.216 |
| Placebo | 0.044 |
(NCT00626522)
Timeframe: Baseline and treatment Week 4
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 200 μg / Formoterol 6 μg | 0.197 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.256 |
| Aclidinium 200 μg / Formoterol 18 μg | 0.250 |
| Aclidinium 200 μg | 0.088 |
| Formoterol 12 μg | 0.134 |
| Placebo | -0.033 |
(NCT00626522)
Timeframe: Baseline and treatment Week 4
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 200 μg / Formoterol 6 μg | 0.042 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.085 |
| Aclidinium 200 μg / Formoterol 18 μg | 0.044 |
| Aclidinium 200 μg | -0.017 |
| Formoterol 12 μg | 0.014 |
| Placebo | -0.031 |
(NCT00626522)
Timeframe: Baseline and treatment Week 4
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 200 μg / Formoterol 6 μg | 0.206 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.266 |
| Aclidinium 200 μg / Formoterol 18 μg | 0.272 |
| Aclidinium 200 μg | 0.094 |
| Formoterol 12 μg | 0.137 |
| Placebo | -0.033 |
(NCT00626522)
Timeframe: Baseline and treatment Week 4
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 200 μg / Formoterol 6 μg | 0.170 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.219 |
| Aclidinium 200 μg / Formoterol 18 μg | 0.230 |
| Aclidinium 200 μg | 0.075 |
| Formoterol 12 μg | 0.099 |
| Placebo | -0.036 |
Total number of severe asthma exacerbations per treatment group (NCT00628758)
Timeframe: 26 weeks
| Intervention | Severe Exacerbations (Number) |
|---|---|
| Symbicort | 10 |
| Conventional BP | 10 |
Quality-of-Life assessment; grouped in four domains;activity limitation, symptoms, emotional function and exposure to environmental stimuli, using with a scale from 1 to 7 where 1 represents the greatest possible impairment and 7 represents the least impairment. (NCT00628758)
Timeframe: Baseline and 26 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort | 3.98 |
| Conventional BP | 3.97 |
Mean use of as-needed medication per day during treatment period (NCT00628758)
Timeframe: Daily recording during the treatment period of 26 weeks
| Intervention | inhalations per day (Mean) |
|---|---|
| Symbicort | 0.91 |
| Conventional BP | 0.68 |
Time to severe exacerbation among patients (NCT00628758)
Timeframe: 26 weeks
| Intervention | days (Mean) |
|---|---|
| Symbicort | 120.3 |
| Conventional Best Practice (BP) | 103.7 |
Lung function (FEV1) was measured 5 minutes after the first dose of study drug. The results are expressed as a percentage in relation to the baseline value (NCT00628862)
Timeframe: baseline and 5 minutes anter first dose
| Intervention | percent of baseline (Geometric Mean) |
|---|---|
| Formoterol 4.5 Bid | 110.16 |
| Formoterol 9.0 Bid | 110.24 |
| Placebo | 101.25 |
Lung function (FEV1) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value (NCT00628862)
Timeframe: baseline at week 0 and pre-dose at weeks 4, 8 and 12
| Intervention | percent of baseline (Geometric Mean) |
|---|---|
| Formoterol 4.5 Bid | 104.54 |
| Formoterol 9.0 Bid | 104.65 |
| Placebo | 99.77 |
FEV1 (expressed as litres [L]) is a spirometric measure of lung function. FEV1 was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value. (NCT00628862)
Timeframe: from baseline up to 12 weeks
| Intervention | percent of baseline (Geometric Mean) |
|---|---|
| Formoterol 4.5 Bid | 112.9 |
| Formoterol 9.0 Bid | 113.36 |
| Placebo | 101.28 |
Forced Vital Capacity (FVC) is a spirometric measure of lung function. FVC was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value (NCT00628862)
Timeframe: from baseline up to 12 weeks
| Intervention | percent of baseline (Geometric Mean) |
|---|---|
| Formoterol 4.5 Bid | 109.73 |
| Formoterol 9.0 Bid | 109.92 |
| Placebo | 102.11 |
Patients were asked to measure and record lung function (peak expiratory flow [PEF] measured in the evening). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value (NCT00628862)
Timeframe: run-in period and 12 week
| Intervention | L/min (Mean) |
|---|---|
| Formoterol 4.5 Bid | 13.15 |
| Formoterol 9.0 Bid | 15.76 |
| Placebo | 2.36 |
Patients were asked to record the night-time awakenings due to symptoms (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value (NCT00628862)
Timeframe: run-in period up to 12 weeks
| Intervention | scores on a scale per day (Mean) |
|---|---|
| Formoterol 4.5 Bid | -0.1318 |
| Formoterol 9.0 Bid | -0.1748 |
| Placebo | -0.0466 |
Patients were asked to record breathlessness (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value (NCT00628862)
Timeframe: run-in period up to 12 weeks
| Intervention | scores on a scale per day (Mean) |
|---|---|
| Formoterol 4.5 Bid | -0.4068 |
| Formoterol 9.0 Bid | -0.4531 |
| Placebo | -0.2626 |
Patients were asked to measure and record lung function (peak expiratory flow [PEF] measured in the morning). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value (NCT00628862)
Timeframe: run-in period and 12 week
| Intervention | L/min (Mean) |
|---|---|
| Formoterol 4.5 Bid | 16.27 |
| Formoterol 9.0 Bid | 18.34 |
| Placebo | 3.60 |
Lung function (FVC) was measured 5 minutes after the first dose of study drug, The results are expressed as a percentage in relation to the baseline value (NCT00628862)
Timeframe: baseline and 5 minutes anter first dose
| Intervention | percent of baseline (Geometric Mean) |
|---|---|
| Formoterol 4.5 Bid | 108.50 |
| Formoterol 9.0 Bid | 108.88 |
| Placebo | 101.59 |
Lung function (FVC) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value (NCT00628862)
Timeframe: baseline at week 0 and pre-dose at weeks 4, 8 and 12
| Intervention | percent of baseline (Geometric Mean) |
|---|---|
| Formoterol 4.5 Bid | 103.62 |
| Formoterol 9.0 Bid | 103.36 |
| Placebo | 100.73 |
Patients were asked to complete the St George's Respiratory Questionnaire (SGRQ). Subscale symptom score ranges from 0 to 100% and measures the effect of respiratory symptoms, frequency, and severity on quality of life. A score of 0 indicates the best possible status. Results are expressed as the change from baseline score with a decrease in score indicating improvement. (NCT00628862)
Timeframe: 12 weeks (end of run-in to last visit)
| Intervention | Scores on a scale (Mean) |
|---|---|
| Formoterol 4.5 Bid | -5.46 |
| Formoterol 9.0 Bid | -6.38 |
| Placebo | -2.02 |
Patients were asked to record reliever medication use. Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value (NCT00628862)
Timeframe: 12 weeks (end of run-in to last visit)
| Intervention | medication doses per day (Mean) |
|---|---|
| Formoterol 4.5 Bid | -0.60 |
| Formoterol 9.0 Bid | -0.97 |
| Placebo | -0.23 |
Patients were asked to record cough (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value (NCT00628862)
Timeframe: run-in period up to 12 weeks
| Intervention | scores on a scale per day (Mean) |
|---|---|
| Formoterol 4.5 Bid | -0.3250 |
| Formoterol 9.0 Bid | -0.4088 |
| Placebo | -0.2016 |
"The treatment efficacy was rated by subjects at the end of the evaluation period in autumn 2008. Subjects rated their asthma symptoms in comparison to previous autumn using the categories: much worse, worse, the same, better, or much better.~The categories much better or better were grouped as improved. The categories the same, worse or much worse were grouped as not improved." (NCT00633919)
Timeframe: 8 weeks
| Intervention | Participants (Number) | ||
|---|---|---|---|
| Subject evaluation: Improved | Subject evaluation: Not improved | Subject evaluation: Missing data | |
| Active | 28 | 8 | 1 |
| Placebo | 28 | 13 | 0 |
"The treatment efficacy was rated by both subject and investigator at the end of the evaluation period in autumn 2007. Subjects rated their asthma symptoms in comparison to previous autumns and investigators rated the asthma symptoms in comparison to when subjects entered the trial, using the categories: much worse, worse, the same, better, or much better.~The categories much better or better were grouped as improved. The categories the same, worse or much worse were grouped as not improved." (NCT00633919)
Timeframe: 8 weeks
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Subject evalution: Improved | Subject evaluation: Not improved | Investigator evaluation: Improved | Investigator evaluation: Not improved | |
| Active | 30 | 17 | 33 | 14 |
| Placebo | 33 | 14 | 30 | 17 |
"The treatment efficacy was rated by investigators at the end of the evaluation period in autumn 2008. Investigators rated the asthma symptoms in comparison to when subjects entered the trial, using the categories: much worse, worse, the same, better, or much better.~The categories much better or better were grouped as improved. The categories the same, worse or much worse were grouped as not improved." (NCT00633919)
Timeframe: 8 weeks
| Intervention | Participants (Number) | ||
|---|---|---|---|
| Investigator evaluation: Improved | Investigator evaluation: Not improved | Investigator evaluation: Missing data | |
| Active | 30 | 7 | 0 |
| Placebo | 24 | 17 | 0 |
"Scoring per inhalation/tablet: 1-2 inhalations twice daily of salbutamol (200 ug per inhalation), 2 scores; 1-2 inhalation twice daily of budesonide/formoterol 80 (4.5 ug per inhalation), 4 scores; 1 inhalation twice daily of budesonide/formoterol 160 (4.5 ug per inhalation), 8 scores; up to 10 tablets once daily of prednisone (5 mg), 1.6 scores. The total maximum daily scores were 40.~The daily score for each medication step was calculated by multiplying the score per inhalation/tablet with the number of inhalations/tablets used (entered as units in the daily diary by the subject)." (NCT00633919)
Timeframe: 8 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Active | 4.4 |
| Placebo | 4.7 |
"Scoring per inhalation/tablet: 1-2 inhalations twice daily of salbutamol (200 ug per inhalation), 2 scores; 1-2 inhalation twice daily of budesonide/formoterol 80 (4.5 ug per inhalation), 4 scores; 1 inhalation twice daily of budesonide/formoterol 160 (4.5 ug per inhalation), 8 scores; up to 10 tablets once daily of prednisone (5 mg), 1.6 scores. The total maximum daily scores were 40.~The daily score for each medication step was calculated by multiplying the score per inhalation/tablet with the number of inhalations/tablets used (entered as units in the daily diary by the subject)." (NCT00633919)
Timeframe: 8 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Active | 4.1 |
| Placebo | 3.6 |
(NCT00635882)
Timeframe: Baseline and Days 2-15
| Intervention | liters/minute (Mean) | |
|---|---|---|
| Baseline | Mean Change from Baseline to Days 2-15 | |
| MF DPI 200 mcg | 466.3 | 30.3 |
| MF MDI 200 mcg | 473.3 | 30.8 |
| MF/F MDI 100/10 mcg | 452.6 | 48.1 |
| MF/F MDI 200/10 mcg | 421.2 | 46.9 |
| MF/F MDI 400/10 mcg | 468.7 | 69.8 |
| Placebo | 413.2 | -9.0 |
Mannitol challenge (also referred to as PD15) is the provocative dose of mannitol required to produce a 15% reduction in the forced expiratory volume (in liters) in one second (FEV1). (NCT00635882)
Timeframe: Baseline to Day 15
| Intervention | milligrams (Mean) | |
|---|---|---|
| Baseline | Mean Change from Baseline to Day 15 | |
| MF DPI 200 mcg | 137.6 | 159.4 |
| MF MDI 200 mcg | 126.0 | 146.2 |
| MF/F MDI 100/10 mcg | 102.2 | 176.6 |
| MF/F MDI 200/10 mcg | 48.6 | 153.8 |
| MF/F MDI 400/10 mcg | 67.9 | 162.9 |
| Placebo | 159.4 | -63.7 |
Twice daily, participants rated the following asthma symptoms as experienced during the time period since the last evaluation: wheezing, difficulty breathing, and cough on a scale of 0 (none) to 3 (severe, very uncomfortable and interfered with most or all of normal daily activities/sleep). The total asthma symptom score ranged from 0 to 9. The results were recorded in the participant's diary. (NCT00635882)
Timeframe: Baseline and Days 2-15
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Mean Change from Baseline to Days 2-15 | |
| MF DPI 200 mcg | 1.5 | -1.2 |
| MF MDI 200 mcg | 1.1 | -0.5 |
| MF/F MDI 100/10 mcg | 1.6 | -0.7 |
| MF/F MDI 200/10 mcg | 1.2 | -0.7 |
| MF/F MDI 400/10 mcg | 2.2 | -1.5 |
| Placebo | 1.4 | -0.2 |
(NCT00635882)
Timeframe: Baseline to Day 14
| Intervention | percentage of eNO (Mean) |
|---|---|
| MF/F MDI 100/10 mcg | -35.3 |
| MF/F MDI 200/10 mcg | -45.4 |
| MF/F MDI 400/10 mcg | -61.4 |
| MF DPI 200 mcg | -51.3 |
| MF MDI 200 mcg | -46.1 |
| Placebo | 0.1 |
(NCT00635882)
Timeframe: Baseline and Days 1-15
| Intervention | liters/minute (Mean) | |
|---|---|---|
| Baseline | Mean Change from Baseline to Days 1-15 | |
| MF DPI 200 mcg | 484.4 | 20.2 |
| MF MDI 200 mcg | 472.5 | 28.3 |
| MF/F MDI 100/10 mcg | 462.0 | 47.7 |
| MF/F MDI 200/10 mcg | 437.2 | 34.5 |
| MF/F MDI 400/10 mcg | 486.7 | 66.8 |
| Placebo | 422.7 | 4.5 |
Twice daily, participants rated the following asthma symptoms as experienced during the time period since the last evaluation: wheezing, difficulty breathing, and cough on a scale of 0 (none) to 3 (severe, very uncomfortable and interfered with most or all of normal daily activities/sleep). The total asthma symptom score ranged from 0 to 9. The results were recorded in the participant's diary. (NCT00635882)
Timeframe: Baseline and Days 1-15
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Baseline | Mean Change from Baseline to Days 1-15 | |
| MF DPI 200 mcg | 1.6 | -1.1 |
| MF MDI 200 mcg | 1.6 | -0.7 |
| MF/F MDI 100/10 mcg | 1.7 | -0.4 |
| MF/F MDI 200/10 mcg | 1.1 | -0.6 |
| MF/F MDI 400/10 mcg | 2.1 | -1.4 |
| Placebo | 1.7 | -0.3 |
(NCT00635882)
Timeframe: Baseline to Day 7
| Intervention | percentage of eNO (Mean) |
|---|---|
| MF/F MDI 100/10 mcg | -37.9 |
| MF/F MDI 200/10 mcg | -39.7 |
| MF/F MDI 400/10 mcg | -45.6 |
| MF DPI 200 mcg | -46.0 |
| MF MDI 200 mcg | -37.2 |
| Placebo | 4.8 |
(NCT00635882)
Timeframe: Baseline to Day 14
| Intervention | percentage of Sputum Eosinophil Count (Mean) |
|---|---|
| MF/F MDI 100/10 mcg | 21.1 |
| MF/F MDI 200/10 mcg | -35.5 |
| MF/F MDI 400/10 mcg | -75.4 |
| MF DPI 200 mcg | -55.3 |
| MF MDI 200 mcg | -33.7 |
| Placebo | 71.7 |
(NCT00635882)
Timeframe: Baseline
| Intervention | ppb (Mean) |
|---|---|
| MF/F MDI 100/10 mcg | 54.8 |
| MF/F MDI 200/10 mcg | 70.0 |
| MF/F MDI 400/10 mcg | 77.1 |
| MF DPI 200 mcg | 102.6 |
| MF MDI 200 mcg | 66.2 |
| Placebo | 79.6 |
The forced expiratory volume in the first second, expressed as a percent predicted. (NCT00643578)
Timeframe: 1 hour after dose
| Intervention | percent predicted (Mean) |
|---|---|
| 12 Mcg of Formoterol | 88 |
| 24 Mcg of Formoterol | 91 |
The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second. (NCT00643578)
Timeframe: 3-7 days after visits 1 and 2
| Intervention | mg/mL (Geometric Mean) |
|---|---|
| 12 Mcg Formoterol | 7 |
| 24 Mcg Formoterol | 16 |
TDI is a multidimensional clinical instrument developed to provide a comprehensive assessment of change in dyspnea after an intervention, considering three components (functional impairment, magnitude of task, and magnitude of effort). It ranges from -9 (major deterioration) to +9 (major improvement). (NCT00680056)
Timeframe: After 2 week of each treatment
| Intervention | score on scale (Mean) |
|---|---|
| Formoterol Plus Placebo (Tiotropium) Treatment | 2.9 |
| Formoterol Plus Tiotropium Treatment | 3.8 |
Percentage change from baseline in time to the limit of tolerance on a high intensity constant-speed treadmill exercise test (with a speed corresponding to 80% of that obtained during incremental test) (NCT00680056)
Timeframe: Baseline and after 2 weeks with each treatment
| Intervention | Percentage change (Mean) |
|---|---|
| Formoterol Plus Placebo (Tiotropium) Treatment | 68 |
| Formoterol Plus Tiotropium Treatment | 124 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at last week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work. (NCT00702325)
Timeframe: 12 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 99 | 81 |
| Symbicort | 112 | 100 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at last week of treatment - During the past week, you could feel your medication begin to work right away (NCT00702325)
Timeframe: 12 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 112 | 95 |
| Symbicort | 123 | 109 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.14 |
| Budesonide | 0.07 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 5 at first week of treatment - During the past week, you were satisfied with how quickly you felt your study medication began to work. (NCT00702325)
Timeframe: 1 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 83 | 70 |
| Symbicort | 96 | 86 |
Diary assessment of participants age 12 years and older and 18 years and older who agreed with OEQ Item 2 at first week of treatment - During the past week, you could feel your medication begin to work right away (NCT00702325)
Timeframe: 1 week
| Intervention | Participants (Number) | |
|---|---|---|
| 12 years and older | 18 years and older | |
| Budesonide | 95 | 81 |
| Symbicort | 113 | 101 |
There are 5 questions in the survey, and each question has 5 responses (total score for each question can range from 1 to 5). To score the survey, responses to the 5 questions are added to yield a total score that ranges from 5 (poor control of asthma control) to 25 (complete control of asthma). Score of 20 or higher was indicative of well-controlled asthma. (NCT00702325)
Timeframe: 12 weeks
| Intervention | Proportion of Participants (Number) |
|---|---|
| Symbicort | 0.524 |
| Budesonide | 0.518 |
Total number of participants who withdrew due to a predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma meds) (NCT00702325)
Timeframe: 12 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 18 |
| Budesonide | 28 |
Total number of participants with any first predefined asthma event (decrease in FEV1 ≥ 20%,or to <40% of predicted normal value,12 puffs of albuterol pMDI per day on 3 or more days, decrease in morning PEF ≥ 20% on 3 or more days, use of rescue medication for 2 or more nights, emergency treatment, hospitalization, use of other asthma medication) (NCT00702325)
Timeframe: 12 weeks
| Intervention | Participants (Number) |
|---|---|
| Symbicort | 57 |
| Budesonide | 67 |
Diary assessment of total daily puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Puffs/day (Mean) |
|---|---|
| Symbicort | -1.27 |
| Budesonide | -0.62 |
Mean change of the FEF (25-75%) value at the baseline (Visit 3) compared to average value of the FEF (25-75%) recorded at visits during treatment period (to week 12). The mean change was calculated. (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/second (Mean) |
|---|---|
| Symbicort | 0.21 |
| Budesonide | 0.12 |
Diary assessment of total (percent) days free from rescue medication use for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| Symbicort | 29.31 |
| Budesonide | 17.70 |
Diary assessment of total daytime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Puffs/day (Mean) |
|---|---|
| Symbicort | -0.48 |
| Budesonide | -0.27 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort | 25.34 |
| Budesonide | 7.53 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters/minute (Mean) |
|---|---|
| Symbicort | 21.61 |
| Budesonide | 7.67 |
Diary assessment of daytime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS) (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.33 |
| Budesonide | -0.24 |
Diary assessment of number of nights free from awakenings due to asthma; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Number of nights (Mean) |
|---|---|
| Symbicort | 17.51 |
| Budesonide | 11.85 |
Diary assessment of number (percent) of asthma-control days (defined as days that were free of symptoms and nighttime and daytime rescue medication use); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| Symbicort | 21.89 |
| Budesonide | 15.12 |
There are 6 questions in the survey, and each question has 5 responses (total score for each question can range from 6 to 13). Responses to the 6 questions were added to yield a total score that ranged from 36 to 78. Scoring is based on a norm-based method. Higher AIS scores indicated more asthma impact and poorer quality of life; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period. (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -4.05 |
| Budesonide | -2.72 |
Diary assessment of nighttime asthma symptoms score (treatment average) by ICS dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period; full analysis set (FAS) (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.38 |
| Budesonide | -0.26 |
Mean change in overall score at end of treatment for participants age 17 years and older (scores ranged from 1 to 7, with higher scores indicating better quality of life); mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | 0.55 |
| Budesonide | 0.33 |
Diary assessment of total asthma symptoms score (treatment average) by Inhaled Corticosteroid (ICS) dose at entry. Asthma symptoms are cough, wheeze and shortness of breath. Each symptom is usually rated from 0-3: 0-no symptoms, 1-mild, 2-moderate and 3-severe. Change from baseline (Visit 3) mean value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Scores on a scale (Mean) |
|---|---|
| Symbicort | -0.35 |
| Budesonide | -0.23 |
Mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Liters (Mean) |
|---|---|
| Symbicort | 0.16 |
| Budesonide | 0.07 |
Diary assessment of number (percent) of days free from asthma symptoms by ICS dose at entry; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| Symbicort | 23.99 |
| Budesonide | 17.55 |
Diary assessment of total nighttime puffs of rescue medication used for asthma symptoms relief; mean change from baseline (Visit 3) value to average value recorded at visits during treatment period (NCT00702325)
Timeframe: Baseline to 12 weeks
| Intervention | Puffs/day (Mean) |
|---|---|
| Symbicort | -0.79 |
| Budesonide | -0.35 |
(NCT00706446)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|---|
| 1 - Tiotropium Plus ICS in the Arg/Arg Genotype | 3 |
| 2 - Tiotropium Plus ICS in the Arg/Gly Genotype | 15 |
| 3 - Tiotropium Plus ICS in the Gly/Gly Genotype | 6 |
| 4 - Salmeterol or Formoterol Plus ICS in the Arg/Arg Genotype | 6 |
| 5 - Salmeterol or Formoterol Plus ICS in the Arg/Gly Genotype | 12 |
| 6 - Salmeterol or Formoterol Plus ICS in the Gly/Gly Genotype | 9 |
Nocturnal Symptom Score Scale: 0 = None; 1 = Symptoms causing early awakening or awakening once during the night; 2 = Symptoms causing early awakening or awakening two or more times during the night; 3 = Symptoms causing awakening for most time during the night, 4 = Symptoms which were so severe that I could not sleep at all (NCT00706914)
Timeframe: Week 4 of treatment
| Intervention | Units on a scale (Mean) |
|---|---|
| Once-daily Aclidinium/Formoterol | -0.15 |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | -0.09 |
| Formoterol BID | -0.35 |
FEV1 values obtained at 30, 60, 120, and 180 minutes after the morning study drug dose (NCT00706914)
Timeframe: Week 4 of treatment
| Intervention | Liters (Mean) |
|---|---|
| Once-daily Aclidinium/Formoterol | 0.257 |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | 0.226 |
| Formoterol BID | 0.200 |
(NCT00706914)
Timeframe: Week 4 of treatment
| Intervention | Liters (Mean) |
|---|---|
| Once-daily Aclidinium/Formoterol | 0.355 |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | 0.319 |
| Formoterol BID | 0.280 |
Sputum Volume Score Scale: 0 = None; 1 = The amount of one teaspoon; 2 = The amount of one tablespoon; 3 = More than one tablespoon (NCT00706914)
Timeframe: Week 4 of treatment
| Intervention | Units on a scale (Mean) |
|---|---|
| Once-daily Aclidinium/Formoterol | -0.17 |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | 0.13 |
| Formoterol BID | -0.00 |
The trough value for each pulmonary function parameter was defined as the mean of the two greatest readings assessed 23 hours and 24 hours following the administration of the morning dose of the previous day (NCT00706914)
Timeframe: Week 4 of treatment
| Intervention | Liters (Mean) |
|---|---|
| Once-daily Aclidinium/Formoterol | 0.097 |
| Morning Aclidinium/Formoterol Plus Evening Formoterol | 0.084 |
| Formoterol BID | 0.118 |
Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h (NCT00736489)
Timeframe: 0, 15min, 30min, 1h, 2h, 4h
| Intervention | Score on a scale (Mean) |
|---|---|
| AZD3199 120 mcg | 0.03 |
| AZD3199 480 mcg | 0.03 |
| AZD3199 1920 mcg | 0.09 |
| Formoterol 9 mcg | 0.00 |
| Formoterol 36 mcg | 0.18 |
| Placebo | 0.00 |
Area under the plasma concentration curve from time 0 to 24 h post-dose (NCT00736489)
Timeframe: 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h
| Intervention | nmol*h/L (Geometric Mean) |
|---|---|
| AZD3199 120 mcg | 1.83 |
| AZD3199 480 mcg | 9.75 |
| AZD3199 1920 mcg | 46.06 |
Maximum plasma concentration of AZD3199 measured (NCT00736489)
Timeframe: 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h
| Intervention | nmol/L (Geometric Mean) |
|---|---|
| AZD3199 120 mcg | 0.99 |
| AZD3199 480 mcg | 5.39 |
| AZD3199 1920 mcg | 24.55 |
Average pulse over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | bpm (Mean) |
|---|---|
| AZD3199 120 mcg | 57.1 |
| AZD3199 480 mcg | 59.0 |
| AZD3199 1920 mcg | 61.9 |
| Formoterol 9 mcg | 58.6 |
| Formoterol 36 mcg | 62.8 |
| Placebo | 58.8 |
Maximum pulse over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | bpm (Mean) |
|---|---|
| AZD3199 120 mcg | 62.1 |
| AZD3199 480 mcg | 65.0 |
| AZD3199 1920 mcg | 66.7 |
| Formoterol 9 mcg | 63.6 |
| Formoterol 36 mcg | 67.3 |
| Placebo | 65.3 |
Average QTc Bazett over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | ms (Mean) |
|---|---|
| AZD3199 120 mcg | 398 |
| AZD3199 480 mcg | 397 |
| AZD3199 1920 mcg | 402 |
| Formoterol 9 mcg | 395 |
| Formoterol 36 mcg | 406 |
| Placebo | 395 |
Maximum QTc Bazett over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | ms (Mean) |
|---|---|
| AZD3199 120 mcg | 412 |
| AZD3199 480 mcg | 407 |
| AZD3199 1920 mcg | 413 |
| Formoterol 9 mcg | 408 |
| Formoterol 36 mcg | 415 |
| Placebo | 408 |
Minimum S-potassium concentration (A well-known effect of beta2-agonists (AZD3199 is a beta2-agonist) is a reduction in serum potassium levels. The minimum value has therefore been evaluated. (NCT00736489)
Timeframe: 0, 15min, 30min,1h, 2h, 4h
| Intervention | mmol/L (Mean) |
|---|---|
| AZD3199 120 mcg | 4.04 |
| AZD3199 480 mcg | 4.03 |
| AZD3199 1920 mcg | 3.98 |
| Formoterol 9 mcg | 4.04 |
| Formoterol 36 mcg | 3.84 |
| Placebo | 4.04 |
Average S-potassium concentration (NCT00736489)
Timeframe: 0, 15min, 30min,1h, 2h, 4h
| Intervention | mmol/L (Mean) |
|---|---|
| AZD3199 120 mcg | 4.22 |
| AZD3199 480 mcg | 4.21 |
| AZD3199 1920 mcg | 4.17 |
| Formoterol 9 mcg | 4.19 |
| Formoterol 36 mcg | 3.99 |
| Placebo | 4.21 |
Average SBP value over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | mmHg (Mean) |
|---|---|
| AZD3199 120 mcg | 121.1 |
| AZD3199 480 mcg | 121.8 |
| AZD3199 1920 mcg | 121.3 |
| Formoterol 9 mcg | 120.9 |
| Formoterol 36 mcg | 122.6 |
| Placebo | 121.3 |
Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h. (NCT00736489)
Timeframe: 0, 15min, 30min, 1h, 2h, 4h
| Intervention | Score on a scale (Mean) |
|---|---|
| AZD3199 120 mcg | 0.06 |
| AZD3199 480 mcg | 0.06 |
| AZD3199 1920 mcg | 0.17 |
| Formoterol 9 mcg | 0.11 |
| Formoterol 36 mcg | 0.47 |
| Placebo | 0.03 |
Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h. (NCT00736489)
Timeframe: 0, 15min, 30min, 1h, 2h, 4h
| Intervention | Score on a scale (Mean) |
|---|---|
| AZD3199 120 mcg | 0.00 |
| AZD3199 480 mcg | 0.02 |
| AZD3199 1920 mcg | 0.04 |
| Formoterol 9 mcg | 0.05 |
| Formoterol 36 mcg | 0.16 |
| Placebo | 0.01 |
Average DBP value over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | mmHg (Mean) |
|---|---|
| AZD3199 120 mcg | 71.4 |
| AZD3199 480 mcg | 72.0 |
| AZD3199 1920 mcg | 71.6 |
| Formoterol 9 mcg | 71.5 |
| Formoterol 36 mcg | 71.0 |
| Placebo | 72.7 |
Residual FEV1 24 h post-dose (NCT00736489)
Timeframe: 22- 26 h post dose
| Intervention | L (Mean) |
|---|---|
| AZD3199 120 mcg | 3.31 |
| AZD3199 480 mcg | 3.35 |
| AZD3199 1920 mcg | 3.40 |
| Formoterol 9 mcg | 3.26 |
| Formoterol 36 mcg | 3.36 |
| Placebo | 3.23 |
FEV1 average effect over 12 h day-time period (NCT00736489)
Timeframe: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h
| Intervention | L (Mean) |
|---|---|
| AZD3199 120 mcg | 3.33 |
| AZD3199 480 mcg | 3.40 |
| AZD3199 1920 mcg | 3.48 |
| Formoterol 9 mcg | 3.40 |
| Formoterol 36 mcg | 3.51 |
| Placebo | 3.20 |
FEV1 average effect over 24 h dosing interval (NCT00736489)
Timeframe: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
| Intervention | L (Mean) |
|---|---|
| AZD3199 120 mcg | 3.31 |
| AZD3199 480 mcg | 3.36 |
| AZD3199 1920 mcg | 3.44 |
| Formoterol 9 mcg | 3.35 |
| Formoterol 36 mcg | 3.46 |
| Placebo | 3.19 |
Maximum SBP value over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | mmHg (Mean) |
|---|---|
| AZD3199 120 mcg | 126.8 |
| AZD3199 480 mcg | 128.3 |
| AZD3199 1920 mcg | 127.4 |
| Formoterol 9 mcg | 127.3 |
| Formoterol 36 mcg | 129.9 |
| Placebo | 126.4 |
Minimum DBP value over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | mmHg (Mean) |
|---|---|
| AZD3199 120 mcg | 67.3 |
| AZD3199 480 mcg | 67.6 |
| AZD3199 1920 mcg | 66.7 |
| Formoterol 9 mcg | 66.9 |
| Formoterol 36 mcg | 66.7 |
| Placebo | 68.8 |
FEV1 average effect over 12 h night-time period (NCT00736489)
Timeframe: 12h, 14h, 18h, 22h, 24h
| Intervention | L (Mean) |
|---|---|
| AZD3199 120 mcg | 3.28 |
| AZD3199 480 mcg | 3.33 |
| AZD3199 1920 mcg | 3.41 |
| Formoterol 9 mcg | 3.30 |
| Formoterol 36 mcg | 3.40 |
| Placebo | 3.19 |
FEV1 at 5 minutes (NCT00736489)
Timeframe: 5min
| Intervention | L (Mean) |
|---|---|
| AZD3199 120 mcg | 3.36 |
| AZD3199 480 mcg | 3.38 |
| AZD3199 1920 mcg | 3.33 |
| Formoterol 9 mcg | 3.37 |
| Formoterol 36 mcg | 3.47 |
| Placebo | 3.13 |
Maximum FEV1 value (NCT00736489)
Timeframe: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
| Intervention | L (Mean) |
|---|---|
| AZD3199 120 mcg | 3.56 |
| AZD3199 480 mcg | 3.62 |
| AZD3199 1920 mcg | 3.70 |
| Formoterol 9 mcg | 3.62 |
| Formoterol 36 mcg | 3.69 |
| Placebo | 3.44 |
Average heart rate over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | bpm (Mean) |
|---|---|
| AZD3199 120 mcg | 58.3 |
| AZD3199 480 mcg | 59.0 |
| AZD3199 1920 mcg | 61.8 |
| Formoterol 9 mcg | 58.6 |
| Formoterol 36 mcg | 62.7 |
| Placebo | 58.1 |
Maximum heart rate over 4 h (NCT00736489)
Timeframe: 0, 30min, 2h, 4h
| Intervention | bpm (Mean) |
|---|---|
| AZD3199 120 mcg | 64.0 |
| AZD3199 480 mcg | 64.1 |
| AZD3199 1920 mcg | 66.9 |
| Formoterol 9 mcg | 63.8 |
| Formoterol 36 mcg | 66.8 |
| Placebo | 64.5 |
Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h (NCT00736489)
Timeframe: 0, 15min, 30min, 1h, 2h, 4h
| Intervention | Score on a scale (Mean) |
|---|---|
| AZD3199 120 mcg | 0.00 |
| AZD3199 480 mcg | 0.01 |
| AZD3199 1920 mcg | 0.02 |
| Formoterol 9 mcg | 0.00 |
| Formoterol 36 mcg | 0.11 |
| Placebo | 0.00 |
Unchanged racemic formoterol in urine was assayed by LC-MS/MS. The lower limit of quantification (LLOQ) for urine was 0.0174 nmol/L expressed as free base. The amounts of unchanged formoterol excreted in urine from 0 to 3 hours (Ae0-3) and from 0 to 12 hours post-dose (Ae0-12) were calculated from the formoterol concentrations in urine and the urine volumes using non-compartmental methods. (NCT00746330)
Timeframe: 0 to 3 hrs and 0-12 hrs
| Intervention | nmol (Least Squares Mean) | |
|---|---|---|
| Ae (0-3) nmol (N=15,17,17) | Ae (0-12) nmol (N=16,17,17) | |
| F12D | 0.42 | 1.33 |
| F12M | 0.52 | 1.50 |
| MFF10 | 0.31 | 1.14 |
All efficacy evaluations were based on spirometry assessments of lung function. PEF is the greatest airflow rate achieved during forced exhalation with lungs fully inflated. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the ATS/ERS standards (NCT00746330)
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
| Intervention | liters (Least Squares Mean) | ||||||
|---|---|---|---|---|---|---|---|
| 5 minutes | 30 minutes | 1 hour (N=32, 31, 29, 31) | 2 hours | 4 hours | 8 hours | 12 hours | |
| F12D | 250.05 | 257.81 | 262.95 | 267.91 | 265.20 | 262.61 | 259.71 |
| F12M | 248.17 | 253.37 | 257.08 | 259.28 | 258.92 | 255.27 | 250.71 |
| MFF10 | 246.65 | 255.69 | 261.18 | 261.45 | 264.68 | 257.96 | 255.48 |
| Placebo | 237.85 | 243.59 | 248.24 | 248.88 | 249.07 | 248.47 | 244.13 |
All efficacy evaluations were based on spirometry assessments of lung function. FVC is the volume (liters) of air that can forcibly be blown out after full inspiration. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the ATS / ERS standards. (NCT00746330)
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
| Intervention | liters (Least Squares Mean) | ||||||
|---|---|---|---|---|---|---|---|
| 5 minutes | 30 minutes | 1 hour (N=32, 31, 29, 31) | 2 hours | 4 hours | 8 hours | 12 hours | |
| F12D | 2.09 | 2.11 | 2.15 | 2.14 | 2.12 | 2.10 | 2.09 |
| F12M | 2.09 | 2.11 | 2.09 | 2.08 | 2.08 | 2.09 | 2.05 |
| MFF10 | 2.09 | 2.12 | 2.14 | 2.11 | 2.12 | 2.09 | 2.07 |
| Placebo | 2.08 | 2.08 | 2.10 | 2.11 | 2.11 | 2.09 | 2.06 |
All efficacy evaluations were based on spirometry assessments of lung function. FEV1 is the maximum amount of air expired in one second. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the (ATS / ERS) standards. (NCT00746330)
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
| Intervention | liters (Least Squares Mean) | ||||||
|---|---|---|---|---|---|---|---|
| 5 minutes | 30 minutes | 1 hour (N=32, 31, 29, 31) | 2 hours | 4 hours | 8 hours | 12 hours | |
| F12D | 1.77 | 1.82 | 1.86 | 1.85 | 1.84 | 1.79 | 1.76 |
| F12M | 1.77 | 1.80 | 1.80 | 1.79 | 1.79 | 1.75 | 1.71 |
| MFF10 | 1.74 | 1.79 | 1.81 | 1.81 | 1.81 | 1.76 | 1.72 |
| Placebo | 1.68 | 1.69 | 1.72 | 1.73 | 1.72 | 1.70 | 1.66 |
Unchanged racemic formoterol in plasma was assayed by LC-MS/MS. The lower limit of quantification (LLOQ) for plasma was 1.45 pmol/L. No non-compartmental PK analysis was performed. (NCT00746330)
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
| Intervention | pmol/L (Mean) | |||||
|---|---|---|---|---|---|---|
| Pre-Dose (N count MFF=15,F12M=17,F12D=16) | 5-10 minutes (N=16, 17, 17) | 30 minutes - 2 hours (N=16,17,17) | 2 hours - 4 hours (N= 16, 17, 17) | 4 hours - 8 hours (N= 16, 17, 17) | 8 hours - 12 hours (N= 16, 16, 17) | |
| F12D | 0 | 18.56 | 23.1 | 17.4 | 11.3 | 6.83 |
| F12M | 0 | 16.3 | 24.7 | 17.7 | 11.0 | 6.66 |
| MFF10 | 0 | 13.1 | 27.5 | 22.4 | 12.3 | 7.74 |
For FEV1 AUC(0-12h) the trapezoidal rule was applied using planned time measurements to calculate the AUC up to and including the last measurement recorded before intake of rescue medication. The AUC was standardized by dividing by the length of time for which measurements of FEV1 were included in the calculation of the AUC thus adjusting for subjects who were unable to complete the measurements during the 12-hour observation period and without inhaling rescue medication. The unit of the AUC was in L, being a weighted average of the acceptable FEV1 measurements recorded over 12 hours post dose (NCT00746330)
Timeframe: From 0 to 12 Hours (0-12h) post-dose, after each treatment administered (approximately 1 treatment a week for 4 weeks of treatment).
| Intervention | liters (Least Squares Mean) |
|---|---|
| MFF10 | 1.77 |
| F12M | 1.77 |
| F12D | 1.80 |
| Placebo | 1.71 |
"linear regression slope of breathlessness - time for arformoterol and for normal saline will be compared between treadmill and cycle exercise~The higher the number the worse the shortness of breath" (NCT00754546)
Timeframe: After one dose
| Intervention | breathlessness units/min (Least Squares Mean) |
|---|---|
| Treadmill Exercise With the Active Comparator | 1.27 |
| Cycle Exercise With the Active Comparator | 1.79 |
| Treadmill Exercise With the Placebo Comparator | 1.42 |
| Cycle Exercise With the Placebo Comparator | 1.49 |
Participants were asked to exercise until symptom limitation (NCT00754546)
Timeframe: After one dose
| Intervention | seconds (Mean) |
|---|---|
| Treadmill Exercise With the Active Comparator | 490 |
| Cycle Exercise With the Active Comparator | 333 |
| Treadmill Exercise With the Placebo Comparator | 472 |
| Cycle Exercise With the Placebo Comparator | 362 |
Change from baseline in Forced Vital Capacity (FVC) after 1 week on Brovana or Placebo. (Change = 1 week - baseline) (NCT00773786)
Timeframe: baseline and 1 week
| Intervention | Liters (Mean) | |
|---|---|---|
| Trough to trough | Peak to peak | |
| Brovana (Arformoterol) | 0120 | 0.080 |
| Placebo | 0.000 | -0.062 |
Change from baseline in Inspiratory Capacity (IC) after 1 week on Brovana or Placebo (measured 2 hours post dose). (Change = 1 week - baseline). (NCT00773786)
Timeframe: baseline and 2 hours after dosing
| Intervention | Liters (Mean) | |
|---|---|---|
| Trough to trough | Peak to peak | |
| Brovana (Arformoterol) | 0.001 | 0.113 |
| Placebo | -0.019 | -0.004 |
Change from baseline in Forced Expiratory Volume in 1 second (FEV1) after 1 week on Brovana or Placebo (measured 2 hours post dose). (Change = 1 week - baseline) (NCT00773786)
Timeframe: baseline and 1 week
| Intervention | Liters (Mean) | |
|---|---|---|
| Trough to trough | Peak to peak | |
| Brovana (Arformoterol) | 0.069 | 0.121 |
| Placebo | 0.010 | 0.023 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). (NCT00793624)
Timeframe: Baseline, Week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 40.415 |
| Olo 5 mcg qd | 38.545 |
| Olo 10 mcg qd | 36.850 |
| Form 12 mcg | 40.431 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. (NCT00793624)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Days (Mean) |
|---|---|
| Placebo (Tiotropium) | 143 |
| Placebo (Non-tiotropium) | 268 |
| Olo 5 mcg qd (Tiotropium) | 136 |
| Olo 5 mcg qd (Non-tiotropium) | 189 |
| Olo 10 mcg qd (Tiotropium) | 134 |
| Olo 10 mcg qd(Non-tiotropium) | 209 |
| Form 12 mcg (Tiotropium) | 223 |
| Form 12 mcg (Non-tiotropium) | 310 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. (NCT00793624)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Days (Mean) |
|---|---|
| Placebo (Tiotropium) | NA |
| Placebo (Non-tiotropium) | NA |
| Olo 5 mcg qd (Tiotropium) | NA |
| Olo 5 mcg qd (Non-tiotropium) | NA |
| Olo 10 mcg qd (Tiotropium) | NA |
| Olo 10 mcg qd(Non-tiotropium) | NA |
| Form 12 mcg (Tiotropium) | NA |
| Form 12 mcg (Non-tiotropium) | NA |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. (NCT00793624)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Days (Mean) |
|---|---|
| Placebo (Tiotropium) | 150 |
| Placebo (Non-tiotropium) | 296 |
| Olo 5 mcg qd (Tiotropium) | 239 |
| Olo 5 mcg qd (Non-tiotropium) | 244 |
| Olo 10 mcg qd (Tiotropium) | 175 |
| Olo 10 mcg qd(Non-tiotropium) | 302 |
| Form 12 mcg (Tiotropium) | 280 |
| Form 12 mcg (Non-tiotropium) | 270 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.027 |
| Olo 5 mcg qd | 0.056 |
| Olo 10 mcg qd | 0.048 |
| Form 12 mcg | 0.033 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.019 |
| Olo 5 mcg qd | 0.046 |
| Olo 10 mcg qd | 0.026 |
| Form 12 mcg | 0.023 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.019 |
| Olo 5 mcg qd | 0.068 |
| Olo 10 mcg qd | 0.060 |
| Form 12 mcg | 0.061 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.056 |
| Olo 5 mcg qd | 0.021 |
| Olo 10 mcg qd | 0.028 |
| Form 12 mcg | -0.002 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.023 |
| Olo 5 mcg qd | 0.023 |
| Olo 10 mcg qd | 0.026 |
| Form 12 mcg | 0.021 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.020 |
| Olo 5 mcg qd | 0.020 |
| Olo 10 mcg qd | 0.017 |
| Form 12 mcg | 0.004 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.065 |
| Olo 5 mcg qd | 0.003 |
| Olo 10 mcg qd | -0.009 |
| Form 12 mcg | -0.006 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.037 |
| Olo 5 mcg qd | 0.049 |
| Olo 10 mcg qd | 0.041 |
| Form 12 mcg | 0.042 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.018 |
| Olo 5 mcg qd | 0.079 |
| Olo 10 mcg qd | 0.087 |
| Form 12 mcg | 0.068 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.060 |
| Olo 5 mcg qd | 0.066 |
| Olo 10 mcg qd | 0.078 |
| Form 12 mcg | 0.063 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.042 |
| Olo 5 mcg qd | 0.110 |
| Olo 10 mcg qd | 0.119 |
| Form 12 mcg | 0.126 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.018 |
| Olo 5 mcg qd | 0.038 |
| Olo 10 mcg qd | 0.064 |
| Form 12 mcg | 0.001 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.019 |
| Olo 5 mcg qd | 0.080 |
| Olo 10 mcg qd | 0.084 |
| Form 12 mcg | 0.077 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.940 |
| Olo 5 mcg qd | 2.035 |
| Olo 10 mcg qd | 2.324 |
| Form 12 mcg | 2.047 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.995 |
| Olo 5 mcg qd | 1.566 |
| Olo 10 mcg qd | 1.660 |
| Form 12 mcg | 1.753 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. (NCT00793624)
Timeframe: Baseline to end of study at week 48 visit
| Intervention | Number of COPD ex. per patient year (Mean) |
|---|---|
| Placebo | 0.5684 |
| Olo 5 mcg qd | 0.7117 |
| Olo 10 mcg qd | 0.6946 |
| Form 12 mcg | 0.5098 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. (NCT00793624)
Timeframe: Baseline to end of study at week 48 visit
| Intervention | Number of COPD ex. per patient year (Mean) |
|---|---|
| Placebo | 0.0554 |
| Olo 5 mcg qd | 0.1043 |
| Olo 10 mcg qd | 0.1324 |
| Form 12 mcg | 0.0570 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. (NCT00793624)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Number of COPD ex. per patient year (Mean) |
|---|---|
| Placebo | 0.4765 |
| Olo 5 mcg qd | 0.5537 |
| Olo 10 mcg qd | 0.5114 |
| Form 12 mcg | 0.3721 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00793624)
Timeframe: Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.3 |
| Olo 5 mcg qd | 3.0 |
| Olo 10 mcg qd | 2.9 |
| Form 12 mcg | 3.0 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00793624)
Timeframe: Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.1 |
| Olo 5 mcg qd | 2.9 |
| Olo 10 mcg qd | 2.9 |
| Form 12 mcg | 3.0 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00793624)
Timeframe: Week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.1 |
| Olo 5 mcg qd | 3.0 |
| Olo 10 mcg qd | 2.9 |
| Form 12 mcg | 2.9 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.028 |
| Olo 5 mcg qd | 0.087 |
| Olo 10 mcg qd | 0.086 |
| Form 12 mcg | 0.052 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00793624)
Timeframe: Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.4 |
| Olo 5 mcg qd | 3.0 |
| Olo 10 mcg qd | 3.1 |
| Form 12 mcg | 3.1 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.068 |
| Olo 5 mcg qd | 0.216 |
| Olo 10 mcg qd | 0.225 |
| Form 12 mcg | 0.236 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.100 |
| Olo 5 mcg qd | 0.277 |
| Olo 10 mcg qd | 0.250 |
| Form 12 mcg | 0.290 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.082 |
| Olo 5 mcg qd | 0.247 |
| Olo 10 mcg qd | 0.241 |
| Form 12 mcg | 0.256 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.207 |
| Olo 5 mcg qd | 0.379 |
| Olo 10 mcg qd | 0.414 |
| Form 12 mcg | 0.424 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.193 |
| Olo 5 mcg qd | 0.344 |
| Olo 10 mcg qd | 0.371 |
| Form 12 mcg | 0.416 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). (NCT00793624)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 41.068 |
| Olo 5 mcg qd | 38.627 |
| Olo 10 mcg qd | 37.674 |
| Form 12 mcg | 40.116 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.202 |
| Olo 5 mcg qd | 0.411 |
| Olo 10 mcg qd | 0.433 |
| Form 12 mcg | 0.467 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.053 |
| Olo 5 mcg qd | 0.192 |
| Olo 10 mcg qd | 0.193 |
| Form 12 mcg | 0.215 |
Mean number of puffs of rescue medication used per day (daytime/nighttime/total) (NCT00793624)
Timeframe: Week 24
| Intervention | Number of puffs (Mean) | ||
|---|---|---|---|
| Daytime | Nighttime | Total | |
| Form 12 mcg | 1.217 | 1.701 | 2.917 |
| Olo 10 mcg qd | 1.037 | 1.471 | 2.488 |
| Olo 5 mcg qd | 0.961 | 1.449 | 2.399 |
| Placebo | 1.364 | 2.051 | 3.390 |
Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline. (NCT00793624)
Timeframe: Week 24
| Intervention | L/min (Mean) | |
|---|---|---|
| morning PEFR (N=214, 212, 216, 218) | evening PEFR (N=215, 211, 215, 221) | |
| Form 12 mcg | 214.070 | 220.129 |
| Olo 10 mcg qd | 211.428 | 220.727 |
| Olo 5 mcg qd | 211.496 | 219.977 |
| Placebo | 196.429 | 202.256 |
Occurence of cardiac disorders and investigations related to treatment. (NCT00793624)
Timeframe: 48 weeks
| Intervention | percentage of participants (Number) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Tachycardia | Arrhythmia | Atrial fibrillation | Atrioventricular block | Atrioventricular block first degree | Bundle branch block right | Palpitations | Ventricular extrasystoles | Electrocardiogram QT prolonged | Electrocardiogram T wave inversion | |
| Form 12 mcg | 0.9 | 0.0 | 0.4 | 0.0 | 0.4 | 0.0 | 0.4 | 0.0 | 0.4 | 0.4 |
| Olo 10 mcg qd | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| Olo 5 mcg qd | 0.0 | 0.4 | 0.0 | 0.0 | 0.0 | 0.4 | 0.0 | 0.0 | 0.4 | 0.0 |
| Placebo | 0.4 | 0.0 | 0.4 | 0.4 | 0.0 | 0.0 | 0.4 | 0.4 | 0.0 | 0.0 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.046 |
| Olo 5 mcg qd | 0.065 |
| Olo 10 mcg qd | 0.085 |
| Form 12 mcg | 0.090 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.061 |
| Olo 5 mcg qd | 0.022 |
| Olo 10 mcg qd | -0.002 |
| Form 12 mcg | 0.006 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). (NCT00793624)
Timeframe: Baseline, Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 42.105 |
| Olo 5 mcg qd | 39.320 |
| Olo 10 mcg qd | 36.961 |
| Form 12 mcg | 40.351 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model. (NCT00793624)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Placebo | 41.639 |
| Olo 5 mcg qd | 38.794 |
| Olo 10 mcg qd | 38.205 |
| Form 12 mcg | 40.391 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.268 |
| Olo 5 mcg qd | 0.454 |
| Olo 10 mcg qd | 0.474 |
| Form 12 mcg | 0.551 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.194 |
| Olo 5 mcg qd | 0.382 |
| Olo 10 mcg qd | 0.432 |
| Form 12 mcg | 0.450 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.081 |
| Olo 5 mcg qd | 0.248 |
| Olo 10 mcg qd | 0.234 |
| Form 12 mcg | 0.264 |
Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means. (NCT00793624)
Timeframe: within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Olo 5 mcg qd | 4.179 |
| Olo 10 mcg qd | 7.246 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.003 |
| Olo 5 mcg qd | 0.176 |
| Olo 10 mcg qd | 0.167 |
| Form 12 mcg | 0.182 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.015 |
| Olo 5 mcg qd | 0.201 |
| Olo 10 mcg qd | 0.181 |
| Form 12 mcg | 0.221 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.009 |
| Olo 5 mcg qd | 0.142 |
| Olo 10 mcg qd | 0.156 |
| Form 12 mcg | 0.168 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.023 |
| Olo 5 mcg qd | 0.122 |
| Olo 10 mcg qd | 0.123 |
| Form 12 mcg | 0.149 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.001 |
| Olo 5 mcg qd | 0.178 |
| Olo 10 mcg qd | 0.161 |
| Form 12 mcg | 0.194 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.023 |
| Olo 5 mcg qd | 0.233 |
| Olo 10 mcg qd | 0.278 |
| Form 12 mcg | 0.300 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.076 |
| Olo 5 mcg qd | 0.299 |
| Olo 10 mcg qd | 0.311 |
| Form 12 mcg | 0.383 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.037 |
| Olo 5 mcg qd | 0.220 |
| Olo 10 mcg qd | 0.252 |
| Form 12 mcg | 0.279 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.016 |
| Olo 5 mcg qd | 0.196 |
| Olo 10 mcg qd | 0.219 |
| Form 12 mcg | 0.260 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00793624)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.016 |
| Olo 5 mcg qd | 0.252 |
| Olo 10 mcg qd | 0.265 |
| Form 12 mcg | 0.326 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.412 |
| Olo 5 mcg qd | 1.792 |
| Olo 10 mcg qd | 1.955 |
| Form 12 mcg | 1.805 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 18
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.665 |
| Olo 5 mcg qd | 1.897 |
| Olo 10 mcg qd | 2.099 |
| Form 12 mcg | 1.689 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 2.046 |
| Olo 5 mcg qd | 2.234 |
| Olo 10 mcg qd | 2.068 |
| Form 12 mcg | 1.818 |
This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Placebo | 1.471 |
| Olo 5 mcg qd | 1.980 |
| Olo 10 mcg qd | 1.996 |
| Form 12 mcg | 1.827 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 32
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.732 |
| Olo 5 mcg qd | 1.898 |
| Olo 10 mcg qd | 1.698 |
| Form 12 mcg | 1.966 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00793624)
Timeframe: Baseline, Week 40
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.952 |
| Olo 5 mcg qd | 1.839 |
| Olo 10 mcg qd | 1.887 |
| Form 12 mcg | 1.575 |
Mean number of puffs of rescue medication used per day (daytime/nighttime/total) (NCT00796653)
Timeframe: Week 24
| Intervention | Number of puffs (Mean) | ||
|---|---|---|---|
| Daytime | Nighttime | Total | |
| Form 12 mcg | 0.967 | 1.393 | 2.353 |
| Olo 10 mcg qd | 0.923 | 1.348 | 2.277 |
| Olo 5 mcg qd | 1.036 | 1.435 | 2.470 |
| Placebo | 1.189 | 1.713 | 2.893 |
Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline. (NCT00796653)
Timeframe: Week 24
| Intervention | L/min (Mean) | |
|---|---|---|
| morning PEFR (N=225, 227, 226, 224) | evening PEFR (N=224, 223, 227, 222) | |
| Form 12 mcg | 211.038 | 218.321 |
| Olo 10 mcg qd | 217.660 | 225.380 |
| Olo 5 mcg qd | 210.496 | 219.905 |
| Placebo | 196.789 | 202.505 |
Occurence of cardiac disorders and investigations related to treatment. (NCT00796653)
Timeframe: 48 weeks
| Intervention | percentage of participants (Number) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Atrial fibrillation | Sinus tachycardia | Acute coronary syndrome | Acute myocardial infarction | Angina unstable | Myocardial infarction | Ventricular extrasystoles | Alanine aminotransferase increased | Aspartate aminotransferase increased | Blood creatine phosphokinase increased | Electrocardiogram ST segment depression | Electrocardiogram T wave inversion | Gamma-glutamyltransferase increased | |
| Form 12 mcg | 0.0 | 0.9 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 0.0 | 0.4 | 0.4 | 0.0 | 0.0 | 0.0 |
| Olo 10 mcg qd | 0.9 | 0.0 | 0.0 | 0.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| Olo 5 mcg qd | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.4 | 0.0 | 0.0 | 0.0 | 0.4 | 0.0 | 0.0 |
| Placebo | 0.9 | 0.0 | 0.4 | 0.0 | 0.4 | 0.4 | 0.4 | 0.4 | 0.0 | 0.0 | 0.0 | 0.4 | 0.4 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.014 |
| Olo 5 mcg qd | 0.113 |
| Olo 10 mcg qd | 0.101 |
| Form 12 mcg | 0.085 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.069 |
| Olo 5 mcg qd | 0.012 |
| Olo 10 mcg qd | 0.032 |
| Form 12 mcg | -0.031 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.016 |
| Olo 5 mcg qd | 0.071 |
| Olo 10 mcg qd | 0.105 |
| Form 12 mcg | 0.037 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.007 |
| Olo 5 mcg qd | 0.081 |
| Olo 10 mcg qd | 0.063 |
| Form 12 mcg | 0.036 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.044 |
| Olo 5 mcg qd | 0.023 |
| Olo 10 mcg qd | 0.019 |
| Form 12 mcg | -0.005 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.030 |
| Olo 5 mcg qd | 0.118 |
| Olo 10 mcg qd | 0.173 |
| Form 12 mcg | 0.111 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.014 |
| Olo 5 mcg qd | 0.084 |
| Olo 10 mcg qd | 0.107 |
| Form 12 mcg | 0.064 |
Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.041 |
| Olo 5 mcg qd | 0.062 |
| Olo 10 mcg qd | 0.062 |
| Form 12 mcg | 0.070 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.036 |
| Olo 5 mcg qd | 0.047 |
| Olo 10 mcg qd | 0.068 |
| Form 12 mcg | 0.034 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.060 |
| Olo 5 mcg qd | -0.016 |
| Olo 10 mcg qd | -0.001 |
| Form 12 mcg | -0.024 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.043 |
| Olo 5 mcg qd | 0.019 |
| Olo 10 mcg qd | 0.041 |
| Form 12 mcg | 0.013 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.016 |
| Olo 5 mcg qd | 0.053 |
| Olo 10 mcg qd | 0.103 |
| Form 12 mcg | 0.033 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.055 |
| Olo 5 mcg qd | -0.003 |
| Olo 10 mcg qd | 0.014 |
| Form 12 mcg | -0.013 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.039 |
| Olo 5 mcg qd | 0.023 |
| Olo 10 mcg qd | 0.034 |
| Form 12 mcg | 0.009 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00796653)
Timeframe: Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.4 |
| Olo 5 mcg qd | 3.1 |
| Olo 10 mcg qd | 3.2 |
| Form 12 mcg | 3.1 |
Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means. (NCT00796653)
Timeframe: within 2 hours before first study drug administration and 10 minutes post-dose at week 6, 12 and 18
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Olo 5 mcg qd | 3.920 |
| Olo 10 mcg qd | 6.977 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.008 |
| Olo 5 mcg qd | 0.138 |
| Olo 10 mcg qd | 0.167 |
| Form 12 mcg | 0.163 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.021 |
| Olo 5 mcg qd | 0.181 |
| Olo 10 mcg qd | 0.214 |
| Form 12 mcg | 0.183 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.013 |
| Olo 5 mcg qd | 0.116 |
| Olo 10 mcg qd | 0.140 |
| Form 12 mcg | 0.137 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.025 |
| Olo 5 mcg qd | 0.093 |
| Olo 10 mcg qd | 0.116 |
| Form 12 mcg | 0.104 |
Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.010 |
| Olo 5 mcg qd | 0.162 |
| Olo 10 mcg qd | 0.181 |
| Form 12 mcg | 0.174 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.006 |
| Olo 5 mcg qd | 0.235 |
| Olo 10 mcg qd | 0.253 |
| Form 12 mcg | 0.280 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.082 |
| Olo 5 mcg qd | 0.312 |
| Olo 10 mcg qd | 0.332 |
| Form 12 mcg | 0.348 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.012 |
| Olo 5 mcg qd | 0.212 |
| Olo 10 mcg qd | 0.225 |
| Form 12 mcg | 0.253 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.036 |
| Olo 5 mcg qd | 0.182 |
| Olo 10 mcg qd | 0.201 |
| Form 12 mcg | 0.184 |
Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.027 |
| Olo 5 mcg qd | 0.277 |
| Olo 10 mcg qd | 0.276 |
| Form 12 mcg | 0.307 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.080 |
| Olo 5 mcg qd | 1.742 |
| Olo 10 mcg qd | 1.747 |
| Form 12 mcg | 1.499 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 18
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.0454 |
| Olo 5 mcg qd | 1.470 |
| Olo 10 mcg qd | 1.537 |
| Form 12 mcg | 1.579 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.102 |
| Olo 5 mcg qd | 1.504 |
| Olo 10 mcg qd | 1.521 |
| Form 12 mcg | 1.703 |
This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Placebo | 1.471 |
| Olo 5 mcg qd | 1.980 |
| Olo 10 mcg qd | 1.996 |
| Form 12 mcg | 1.827 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 32
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.168 |
| Olo 5 mcg qd | 1.658 |
| Olo 10 mcg qd | 1.522 |
| Form 12 mcg | 1.477 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 40
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.064 |
| Olo 5 mcg qd | 1.377 |
| Olo 10 mcg qd | 1.545 |
| Form 12 mcg | 1.178 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.113 |
| Olo 5 mcg qd | 1.510 |
| Olo 10 mcg qd | 1.831 |
| Form 12 mcg | 1.280 |
Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement). (NCT00796653)
Timeframe: Baseline, Week 6
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.980 |
| Olo 5 mcg qd | 1.417 |
| Olo 10 mcg qd | 1.686 |
| Form 12 mcg | 1.444 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. (NCT00796653)
Timeframe: Baseline to end of study at week 48 visit
| Intervention | Number of COPD ex. per patient year (Mean) |
|---|---|
| Placebo | 0.6890 |
| Olo 5 mcg qd | 0.5409 |
| Olo 10 mcg qd | 0.5947 |
| Form 12 mcg | 0.7325 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. (NCT00796653)
Timeframe: Baseline to end of study at week 48 visit
| Intervention | Number of COPD ex. per patient year (Mean) |
|---|---|
| Placebo | 0.0986 |
| Olo 5 mcg qd | 0.0781 |
| Olo 10 mcg qd | 0.0993 |
| Form 12 mcg | 0.1025 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. (NCT00796653)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Number of COPD ex. per patient year (Mean) |
|---|---|
| Placebo | 0.5548 |
| Olo 5 mcg qd | 0.4128 |
| Olo 10 mcg qd | 0.4351 |
| Form 12 mcg | 0.5415 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00796653)
Timeframe: Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.3 |
| Olo 5 mcg qd | 3.1 |
| Olo 10 mcg qd | 3.0 |
| Form 12 mcg | 3.0 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00796653)
Timeframe: Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.3 |
| Olo 5 mcg qd | 3.1 |
| Olo 10 mcg qd | 3.1 |
| Form 12 mcg | 3.1 |
Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse). (NCT00796653)
Timeframe: Week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 3.2 |
| Olo 5 mcg qd | 3.2 |
| Olo 10 mcg qd | 3.0 |
| Form 12 mcg | 3.2 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.064 |
| Olo 5 mcg qd | 0.206 |
| Olo 10 mcg qd | 0.232 |
| Form 12 mcg | 0.228 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.099 |
| Olo 5 mcg qd | 0.260 |
| Olo 10 mcg qd | 0.278 |
| Form 12 mcg | 0.253 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.060 |
| Olo 5 mcg qd | 0.183 |
| Olo 10 mcg qd | 0.211 |
| Form 12 mcg | 0.203 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.052 |
| Olo 5 mcg qd | 0.163 |
| Olo 10 mcg qd | 0.178 |
| Form 12 mcg | 0.170 |
Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.066 |
| Olo 5 mcg qd | 0.235 |
| Olo 10 mcg qd | 0.248 |
| Form 12 mcg | 0.242 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.171 |
| Olo 5 mcg qd | 0.386 |
| Olo 10 mcg qd | 0.396 |
| Form 12 mcg | 0.436 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.247 |
| Olo 5 mcg qd | 0.480 |
| Olo 10 mcg qd | 0.476 |
| Form 12 mcg | 0.495 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.189 |
| Olo 5 mcg qd | 0.371 |
| Olo 10 mcg qd | 0.369 |
| Form 12 mcg | 0.397 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.137 |
| Olo 5 mcg qd | 0.325 |
| Olo 10 mcg qd | 0.352 |
| Form 12 mcg | 0.329 |
Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.196 |
| Olo 5 mcg qd | 0.443 |
| Olo 10 mcg qd | 0.417 |
| Form 12 mcg | 0.450 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). (NCT00796653)
Timeframe: Baseline, Week 12
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 42.679 |
| Olo 5 mcg qd | 40.054 |
| Olo 10 mcg qd | 40.190 |
| Form 12 mcg | 39.521 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). (NCT00796653)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 42.120 |
| Olo 5 mcg qd | 38.970 |
| Olo 10 mcg qd | 38.597 |
| Form 12 mcg | 40.704 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model. (NCT00796653)
Timeframe: Baseline, Week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 41.639 |
| Olo 5 mcg qd | 38.794 |
| Olo 10 mcg qd | 38.205 |
| Form 12 mcg | 40.391 |
Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). (NCT00796653)
Timeframe: Baseline, Week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 39.914 |
| Olo 5 mcg qd | 39.562 |
| Olo 10 mcg qd | 38.824 |
| Form 12 mcg | 40.025 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. (NCT00796653)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Days (Mean) |
|---|---|
| Placebo (Tiotropium) | 173 |
| Placebo (Non-tiotropium) | 177 |
| Olo 5 mcg qd (Tiotropium) | 252 |
| Olo 5 mcg qd (Non-tiotropium) | 270 |
| Olo 10 mcg qd (Tiotropium) | 252 |
| Olo 10 mcg qd(Non-tiotropium) | 234 |
| Form 12 mcg (Tiotropium) | 149 |
| Form 12 mcg (Non-tiotropium) | 232 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. (NCT00796653)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Days (Mean) |
|---|---|
| Placebo (Tiotropium) | NA |
| Placebo (Non-tiotropium) | NA |
| Olo 5 mcg qd (Tiotropium) | NA |
| Olo 5 mcg qd (Non-tiotropium) | NA |
| Olo 10 mcg qd (Tiotropium) | NA |
| Olo 10 mcg qd(Non-tiotropium) | NA |
| Form 12 mcg (Tiotropium) | NA |
| Form 12 mcg (Non-tiotropium) | 368.0 |
Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. (NCT00796653)
Timeframe: Baseline to end of study at 48 weeks.
| Intervention | Days (Mean) |
|---|---|
| Placebo (Tiotropium) | 176 |
| Placebo (Non-tiotropium) | 214 |
| Olo 5 mcg qd (Tiotropium) | 264 |
| Olo 5 mcg qd (Non-tiotropium) | 312 |
| Olo 10 mcg qd (Tiotropium) | 324 |
| Olo 10 mcg qd(Non-tiotropium) | 327 |
| Form 12 mcg (Tiotropium) | 190 |
| Form 12 mcg (Non-tiotropium) | 325 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.041 |
| Olo 5 mcg qd | 0.018 |
| Olo 10 mcg qd | 0.052 |
| Form 12 mcg | 0.024 |
Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. (NCT00796653)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.036 |
| Olo 5 mcg qd | 0.013 |
| Olo 10 mcg qd | 0.049 |
| Form 12 mcg | 0.015 |
"Following screening, each subject was randomized to a sequence of 5 dosing periods (Doses A, B, C, D, and E). Each period was separated by a 3- to 14-day washout interval.~The dosing formulations were as follows:~Dose A = placebo Dose B = TrIP-2D (100 μg TrCl formulated in leucine and DPPC) Dose C = TrIP-2SS (100 μg TrCl formulated in leucine and sodium saccharin) Dose D = TrIP-2D (400 μg TrCl) Dose E = TrIP-2SS (100 μg TrCl) + Foradil (12 μg formoterol fumarate) FEV1 (L)was measured at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose." (NCT00801684)
Timeframe: 15 minutes to 24 hours post-treatment
| Intervention | Liters (Mean) |
|---|---|
| TrIP-2SS (100mcg) | 1.707 |
| TrIP-2SS (100mcg) + Foradil (12mcg) | 1.696 |
| TrIP-2D (100mcg) | 1.672 |
| TrIP-2D (400mcg) | 1.676 |
| Placebo | 1.508 |
Response was defined as the number of subjects reporting a post-treatment FEV1 of ≥12% (or 200 mL) above baseline. (NCT00801684)
Timeframe: Up to 24 hours post-treatment
| Intervention | Participants (Number) |
|---|---|
| TrIP-2SS (100mcg) | 23 |
| TrIP-2SS (100mcg) + Foradil (12mcg) | 22 |
| TrIP-2D (100mcg) | 22 |
| TrIP-2D (400mcg) | 21 |
| Placebo | 14 |
Tmax is reported as median (range) of hours to reach maximum trospium concentration in plasma. (NCT00801684)
Timeframe: up to 24 hours post-treatment
| Intervention | Hours (Median) |
|---|---|
| TrIP-2D (100mcg) | 0.08 |
| TrIP-2SS (100mcg) | 0.08 |
| TrIP-2D (400mcg) | 0.08 |
| TrIP-2SS (100mcg) + Foradil (12mcg) | 0.08 |
A protocol-defined exacerbation of COPD was defined as an increase in respiratory symptoms (classically, increased shortness of breath, increased sputum production, and/or increased sputum purulence) that necessitates any change in baseline medication other than bronchodilators (e.g., anti-inflammatory agents, antibiotics, supplemental oxygen therapy, etc) or causes the subject to require additional medical attention (i.e., emergency room visit or hospitalization). (NCT00909779)
Timeframe: 0-12 months
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| Overall | 1 COPD event | 2 COPD events | 3 or more COPD events | |
| Experimental: Arformoterol 15 Mcg Twice Daily | 122 | 71 | 29 | 22 |
| Placebo Comparator: Placebo Twice Daily | 132 | 72 | 34 | 26 |
The SGRQ assessed health status and consisted of 3 component scores (Symptoms, Activity, and Impacts) as well as a total score. Items were scored in accordance with the developer's guidelines. Scores were expressed as a percentage of overall impairment, where 100 represented worst possible health status and 0 indicated best possible health status. The SGRQ was assessed pre-dose at baseline, months 3, 6 and 12 or the end of study (EOS). Visit 2 was defined as baseline. A change from baseline in the Total Score of ≥ 4 units is considered the minimal clinically important difference (MCID) for SGRQ. (NCT00909779)
Timeframe: Baseline and on treatment at months 3, 6 and 12 (or early termination)
| Intervention | Score (Least Squares Mean) | |||
|---|---|---|---|---|
| Month 3 (n=276,308) | Month 6 (n=233,287) | Month 12 (n=199,236) | EOS (n=375,379) | |
| Experimental: Arformoterol 15 Mcg Twice Daily | -3.876 | -4.054 | -4.796 | -3.231 |
| Placebo Comparator: Placebo Twice Daily | -1.544 | -1.855 | -2.673 | -0.587 |
"Percent predicted FEV1: measured FEV1 as a percent of the predicted values for the patients of similar characteristics (height, age, sex, and sometimes race and weight). Best FEV1 percent predicted was measured at Visit 1 (screening), pre-dose at baseline, months 3, 6, 9 and 12/EOS, as described for FEV1." (NCT00909779)
Timeframe: Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)
| Intervention | Liter (Least Squares Mean) | ||||
|---|---|---|---|---|---|
| Month 3 (n=289,331) | Month 6 (n=248,300) | Month 9 (n=223,268) | Month 12 (n=206,252) | EOS (n=380,391) | |
| Experimental: Arformoterol 15 Mcg Twice Daily | 3.480 | 3.460 | 3.651 | 2.662 | 2.936 |
| Placebo Comparator: Placebo Twice Daily | 1.410 | 1.768 | 2.606 | 1.678 | 2.156 |
Survival status at the end of the study will be determined for each subject. The proportion of subjects dead and the annual event rate will be summarized by treatment. (NCT00909779)
Timeframe: 0-12 months
| Intervention | participants (Number) |
|---|---|
| Placebo Comparator: Placebo Twice Daily | 10 |
| Experimental: Arformoterol 15 Mcg Twice Daily | 12 |
"TEAEs were defined as: 1) adverse events that occurred on or after the date of first dose of study medication, 2) adverse events with a missing start date and a stop date on or after the date of first does of study medication, or 3) adverse events with both a missing start and stop date.~The frequency and percentage of subjects with TEAEs were summarized. At each level of summarization, a subject was counted only once for each AE he/she experienced within that level. The percentage of subjects having had at least 1 AE at each level was calculated." (NCT00909779)
Timeframe: 0-12 months
| Intervention | participants (Number) |
|---|---|
| Placebo Comparator: Placebo Twice Daily | 287 |
| Experimental: Arformoterol 15 Mcg Twice Daily | 306 |
COPD exacerbation: an increase in COPD symptoms that necessitated any change in baseline medication (bronchodilators,anti-inflammatory agents, antibiotics, supplemental oxygen therapy, etc.).Hospitalization: any inpatient admission or any emergency department visit > 24 hours in duration. Hospice was considered hospitalization.COPD exacerbation related hospitalization: hospitalization that was due to 1) COPD exacerbation or 2) a COPD exacerbation preceded, or occurred concomitantly with the onset of, the event for which the subject was hospitalized.Respiratory-related death: For each death the Primary Investigator designated a 'probable cause', which was the primary condition that precipitated the terminal events that were the immediate cause of death. If a probable cause could not be ascertained, the cause of death was considered 'UNKNOWN'. Cause other than 'UNKNOWN' was categorized as either respiratory or non-respiratory. Deaths of 'UNKNOWN' cause were counted as primary events. (NCT00909779)
Timeframe: 0-12 months
| Intervention | Days (Mean) |
|---|---|
| Experimental: Arformoterol 15 Mcg Twice Daily | 155.0 |
| Placebo | 171.7 |
FEV1 was measured at Visit 1 (screening), pre- and post-albuterol administration for reversibility testing, pre-dose at baseline, months 3, 6, 9 and 12/EOS. The best FEV1 from at least 3 acceptable maneuvers was recorded. Study baseline was defined as the Visit 2 pre-dose value. If the Visit 2 pre-dose value was missing, the last FEV1 value obtained prior to first treatment was used for baseline. (NCT00909779)
Timeframe: Baseline and on treatments at months 3, 6, 9 and 12 (or early termination)
| Intervention | Liter (Mean) | ||||
|---|---|---|---|---|---|
| Month 3 (n=289,331) | Month 6 (n=248,300) | Month 9 (n=223,268) | Month 12 (n=206,253) | EOS (n=380,391) | |
| Experimental: Arformoterol 15 Mcg Twice Daily | 0.093 | 0.090 | 0.092 | 0.059 | 0.072 |
| Placebo Comparator: Placebo Twice Daily | 0.027 | 0.036 | 0.048 | 0.020 | 0.047 |
Forced Vital capacity: the volume of air that can forcibly be blown out after full inspiration. Best FVC was measured at Visit 1 (screening), pre-dose at baseline, months 3, 6, 9 and 12/EOS. The best FVC from at least 3 acceptable maneuvers was recorded. (NCT00909779)
Timeframe: Baseline and on treatment at months 3, 6, 9 and 12 (or early termination)
| Intervention | Liter (Least Squares Mean) | ||||
|---|---|---|---|---|---|
| Month 3 (n=289,331) | Month 6 (n=248,300) | Month 9 (n=223,268) | Month 12 (n=206,253) | EOS (n=380,391) | |
| Experimental: Arformoterol 15 Mcg Twice Daily | 0.139 | 0.120 | 0.139 | 0.088 | 0.102 |
| Placebo Comparator: Placebo Twice Daily | 0.039 | 0.056 | 0.049 | 0.040 | 0.056 |
"IC: the total amount of air that can be drawn into the lungs after normal expiration.~IC was measured pre- and post-albuterol administration at Visit 1 (screening), pre-dose at baseline, months 3, 6, 9 and 12/EOS. IC maneuvers were done in triplicate. The mean of all recorded IC values was used for each subject at each time point. Study baseline was defined as the Visit 2 pre-dose value. If the Visit 2 pre-dose value was missing, the last IC value obtained prior to first treatment dose was used for baseline." (NCT00909779)
Timeframe: Baseline and on treatment at months 3, 6, 9 and 12 (or early termination)
| Intervention | Liter (Least Squares Mean) | ||||
|---|---|---|---|---|---|
| Month 3 (n=284,320) | Month 6 (n=243,298) | Month 9 (n=218,258) | Month 12 (n=199,246) | EOS (n=374,384) | |
| Experimental: Arformoterol 15 Mcg Twice Daily | 0.054 | 0.067 | 0.096 | 0.035 | 0.058 |
| Placebo Comparator: Placebo Twice Daily | 0.030 | -0.011 | 0.046 | 0.004 | 0.031 |
Score on a scale 5-point Likert-type scale, ranging from 0 (none) to 4 (severe) for each symptom, total score is the sum of each symptom ranged from 0 to 16. Change from run-in. (NCT00929708)
Timeframe: Daily, during run-in and treatment
| Intervention | total score (Mean) |
|---|---|
| AZD3199 200 Mcg od | -0.96 |
| AZD3199 400 Mcg od | -0.91 |
| AZD3199 800 Mcg od | -1.21 |
| Formoterol 9 Mcg Bid | -0.56 |
| Placebo | -0.43 |
PK is only measured for AZD3199 (NCT00929708)
Timeframe: 0,15 min, 1, 4 and 24 hours post dose
| Intervention | nmol*h/L (Geometric Mean) |
|---|---|
| AZD3199 200 Mcg od | 4.83 |
| AZD3199 400 Mcg od | 8.69 |
| AZD3199 800 Mcg od | 14.82 |
change from baseline (NCT00929708)
Timeframe: 24h, 26h
| Intervention | Litre (Mean) |
|---|---|
| AZD3199 200 Mcg od | 0.11 |
| AZD3199 400 Mcg od | 0.12 |
| AZD3199 800 Mcg od | 0.11 |
| Formoterol 9 Mcg Bid | 0.03 |
| Placebo | 0.01 |
Change from baseline to treatment in score. The total scores vary between 0 (never/not limited at all) to 6 (almost all the time/totally limited). The data below represent the average of week 1,2,4 minus week 0. (NCT00929708)
Timeframe: Mean over week 0, mean over week 1, mean over week 2, and mean over week 4
| Intervention | score on scale (Mean) |
|---|---|
| AZD3199 200 Mcg od | -0.39 |
| AZD3199 400 Mcg od | -0.29 |
| AZD3199 800 Mcg od | -0.39 |
| Formoterol 9 Mcg Bid | -0.35 |
| Placebo | -0.10 |
change from baseline (NCT00929708)
Timeframe: 0,5 min, 15 min, 60 min, 2 h, 4 h
| Intervention | Litre (Mean) |
|---|---|
| AZD3199 200 Mcg od | 0.21 |
| AZD3199 400 Mcg od | 0.17 |
| AZD3199 800 Mcg od | 0.14 |
| Formoterol 9 Mcg Bid | 0.16 |
| Placebo | 0.03 |
Mean value of FEV1 pre and post salbutamol at visit 2 and visit 5 (NCT00929708)
Timeframe: Baseline (visit 2) and 26 h after the last morning dose (visit 5).
| Intervention | Litre (Mean) |
|---|---|
| AZD3199 200 Mcg od | 0.060 |
| AZD3199 400 Mcg od | 0.073 |
| AZD3199 800 Mcg od | 0.077 |
| Formoterol 9 Mcg Bid | 0.048 |
| Placebo | 0.018 |
PK is only measured for AZD3199 (NCT00929708)
Timeframe: 0,15 min, 1, 4 and 24 hours post dose
| Intervention | nmol/L (Geometric Mean) |
|---|---|
| AZD3199 200 Mcg od | 1.14 |
| AZD3199 400 Mcg od | 1.88 |
| AZD3199 800 Mcg od | 4.01 |
The total score is calculated using all questions including their weights and scores range from 0 (perfect health) to 100 (worst possible state) (NCT00929708)
Timeframe: At baseline (visit 2) and after 4 weeks of treatment (visit 5).
| Intervention | Score (Mean) |
|---|---|
| AZD3199 200 Mcg od | -5.10 |
| AZD3199 400 Mcg od | -8.17 |
| AZD3199 800 Mcg od | -5.01 |
| Formoterol 9 Mcg Bid | -5.16 |
| Placebo | -2.35 |
Change from run-in (NCT00929708)
Timeframe: During day (from rising from bed until going to bed) and night (from going to bed until rising from bed) at visit 1 to visit 5 (24h), up to 4 weeks.
| Intervention | Number of reliver inh. (Mean) |
|---|---|
| AZD3199 200 Mcg od | -0.96 |
| AZD3199 400 Mcg od | -1.23 |
| AZD3199 800 Mcg od | -1.15 |
| Formoterol 9 Mcg Bid | -0.66 |
| Placebo | -0.23 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT00931385)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.123 |
| Olo 5 mcg qd | -0.014 |
| Olo 10 mcg qd | 0.004 |
| Form 12 mcg Bid | 0.049 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT00931385)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.060 |
| Olo 5 mcg qd | 0.088 |
| Olo 10 mcg qd | 0.088 |
| Form 12 mcg Bid | 0.081 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres. (NCT00931385)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.092 |
| Olo 5 mcg qd | 0.037 |
| Olo 10 mcg qd | 0.046 |
| Form 12 mcg Bid | 0.065 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres. (NCT00931385)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the last am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.030 |
| Olo 5 mcg qd | 0.134 |
| Olo 10 mcg qd | 0.135 |
| Form 12 mcg Bid | 0.168 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00931385)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.086 |
| Olo 5 mcg qd | 0.139 |
| Olo 10 mcg qd | 0.142 |
| Form 12 mcg Bid | 0.117 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00931385)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.125 |
| Olo 5 mcg qd | 0.061 |
| Olo 10 mcg qd | 0.075 |
| Form 12 mcg Bid | 0.102 |
Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values at the randomisation visit. Peak FVC (0-3h) was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00931385)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.107 |
| Olo 5 mcg qd | 0.368 |
| Olo 10 mcg qd | 0.360 |
| Form 12 mcg Bid | 0.410 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00931385)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.164 |
| Olo 5 mcg qd | -0.016 |
| Olo 10 mcg qd | 0.008 |
| Form 12 mcg Bid | 0.088 |
Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values at the randomisation visit. Peak (0-3h) values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00931385)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.034 |
| Olo 5 mcg qd | 0.208 |
| Olo 10 mcg qd | 0.200 |
| Form 12 mcg Bid | 0.251 |
Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00931385)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.117 |
| Olo 5 mcg qd | 0.037 |
| Olo 10 mcg qd | 0.037 |
| Form 12 mcg Bid | 0.066 |
Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00931385)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.093 |
| Olo 5 mcg qd | 0.012 |
| Olo 10 mcg qd | 0.020 |
| Form 12 mcg Bid | 0.040 |
Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations). (NCT00931385)
Timeframe: 6 weeks
| Intervention | participants (Number) | |
|---|---|---|
| Heart rate increased | Tachycardia | |
| Form 12 mcg | 0 | 0 |
| Olo 10 mcg | 0 | 1 |
| Olo 5 mcg | 1 | 0 |
| Placebo | 0 | 0 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00932646)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.007 |
| Olo 5 mcg qd | 0.125 |
| Olo 10 mcg qd | 0.133 |
| Form 12 mcg Bid | 0.141 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00932646)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.012 |
| Olo 5 mcg qd | 0.109 |
| Olo 10 mcg qd | 0.115 |
| Form 12 mcg Bid | 0.093 |
Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations). (NCT00932646)
Timeframe: 6 weeks
| Intervention | participants (Number) | ||
|---|---|---|---|
| Bundle branch block right | ECG QT prolonged | Tachycardia | |
| Form 12 mcg | 0 | 0 | 1 |
| Olo 10 mcg | 1 | 1 | 0 |
| Olo 5 mcg | 0 | 0 | 0 |
| Placebo | 0 | 0 | 0 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT00932646)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.022 |
| Olo 5 mcg qd | 0.150 |
| Olo 10 mcg qd | 0.152 |
| Form 12 mcg Bid | 0.136 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT00932646)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.048 |
| Olo 5 mcg qd | 0.069 |
| Olo 10 mcg qd | 0.072 |
| Form 12 mcg Bid | 0.107 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres. (NCT00932646)
Timeframe: 1 h and 10 min prior to am dose on the first day of the treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.035 |
| Olo 5 mcg qd | 0.110 |
| Olo 10 mcg qd | 0.112 |
| Form 12 mcg Bid | 0.121 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres. (NCT00932646)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.004 |
| Olo 5 mcg qd | 0.190 |
| Olo 10 mcg qd | 0.202 |
| Form 12 mcg Bid | 0.217 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00932646)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.055 |
| Olo 5 mcg qd | 0.151 |
| Olo 10 mcg qd | 0.147 |
| Form 12 mcg Bid | 0.174 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00932646)
Timeframe: 1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.078 |
| Olo 5 mcg qd | 0.083 |
| Olo 10 mcg qd | 0.079 |
| Form 12 mcg Bid | 0.144 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00932646)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.076 |
| Olo 5 mcg qd | 0.268 |
| Olo 10 mcg qd | 0.273 |
| Form 12 mcg Bid | 0.293 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. (NCT00932646)
Timeframe: Baseline and 6 weeks
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | 0.138 |
| Olo 5 mcg qd | 0.436 |
| Olo 10 mcg qd | 0.440 |
| Form 12 mcg Bid | 0.475 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00932646)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
| Intervention | Liter (Least Squares Mean) |
|---|---|
| Placebo | -0.032 |
| Olo 5 mcg qd | 0.219 |
| Olo 10 mcg qd | 0.214 |
| Form 12 mcg Bid | 0.203 |
Participants' QOL were scored on a scale of decreasing QOL impairment from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) score from baseline were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.70 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.74 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -1.18 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.22 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.36 |
Change in the number of as-needed day-time inhalations of medication, defined as the difference in mean value of all available data obtained during treatment period and mean value in run-in period. (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Number of inhalations (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.30 |
Change in the number of as-needed night-time inhalations of medication, calculated as difference in mean value of all available data obtained during treatment period and mean value in run-in period. (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Number of inhalations (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.30 |
The mean percentage of days during treatment period participants used ≥ 3 inhalations of Symbicort® 160µg/4.5µg in a day (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort Turbuhaler | 28.25 |
The mean percentage of days during treatment period participants used ≥ 5 inhalations of Symbicort® 160µg/4.5µg in a day (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort Turbuhaler | 6.21 |
The mean percentage of days during treatment period participants used ≥ 9 inhalations of Symbicort® 160µg/4.5µg in a day (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Percentage of days (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.19 |
Total number of inhalations of Symbicort® 160µg/4.5µg per day during treatment period, defined as the sum of maintenance medication and as-needed medication during night and day time (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Number of inhalations (Mean) |
|---|---|
| Symbicort Turbuhaler | 2.51 |
Participants' QOL were scored on a scale of decreasing QOL impairment from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) symptom score from baseline were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.59 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.58 |
Participants' emotional functions were scored on a scale of decreasing impairment to emotional function from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) emotion function score were calculated as change from baseline (Week 0) to the treatment period (mean of the scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.77 |
Participants ' responses to environmental stimuli were scored on a scale of decreasing response to environmental stimuli from 1 to 7, in which 1 = maximum response. The change in overall mean AQLQ(S) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12) (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.67 |
Participants' QOL were scored on a scale of decreasing QOL impairment from 1 to 7, in which 1 = maximum impairment. The change in overall mean AQLQ(S) symptom score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | 0.77 |
Participants' levels of asthma control were scored on a 7-point Likert scale from 0 to 6, whereby 0 represents good control and 6 represents poor control of asthma. The regional mean change of overall ACQ(5) score were calculated as change from baseline (Week 0) to the average during the treatment period (mean of scores at Week 4, Week 8, Week 12). (NCT00939341)
Timeframe: Baseline and 12 weeks
| Intervention | Units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler | -0.58 |
(NCT00989833)
Timeframe: 6 weeks
| Intervention | Participants (Number) |
|---|---|
| Budesonide/Terbutaline | 13 |
| Terbutaline | 13 |
| Budesonide/Formoterol | 13 |
FEV1 (NCT00989833)
Timeframe: Baseline and 3 weeks
| Intervention | Percent change (Mean) |
|---|---|
| Budesonide/Terbutaline | -4.07 |
| Terbutaline | -1.19 |
| Budesonide/Formoterol | -3.81 |
FEV1 (NCT00989833)
Timeframe: Baseline and Visit 6
| Intervention | Percent change (Mean) |
|---|---|
| Budesonide/Terbutaline | -5.85 |
| Terbutaline | 0.61 |
| Budesonide/Formoterol | -5.24 |
Asthma symptoms during days with exercise (NCT00989833)
Timeframe: 6 weeks
| Intervention | Percent of exercise days (Mean) |
|---|---|
| Budesonide/Terbutaline | 51.1 |
| Terbutaline | 50.9 |
| Budesonide/Formoterol | 49.8 |
Change in cumulative Mannitol dose in mg in patients with a positive mannitol provocation test at baseline (PD15) (NCT00989833)
Timeframe: Baseline and 6 weeks
| Intervention | mg (Mean) |
|---|---|
| Budesonide/Terbutaline | 67.26 |
| Terbutaline | -6.15 |
| Budesonide/Formoterol | 151.87 |
Mean number of as needed inhalations taken before exercise (NCT00989833)
Timeframe: 6 weeks
| Intervention | number of inhalations per day (Mean) |
|---|---|
| Budesonide/Terbutaline | 0.6 |
| Terbutaline | 0.8 |
| Budesonide/Formoterol | 0.7 |
Change in overall ACQ5. ACQ5 measures asthma control and a lower values shows a better asthma control, a higher value is worse. A decrease in the ACQ5 shows an improvement during the treatment period. Range of ACQ5 is 0-5, with 0 as the best value and 5 as the worst value. Further information at www.qoltech.co.uk. (NCT00989833)
Timeframe: Baseline e and 6 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Budesonide/Terbutaline | -0.3 |
| Terbutaline | -0.2 |
| Budesonide/Formoterol | -0.4 |
(NCT00989833)
Timeframe: 6 weeks
| Intervention | ppb (Mean) |
|---|---|
| Budesonide/Terbutaline | 25.9 |
| Terbutaline | 35.5 |
| Budesonide/Formoterol | 24.4 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | 0.013 |
| Olo 2 mcg qd | 0.116 |
| Olo 5 mcg qd | 0.146 |
| Olo 10 mcg qd | 0.182 |
| Olo 20 mcg qd | 0.211 |
| Form 12 mcg Bid | 0.115 |
Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Number of patients (Number) | ||||
|---|---|---|---|---|---|
| No asthma symptoms | Mild asthma symptoms | Moderate asthma symptoms | Severe asthma symptoms | Very severe asthma symptoms | |
| Form 12 mcg Bid | 26 | 39 | 46 | 10 | 2 |
| Olo 10 mcg qd | 25 | 40 | 46 | 10 | 2 |
| Olo 2 mcg qd | 31 | 47 | 29 | 10 | 2 |
| Olo 20 mcg qd | 27 | 45 | 43 | 5 | 0 |
| Olo 5 mcg qd | 22 | 48 | 45 | 11 | 0 |
| Placebo | 27 | 32 | 49 | 14 | 0 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | 0.031 |
| Olo 2 mcg qd | 0.147 |
| Olo 5 mcg qd | 0.183 |
| Olo 10 mcg qd | 0.208 |
| Olo 20 mcg qd | 0.238 |
| Form 12 mcg Bid | 0.183 |
Percentage of asthma-symptom free days after the first 2 weeks of each treatment period was calculated as the number of symptom-free days divided by the number of days on treatment multiplied by 100. A symptom-free day was defined as a day in which no asthma symptoms were recorded, no rescue medication was recorded, activities during the day were not at all limited due to asthma, no shortness of breath during the day was recorded, no wheezing or coughing during the day and no night-time awakenings due to asthma were recorded. Assessed by patients at home using the AM2+ device. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Percentage of asthma symptom free days (Mean) |
|---|---|
| Placebo | 18.502 |
| Olo 2 mcg qd | 26.430 |
| Olo 5 mcg qd | 22.348 |
| Olo 10 mcg qd | 23.624 |
| Olo 20 mcg qd | 21.326 |
| Form 12 mcg Bid | 23.664 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | -0.039 |
| Olo 2 mcg qd | 0.124 |
| Olo 5 mcg qd | 0.173 |
| Olo 10 mcg qd | 0.194 |
| Olo 20 mcg qd | 0.211 |
| Form 12 mcg Bid | 0.145 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | -0.004 |
| Olo 2 mcg qd | 0.135 |
| Olo 5 mcg qd | 0.178 |
| Olo 10 mcg qd | 0.201 |
| Olo 20 mcg qd | 0.225 |
| Form 12 mcg Bid | 0.164 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h , 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | -0.047 |
| Olo 2 mcg qd | 0.056 |
| Olo 5 mcg qd | 0.109 |
| Olo 10 mcg qd | 0.094 |
| Olo 20 mcg qd | 0.122 |
| Form 12 mcg Bid | 0.055 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 min, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | -0.026 |
| Olo 2 mcg qd | 0.056 |
| Olo 5 mcg qd | 0.109 |
| Olo 10 mcg qd | 0.102 |
| Olo 20 mcg qd | 0.131 |
| Form 12 mcg Bid | 0.070 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | -0.005 |
| Olo 2 mcg qd | 0.055 |
| Olo 5 mcg qd | 0.109 |
| Olo 10 mcg qd | 0.110 |
| Olo 20 mcg qd | 0.139 |
| Form 12 mcg Bid | 0.085 |
Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Number of Puffs (Mean) |
|---|---|
| Placebo | 1.749 |
| Olo 2 mcg qd | 1.222 |
| Olo 5 mcg qd | 1.317 |
| Olo 10 mcg qd | 1.271 |
| Olo 20 mcg qd | 1.092 |
| Form 12 mcg Bid | 1.300 |
FEV1 p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | L (Mean) |
|---|---|
| Placebo | 2.378 |
| Olo 2 mcg qd | 2.428 |
| Olo 5 mcg qd | 2.460 |
| Olo 10 mcg qd | 2.467 |
| Olo 20 mcg qd | 2.495 |
| Form 12 mcg Bid | 2.457 |
PEF p.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Liter/min (Mean) |
|---|---|
| Placebo | 379.44 |
| Olo 2 mcg qd | 394.36 |
| Olo 5 mcg qd | 404.28 |
| Olo 10 mcg qd | 403.06 |
| Olo 20 mcg qd | 407.89 |
| Form 12 mcg Bid | 399.88 |
FEV1 a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | L (Mean) |
|---|---|
| Placebo | 2.309 |
| Olo 2 mcg qd | 2.402 |
| Olo 5 mcg qd | 2.438 |
| Olo 10 mcg qd | 2.445 |
| Olo 20 mcg qd | 2.479 |
| Form 12 mcg Bid | 2.403 |
PEF a.m. was measured by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Liter/min (Mean) |
|---|---|
| Placebo | 361.89 |
| Olo 2 mcg qd | 383.90 |
| Olo 5 mcg qd | 390.91 |
| Olo 10 mcg qd | 389.78 |
| Olo 20 mcg qd | 394.82 |
| Form 12 mcg Bid | 385.42 |
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1 h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min related to evening dose after 4 weeks
| Intervention | Liter/sec (Mean) |
|---|---|
| Placebo | -0.117 |
| Olo 2 mcg qd | 0.291 |
| Olo 5 mcg qd | 0.449 |
| Olo 10 mcg qd | 0.495 |
| Olo 20 mcg qd | 0.553 |
| Form 12 mcg Bid | 0.471 |
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -1h, -10 mins, 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter/sec (Mean) |
|---|---|
| Placebo | -0.038 |
| Olo 2 mcg qd | 0.336 |
| Olo 5 mcg qd | 0.489 |
| Olo 10 mcg qd | 0.534 |
| Olo 20 mcg qd | 0.623 |
| Form 12 mcg Bid | 0.532 |
Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Peak FEV1 within 24 hours post dose measured following the evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | 0.224 |
| Olo 2 mcg qd | 0.326 |
| Olo 5 mcg qd | 0.359 |
| Olo 10 mcg qd | 0.385 |
| Olo 20 mcg qd | 0.404 |
| Form 12 mcg Bid | 0.390 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Peak FVC within 24 hours post dose measured following the trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | 0.253 |
| Olo 2 mcg qd | 0.300 |
| Olo 5 mcg qd | 0.356 |
| Olo 10 mcg qd | 0.342 |
| Olo 20 mcg qd | 0.380 |
| Form 12 mcg Bid | 0.326 |
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Peak PEF within 24 hours post-dose measured following the evening trial drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 30 min, 60 min, 2 h, 3 h, 4 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter/sec (Mean) |
|---|---|
| Placebo | 0.664 |
| Olo 2 mcg qd | 0.966 |
| Olo 5 mcg qd | 1.093 |
| Olo 10 mcg qd | 1.130 |
| Olo 20 mcg qd | 1.198 |
| Form 12 mcg Bid | 1.168 |
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Means are adjusted for treatment, period, patient and study baseline. PEF AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres/seconds. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter/sec (Mean) |
|---|---|
| Placebo | 0.043 |
| Olo 2 mcg qd | 0.380 |
| Olo 5 mcg qd | 0.528 |
| Olo 10 mcg qd | 0.575 |
| Olo 20 mcg qd | 0.692 |
| Form 12 mcg Bid | 0.594 |
PEF daily variability was assessed by patients at home using the AM2+ device (overall means obtained during each period of randomised treatment excluding the data of the first 2 weeks will be compared). PEF daily variability is the absolute difference between the morning and the evening PEF value divided by the mean of these two values, expressed as a percent. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Percentage (Mean) |
|---|---|
| Placebo | 11.688 |
| Olo 2 mcg qd | 9.694 |
| Olo 5 mcg qd | 9.593 |
| Olo 10 mcg qd | 9.851 |
| Olo 20 mcg qd | 9.899 |
| Form 12 mcg Bid | 10.417 |
Effect on potassium evaluated 1 hour post-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale. (NCT01013753)
Timeframe: 4 weeks
| Intervention | mmol/L (Geometric Mean) |
|---|---|
| Placebo | 4.097 |
| Olo 2 mcg qd | 4.069 |
| Olo 5 mcg qd | 4.013 |
| Olo 10 mcg qd | 4.004 |
| Olo 20 mcg qd | 4.015 |
| Form 12 mcg Bid | 4.059 |
Effect on potassium evaluated 1 hour pre-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale. (NCT01013753)
Timeframe: 4 weeks
| Intervention | mmol/L (Geometric Mean) |
|---|---|
| Placebo | 4.067 |
| Olo 2 mcg qd | 4.051 |
| Olo 5 mcg qd | 4.051 |
| Olo 10 mcg qd | 4.061 |
| Olo 20 mcg qd | 4.057 |
| Form 12 mcg Bid | 4.080 |
Effect on potassium evaluated 3 hours post-dose. Analysis is based on the log of the potassium values. For the geometric means, the results were back-transformed to the original scale. (NCT01013753)
Timeframe: 4 weeks
| Intervention | mmol/L (Geometric Mean) |
|---|---|
| Placebo | 4.029 |
| Olo 2 mcg qd | 4.026 |
| Olo 5 mcg qd | 3.997 |
| Olo 10 mcg qd | 3.979 |
| Olo 20 mcg qd | 3.992 |
| Form 12 mcg Bid | 4.007 |
Control of asthma as assessed by the ACQ at the end of each 4-week treatment period.The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items. (NCT01013753)
Timeframe: 4 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | 1.882 |
| Olo 2 mcg qd | 1.561 |
| Olo 5 mcg qd | 1.589 |
| Olo 10 mcg qd | 1.556 |
| Olo 20 mcg qd | 1.488 |
| Form 12 mcg Bid | 1.536 |
Total score from the Standardised Asthma Quality of Life Questionnaire (AQLQ (s)) at the end of each 4 week treatment period. The AQLQ(s) contains 32 questions, each question has a 7 point scale from 1 (highest intensity) till 7 (no symptoms). Total score was defined as the sum of all items divided by the number of items. (NCT01013753)
Timeframe: 4 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | 5.174 |
| Olo 2 mcg qd | 5.463 |
| Olo 5 mcg qd | 5.383 |
| Olo 10 mcg qd | 5.437 |
| Olo 20 mcg qd | 5.491 |
| Form 12 mcg Bid | 5.489 |
Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter (Mean) |
|---|---|
| Placebo | -0.022 |
| Olo 2 mcg qd | 0.015 |
| Olo 5 mcg qd | 0.069 |
| Olo 10 mcg qd | 0.088 |
| Olo 20 mcg qd | 0.107 |
| Form 12 mcg Bid | 0.029 |
Response was defined as change from baseline. Study baseline PEF was defined as the mean of the available pre-dose PEF values at the randomisation visit. Trough values were defined as the mean of 2 FEV1 values performed at the planned timepoints 23h and 23h 50min related to evening trial-drug inhalation at the end of each 4 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01013753)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to evening dose after 4 weeks
| Intervention | Liter/sec (Mean) |
|---|---|
| Placebo | 0.031 |
| Olo 2 mcg qd | 0.295 |
| Olo 5 mcg qd | 0.499 |
| Olo 10 mcg qd | 0.515 |
| Olo 20 mcg qd | 0.655 |
| Form 12 mcg Bid | 0.478 |
Clinical relevant abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. (NCT01013753)
Timeframe: 4 weeks
| Intervention | Participants (Number) | |||||
|---|---|---|---|---|---|---|
| Atrioventricular block first degree | Blood creatine phosphokinase MB increased | Blood creatine phosphokinase increased | Blood pressure increased | Hypothyroidism | Hypertension | |
| Form 12 mcg Bid | 1 | 0 | 0 | 0 | 0 | 0 |
| Olo 10 mcg qd | 0 | 1 | 1 | 0 | 0 | 1 |
| Olo 2 mcg qd | 0 | 0 | 0 | 1 | 0 | 0 |
| Olo 20 mcg qd | 1 | 0 | 0 | 0 | 0 | 1 |
| Olo 5 mcg qd | 0 | 0 | 0 | 0 | 1 | 1 |
| Placebo | 0 | 0 | 0 | 0 | 0 | 0 |
Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Number of patients (Number) | ||||
|---|---|---|---|---|---|
| Did not wake up | Woke up once | Woke up 2-5 times | Woke up > 5 times | Was awake all night | |
| Form 12 mcg Bid | 59 | 29 | 33 | 2 | 0 |
| Olo 10 mcg qd | 56 | 34 | 30 | 1 | 2 |
| Olo 2 mcg qd | 60 | 36 | 17 | 5 | 1 |
| Olo 20 mcg qd | 63 | 34 | 20 | 2 | 1 |
| Olo 5 mcg qd | 58 | 34 | 30 | 2 | 2 |
| Placebo | 55 | 37 | 26 | 3 | 1 |
Assessed by patients at home using the AM2+ device after the first 2 weeks of each period of randomised treatment. (NCT01013753)
Timeframe: 2-4 weeks
| Intervention | Number of patients (Number) | ||||
|---|---|---|---|---|---|
| No asthma symptoms | Mild asthma symptoms | Moderate asthma symptoms | Severe asthma symptoms | Very severe asthma symptoms | |
| Form 12 mcg Bid | 24 | 37 | 49 | 12 | 1 |
| Olo 10 mcg qd | 23 | 37 | 52 | 10 | 1 |
| Olo 2 mcg qd | 26 | 46 | 37 | 10 | 0 |
| Olo 20 mcg qd | 21 | 38 | 54 | 6 | 1 |
| Olo 5 mcg qd | 29 | 29 | 51 | 12 | 5 |
| Placebo | 20 | 31 | 56 | 15 | 0 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | g/dl (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.00 |
| Arm 2 - Standard Treatment | 0.00 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mg/dl (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.02 |
| Arm 2 - Standard Treatment | -0.03 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | U/l (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.3 |
| Arm 2 - Standard Treatment | 4.9 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mg/dl (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.48 |
| Arm 2 - Standard Treatment | 0.07 |
The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group (NCT01047553)
Timeframe: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
| Intervention | Percentage of baseline (Geometric Mean) |
|---|---|
| Arm 1 - Formoterol | 101.62 |
| Arm 2 - Standard Treatment | 99.13 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mmHg (Mean) |
|---|---|
| Arm 1 - Formoterol | -2.1 |
| Arm 2 - Standard Treatment | -2.1 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mmHg (Mean) |
|---|---|
| Arm 1 - Formoterol | -2.7 |
| Arm 2 - Standard Treatment | -3.5 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | beats/minute (Mean) |
|---|---|
| Arm 1 - Formoterol | 1.5 |
| Arm 2 - Standard Treatment | -0.1 |
The change from Run-in period average to Treatment period average for each treatment group. (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
| Intervention | Times/Day (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.2 |
| Arm 2 - Standard Treatment | 0.0 |
The Total COPD Symptom score is the sum of the measures night-time awakening, breathlessness and cough, ranges from 0 to 12 with 12 being the most severe. The change from Run-in period average to Treatment period average for each treatment group. (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.5 |
| Arm 2 - Standard Treatment | -0.4 |
SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). A negative rate of decline shows decreasing SGRQ total score (or improved health) over time, while a positive value shows increasing score (or worsen health). The change from Run-in period average to Treatment period average for each treatment group (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Formoterol | -1.34 |
| Arm 2 - Standard Treatment | -0.57 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 52-week randomization treatment was presented here. (NCT01047553)
Timeframe: Daily during 52-week randomization treatment
| Intervention | number of exacerbations (Number) |
|---|---|
| Arm 1 - Formoterol | 27 |
| Arm 2 - Standard Treatment | 19 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
| Intervention | units on a scale (Median) |
|---|---|
| Arm 1 - Formoterol | 0.0 |
| Arm 2 - Standard Treatment | -0.1 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit)and daily during 52-week randomization treatment
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Arm 1 - Formoterol | 12.2 |
| Arm 2 - Standard Treatment | 7.3 |
The ratio of the average value of available data for mean from Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group (NCT01047553)
Timeframe: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
| Intervention | percentage of baseline (Geometric Mean) |
|---|---|
| Arm 1 - Formoterol | 101.46 |
| Arm 2 - Standard Treatment | 99.42 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Arm 1 - Formoterol | 9.6 |
| Arm 2 - Standard Treatment | 7.9 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | milisecond (Mean) |
|---|---|
| Arm 1 - Formoterol | -12.1 |
| Arm 2 - Standard Treatment | 131.7 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | milisecond (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.5 |
| Arm 2 - Standard Treatment | 1.7 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | milisecond (Mean) |
|---|---|
| Arm 1 - Formoterol | 2.1 |
| Arm 2 - Standard Treatment | 1.2 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | milisecond (Mean) |
|---|---|
| Arm 1 - Formoterol | -2.0 |
| Arm 2 - Standard Treatment | 2.6 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | beats/min (Mean) |
|---|---|
| Arm 1 - Formoterol | 2.0 |
| Arm 2 - Standard Treatment | 0.6 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.2 |
| Arm 2 - Standard Treatment | -0.1 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01047553)
Timeframe: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.2 |
| Arm 2 - Standard Treatment | -0.2 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | Platelet Count x10000/μl (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.17 |
| Arm 2 - Standard Treatment | -0.40 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | percentage of Monocyte (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.01 |
| Arm 2 - Standard Treatment | -0.03 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | percentage of Lymphocyte (Mean) |
|---|---|
| Arm 1 - Formoterol | -1.31 |
| Arm 2 - Standard Treatment | -0.43 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | leukocyte count/µL (Mean) |
|---|---|
| Arm 1 - Formoterol | -132.1 |
| Arm 2 - Standard Treatment | -289.5 |
Change from baseline (NCT01047553)
Timeframe: baseline and week 52
| Intervention | percentage of Eosinophil (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.49 |
| Arm 2 - Standard Treatment | 0.45 |
Change from Baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.009 |
| Arm 2 - Standard Treatment | 0.021 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | percentage of Basophil (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.05 |
| Arm 2 - Standard Treatment | 0.01 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | percentage of Neutrophil (Mean) |
|---|---|
| Arm 1 - Formoterol | 1.92 |
| Arm 2 - Standard Treatment | -0.28 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.29 |
| Arm 2 - Standard Treatment | -0.20 |
Mean change from Baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | erythrocytes counts x10000/μl (Mean) |
|---|---|
| Arm 1 - Formoterol | -6.25 |
| Arm 2 - Standard Treatment | -5.2 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | g/dl (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.05 |
| Arm 2 - Standard Treatment | -0.09 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.05 |
| Arm 2 - Standard Treatment | 0.02 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mEq/l (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.3 |
| Arm 2 - Standard Treatment | -0.2 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | mEq/L (Mean) |
|---|---|
| Arm 1 - Formoterol | -0.15 |
| Arm 2 - Standard Treatment | -0.07 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | U/l (Mean) |
|---|---|
| Arm 1 - Formoterol | 0.4 |
| Arm 2 - Standard Treatment | 2.6 |
Change from baseline (NCT01047553)
Timeframe: Baseline and week 52
| Intervention | U/l (Mean) |
|---|---|
| Arm 1 - Formoterol | 3.8 |
| Arm 2 - Standard Treatment | -4.4 |
Average FEV1 during 120 minutes post dose, change versus pre dose FEV1 (NCT01048333)
Timeframe: Pre dose and 120 minutes post dose
| Intervention | percentage change (Geometric Mean) |
|---|---|
| Formoterol | 1.096 |
| Salmeterol | 1.082 |
| Placebo | 1.014 |
FEV1(Forced Expiratory Volume in 1 second) measured by spirometry 5 minutes post dose, percentage change versus pre dose FEV1 (NCT01048333)
Timeframe: Pre-dose and 5 minutes post-dose
| Intervention | percentage change (Geometric Mean) |
|---|---|
| Formoterol | 1.072 |
| Salmeterol | 1.041 |
| Placebo | 1.007 |
Percentage of patients who has achieved at least 12 % increase in FEV1 at each time point between 5 to 120 minutes post dose, change versus pre dose FEV1 (NCT01048333)
Timeframe: Pre dose, 5, 10, 15, 20, 30, 40, 50, 60 and 120 minutes post dose
| Intervention | Percentage of Participants (Number) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 5 min | 10 min | 15 min | 20 min | 30 min | 40 min | 50 min | 60 min | 120 min | |
| Formoterol | 23.1 | 38.0 | 39.8 | 44.4 | 45.4 | 49.1 | 53.7 | 54.6 | 55.6 |
| Placebo | 6.4 | 7.3 | 9.2 | 10.1 | 13.8 | 15.6 | 16.5 | 18.3 | 20.2 |
| Salmeterol | 9.2 | 17.6 | 23.9 | 27.5 | 32.1 | 36.7 | 40.4 | 43.1 | 48.6 |
Average FEV1 during the first 15 minutes post dose, change versus pre dose FEV1 (NCT01048333)
Timeframe: Pre dose and 15 minutes post dose
| Intervention | percentage change (Geometric Mean) |
|---|---|
| Formoterol | 1.064 |
| Salmeterol | 1.041 |
| Placebo | 1.012 |
Number of participants with at least 1 AE. (NCT01048333)
Timeframe: At baseline and at each day of treatment
| Intervention | Participants (Number) |
|---|---|
| Formoterol | 6 |
| Salmeterol | 6 |
| Placebo | 2 |
(NCT01049360)
Timeframe: Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 400 μg / Formoterol 12 μg | 0.355 |
| Aclidinium 400 μg / Formoterol 6 μg | 0.348 |
| Aclidinium 400 μg | 0.260 |
| Formoterol 12 μg | 0.245 |
| Placebo | 0.073 |
(NCT01049360)
Timeframe: Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 400 μg / Formoterol 12 μg | 0.124 |
| Aclidinium 400 μg / Formoterol 6 μg | 0.129 |
| Aclidinium 400 μg | 0.080 |
| Formoterol 12 μg | 0.071 |
| Placebo | -0.008 |
(NCT01049360)
Timeframe: 0 to 12 hours post-dose on Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium 400 μg / Formoterol 12 μg | 0.187 |
| Aclidinium 400 μg / Formoterol 6 μg | 0.189 |
| Aclidinium 400 μg | 0.144 |
| Formoterol 12 μg | 0.114 |
| Placebo | -0.013 |
The Total COPD Symptom score is the sum of the measures night-time awakening, breathlessness and cough, ranges from 0 to 12 with 12 being the most severe. The change from Run-in period average to Treatment period average for each treatment group. (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.78 |
| Oxis Turbuhaler (Active Comparator) | -0.61 |
Total number of days with COPD exacerbation for each treatment group (NCT01069289)
Timeframe: Daily during 12-week randomization treatment
| Intervention | days (Number) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 653 |
| Oxis Turbuhaler (Active Comparator) | 1098 |
The change from Run-in period average to Treatment period average for each treatment group. (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | inhalations/day (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.51 |
| Oxis Turbuhaler (Active Comparator) | -0.26 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.34 |
| Oxis Turbuhaler (Active Comparator) | -0.23 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 102.2 |
| Oxis Turbuhaler (Active Comparator) | 100.9 |
The change from Run-in period average to Treatment period average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -4.37 |
| Oxis Turbuhaler (Active Comparator) | -2.90 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 113.9 |
| Oxis Turbuhaler (Active Comparator) | 111.2 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 110.1 |
| Oxis Turbuhaler (Active Comparator) | 108.7 |
There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.24 |
| Oxis Turbuhaler (Active Comparator) | -0.24 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter (L) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 0.0176 |
| Oxis Turbuhaler (Active Comparator) | -0.0324 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 2.55 |
| Oxis Turbuhaler (Active Comparator) | -5.13 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter (L) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 0.0244 |
| Oxis Turbuhaler (Active Comparator) | -0.0312 |
The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Liter/minute (L/min) (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 4.29 |
| Oxis Turbuhaler (Active Comparator) | -4.78 |
Scored 0 to 1 (0 = no awakening and 1 = awakening). The change from Run-in period average to Treatment period average for each treatment group (NCT01069289)
Timeframe: Daily during run-in period and daily during 12-week randomization treatment
| Intervention | Nights with symptoms (Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | -0.20 |
| Oxis Turbuhaler (Active Comparator) | -0.15 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 12-week randomization treatment (NCT01069289)
Timeframe: Daily during 12-week randomization treatment
| Intervention | event (Number) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 93 |
| Oxis Turbuhaler (Active Comparator) | 151 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group. (NCT01069289)
Timeframe: Daily during 12-week randomization treatment
| Intervention | percentage of participants (Number) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 11.9 |
| Oxis Turbuhaler (Active Comparator) | 16.9 |
The ratio, expressed as percentage, of the geometric mean of available data for Weeks 0, 4, 8 and 12 to the baseline for each treatment group (NCT01069289)
Timeframe: Before randomization, 0, 4, 8 and 12 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler (Experimental) | 104.6 |
| Oxis Turbuhaler (Active Comparator) | 101.5 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.7 |
| Arm 2 - COPD Standard Therapy | -1.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -4.5 |
| Arm 2 - COPD Standard Therapy | -7.5 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | beats/minute (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 3.6 |
| Arm 2 - COPD Standard Therapy | 3.4 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | *10000/μl (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.86 |
| Arm 2 - COPD Standard Therapy | 0.12 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | beats/minute (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 3.2 |
| Arm 2 - COPD Standard Therapy | 3.1 |
The change from run-in period and daily during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter(L) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.006 |
| Arm 2 - COPD Standard Therapy | 0.010 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -30.9 |
| Arm 2 - COPD Standard Therapy | -43.8 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.05 |
| Arm 2 - COPD Standard Therapy | 0.00 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Neutrophils (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 5.78 |
| Arm 2 - COPD Standard Therapy | 2.92 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | ms (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 3.6 |
| Arm 2 - COPD Standard Therapy | 2.4 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | /microliter(mcl) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 160.8 |
| Arm 2 - COPD Standard Therapy | -184.8 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.22 |
| Arm 2 - COPD Standard Therapy | -0.05 |
The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group. Ratio is being reported as a percentage in this Measure. (NCT01070784)
Timeframe: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 102.51 |
| Arm 2 - COPD Standard Therapy | 100.04 |
The change from run-in period and daily during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter(L) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.017 |
| Arm 2 - COPD Standard Therapy | 0.006 |
The change from Run-in period average to 52-week randomization Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter/minute(L/min) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 5.9 |
| Arm 2 - COPD Standard Therapy | 5.7 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during 52-week randomization treatment
| Intervention | event (Number) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 41 |
| Arm 2 - COPD Standard Therapy | 105 |
The change from run-in period and daily during 52-week randomization treatment (NCT01070784)
Timeframe: Daily during 52-week randomization treatment
| Intervention | innhalation/day (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.2 |
| Arm 2 - COPD Standard Therapy | 0.0 |
Mean change from Baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | *10000/μl (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -7.6 |
| Arm 2 - COPD Standard Therapy | -0.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Eosinophils (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.52 |
| Arm 2 - COPD Standard Therapy | 0.14 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Basophils (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.06 |
| Arm 2 - COPD Standard Therapy | -0.06 |
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group. (NCT01070784)
Timeframe: Daily during 52-week randomization treatment
| Intervention | Percentage of participants (Number) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 20.0 |
| Arm 2 - COPD Standard Therapy | 31.5 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.51 |
| Arm 2 - COPD Standard Therapy | -0.64 |
There are 5 alternatives (scored 0 to 4, 0= unaware of any difficulty and 4 =almost constant, present even when resting). The change from Run-in period average to Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.2 |
| Arm 2 - COPD Standard Therapy | -0.1 |
There are 5 alternatives (scored 0 to 4, 0= unaware of coughing, 4= never free of cough or need to cough). The change from Run-in period average to Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.2 |
| Arm 2 - COPD Standard Therapy | -0.2 |
There are 5 alternatives (scored 0 to 4, 0= no awakening and 4 =did not sleep at all). The change from Run-in period average to Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily during 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.0 |
| Arm 2 - COPD Standard Therapy | -0.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.02 |
| Arm 2 - COPD Standard Therapy | 0.01 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.03 |
| Arm 2 - COPD Standard Therapy | 0.04 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mmHg (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.8 |
| Arm 2 - COPD Standard Therapy | -1.3 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Monocytes (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.29 |
| Arm 2 - COPD Standard Therapy | -0.03 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mmHg (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.8 |
| Arm 2 - COPD Standard Therapy | -3.2 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | percentage of Lymphocytes (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -5.47 |
| Arm 2 - COPD Standard Therapy | -3.24 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mEq/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.8 |
| Arm 2 - COPD Standard Therapy | -0.6 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | g/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.01 |
| Arm 2 - COPD Standard Therapy | 0.02 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mEq/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -0.11 |
| Arm 2 - COPD Standard Therapy | -0.08 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | U/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.5 |
| Arm 2 - COPD Standard Therapy | 1.5 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.003 |
| Arm 2 - COPD Standard Therapy | -0.017 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | mg/dL (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.243 |
| Arm 2 - COPD Standard Therapy | 0.224 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | U/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 0.0 |
| Arm 2 - COPD Standard Therapy | 1.1 |
Change from baseline (NCT01070784)
Timeframe: Baseline and 52 week after
| Intervention | U/L (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 1.3 |
| Arm 2 - COPD Standard Therapy | 8.2 |
The change from run-in period and daily during 52-week randomization treatment average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | units on a scale (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | -2.03 |
| Arm 2 - COPD Standard Therapy | -0.42 |
The change from Run-in period average to 52-week randomization Treatment period average for each treatment group (NCT01070784)
Timeframe: Daily during run-in period and daily 52-week randomization treatment
| Intervention | Liter/minute(L/min) (Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 2.7 |
| Arm 2 - COPD Standard Therapy | 5.2 |
The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group. Ratio is being reported as a percentage in this Measure. (NCT01070784)
Timeframe: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
| Intervention | percentage of Baseline (Geometric Mean) |
|---|---|
| Arm 1 - Symbicort Turbuhaler | 104.25 |
| Arm 2 - COPD Standard Therapy | 98.43 |
"Mean difference between maximal percentage decrease in FEV1 after the exercise challenge compared to the run in period, budesonide/formoterol - budesonide, calculated as follows:~(max fall in FEV1(baseline) - maximal fall in FEV1(bud/form) - (max fall in FEV1(baseline) - maximal fall in FEV1(bud))" (NCT01070888)
Timeframe: 8 weeks
| Intervention | percentage of fall in FEV1 (Mean) |
|---|---|
| Budesonide First | -3.1 |
| Budesonide/Formoterol First | -19.4 |
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes (NCT01078623)
Timeframe: Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | -0.059 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.042 |
| Aclidinium 200 μg / Formoterol 6 μg | 0.067 |
| Aclidinium 200 μg | 0.072 |
| Formoterol 12 μg | 0.027 |
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose (NCT01078623)
Timeframe: 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | 0.052 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.335 |
| Aclidinium 200 μg / Formoterol 6 μg | 0.347 |
| Aclidinium 200 μg | 0.255 |
| Formoterol 12 μg | 0.255 |
FEV1 was measured via spirometry: 2 sets of tests prior to morning dose separated by 30 minutes, and then 1 set at 30 minutes, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose (NCT01078623)
Timeframe: 0 and 30 minutes and 1, 2, 3, 4, 6, 8, 10 and 12 hours post-morning dose at Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | -0.041 |
| Aclidinium 200 μg / Formoterol 12 μg | 0.180 |
| Aclidinium 200 μg / Formoterol 6 μg | 0.193 |
| Aclidinium 200 μg | 0.139 |
| Formoterol 12 μg | 0.100 |
Change from BaseLine in mean evening pre-dose daily peak flow rate on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters / Minute (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 35.0945 |
| GFF MDI 36/9.6 μg | 30.817 |
| GP MDI 36 μg | 18.487 |
| FF MDI 9.6 μg | 17.190 |
| FF MDI 7.2 μg | 14.805 |
| Foradil 12 μg | 17.789 |
Change from BaseLine in mean evening post-dose daily peak flow rate on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters / Minute (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 53.863 |
| GFF MDI 36/9.6 μg | 58.326 |
| GP MDI 36 μg | 36.637 |
| Spiriva 18 μg | 24.253 |
| FF MDI 9.6 μg | 41.395 |
| FF MDI 7.2 μg | 37.192 |
| Foradil 12 μg | 39.323 |
12 hour post-dose trough Forced Expiratory Volume in 1 second on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 1.405 |
| GFF MDI 36/9.6 μg | 1.441 |
| GP MDI 36 μg | 1.383 |
| Spiriva 18 μg | 1.398 |
| FF MDI 9.6 μg | 1.349 |
| FF MDI 7.2 μg | 1.378 |
| Foradil 12 μg | 1.358 |
Peak Change from Baseline Inspiratory Capacity on following 7-day dose administration (NCT01085045)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 0.409 |
| GFF MDI 36/9.6 μg | 0.438 |
| GP MDI 36 μg | 0.331 |
| Spiriva 18 μg | 0.314 |
| FF MDI 9.6 μg | 0.359 |
| FF MDI 7.2 μg | 0.376 |
| Foradil 12 μg | 0.393 |
Change from BaseLine in mean morning pre-dose daily peak flow rate on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters / Minute (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 30.263 |
| GFF MDI 36/9.6 μg | 28.152 |
| GP MDI 36 μg | 16.439 |
| Spiriva 18 μg | 11.817 |
| FF MDI 9.6 μg | 12.424 |
| FF MDI 7.2 μg | 10.211 |
| Foradil 12 μg | 13.426 |
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-12 (normalized) relative to baseline FEV1 following 7-day dose administration (NCT01085045)
Timeframe: "Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 10, 11.5, and 12 hours post-dose on Day 7"
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 1.537 |
| GFF MDI 36/9.6 μg | 1.529 |
| GP MDI 36 μg | 1.429 |
| Spiriva 18 μg | 1.434 |
| FF MDI 9.6 μg | 1.421 |
| FF MDI 7.2 μg | 1.413 |
| Foradil 12 μg | 1.437 |
Change from BaseLine in mean morning post-dose daily peak flow rate on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters / Minute (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 56.666 |
| GFF MDI 36/9.6 μg | 53.411 |
| GP MDI 36 μg | 33.652 |
| Spiriva 18 μg | 27.668 |
| FF MDI 9.6 μg | 41.287 |
| FF MDI 7.2 μg | 38.712 |
| Foradil 12 μg | 39.132 |
Change from Baseline in morning pre-dose FEV1 on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 0.193 |
| GFF MDI 36/9.6 μg | 0.170 |
| GP MDI 36 μg | 0.097 |
| Spiriva 18 μg | 0.097 |
| FF MDI 9.6 μg | 0.064 |
| FF MDI 7.2 μg | 0.073 |
| Foradil 12 μg | 0.101 |
Peak change from Baseline in Inspiratory Capacity (IC) on Day 1 (NCT01085045)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 0.495 |
| GFF MDI 36/9.6 μg | 0.411 |
| GP MDI 36 μg | 0.430 |
| Spiriva 18 μg | 0.347 |
| FF MDI 9.6 μg | 0.362 |
| FF MDI 7.2 μg | 0.352 |
| Foradil 12 μg | 0.374 |
Peak change from Baseline in FEV1 on Day 1 (NCT01085045)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 0.370 |
| GFF MDI 36/9.6 μg | 0.357 |
| GP MDI 36 μg | 0.289 |
| Spiriva 18 μg | 0.266 |
| FF MDI 9.6 μg | 0.308 |
| FF MDI 7.2 μg | 0.310 |
| Foradil 12 μg | 0.299 |
Time to Onset of Action where the improvement in FEV1 on Day 1 was >=10% (NCT01085045)
Timeframe: Day 1
| Intervention | Participants (Number) | ||||
|---|---|---|---|---|---|
| 15 Minutes | 30 Minutes | 60 Minutes | 120 Minutes | No onset | |
| FF MDI 7.2 μg | 34 | 12 | 4 | 2 | 9 |
| FF MDI 9.6 μg | 37 | 10 | 4 | 0 | 6 |
| Foradil 12 μg | 30 | 6 | 6 | 3 | 5 |
| GFF MDI 36/9.6 μg | 20 | 7 | 6 | 1 | 5 |
| GFF MDI 72/9.6 μg | 22 | 5 | 4 | 2 | 3 |
| GP MDI 36 μg | 14 | 10 | 3 | 4 | 6 |
| Spiriva 18 μg | 22 | 4 | 7 | 5 | 16 |
Time to Onset of Action where the improvement in FEV1 on Day 1 was >= 12% (NCT01085045)
Timeframe: Day 1
| Intervention | Percentage of Participants (Number) |
|---|---|
| GFF MDI 72/9.6 μg | 86.84 |
| GFF MDI 36/9.6 μg | 87.18 |
| GP MDI 36 μg | 73.68 |
| Spiriva 18 μg | 66.07 |
| FF MDI 9.6 μg | 84.48 |
| FF MDI 7.2 μg | 82.54 |
| Foradil 12 μg | 85.19 |
Peak change from Baseline (BL) in FEV1 on Day 7 (NCT01085045)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 72/9.6 μg | 0.438 |
| GFF MDI 36/9.6 μg | 0.440 |
| GP MDI 36 μg | 0.313 |
| Spiriva 18 μg | 0.298 |
| FF MDI 9.6 μg | 0.337 |
| FF MDI 7.2 μg | 0.330 |
| Foradil 12 μg | 0.356 |
(NCT01120093)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium Bromide 100 μg Bid | 0.044 |
| Aclidinium Bromide 200 μg Bid | 0.047 |
| Aclidinium Bromide 400 μg Bid | 0.086 |
| Formoterol 12 μg Bid | 0.141 |
| Placebo | -0.103 |
(NCT01120093)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium Bromide 100 μg Bid | 0.081 |
| Aclidinium Bromide 200 μg Bid | 0.089 |
| Aclidinium Bromide 400 μg Bid | 0.130 |
| Formoterol 12 μg Bid | 0.123 |
| Placebo | -0.025 |
(NCT01120093)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium Bromide 100 μg Bid | 0.088 |
| Aclidinium Bromide 200 μg Bid | 0.100 |
| Aclidinium Bromide 400 μg Bid | 0.133 |
| Formoterol 12 μg Bid | 0.163 |
| Placebo | -0.062 |
(NCT01120093)
Timeframe: Day 7
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium Bromide 100 μg Bid | 0.128 |
| Aclidinium Bromide 200 μg Bid | 0.151 |
| Aclidinium Bromide 400 μg Bid | 0.183 |
| Formoterol 12 μg Bid | 0.184 |
| Placebo | -0.026 |
Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was obtained from the full expiratory flow-volume-time curve. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. Twelve-hour serial FEV1 was calculated through an AUC determination and then divided by time, so that the final value is expressed in liters. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose
| Intervention | liters (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 1.546 |
| BUD 160/FM 4.5 | 1.594 |
| BUD 160/FM 9.0 | 1.603 |
| BUD 160 | 1.489 |
| BUD 160/ Foradil 12.0 | 1.603 |
Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. The FEV1 value at 12 hours after dosing was taken as the 12-hour measurement (720 minutes) from the serial spirometry. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: 12 hours after dosing
| Intervention | liters (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 1.641 |
| BUD 160/FM 4.5 | 1.692 |
| BUD 160/FM 9.0 | 1.731 |
| BUD 160 | 1.626 |
| BUD 160/ Foradil 12.0 | 1.709 |
Pulmonary function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 was measured at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes post administration of randomized study medication. The maximum FEV1 value was defined as the largest observed FEV1 value recorded during each 12-hour serial spirometry procedure. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: at 3, 9, 15, 60, 120, 180, 240, 360, 480, 600 and 720 minutes postdose
| Intervention | liters (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 1.833 |
| BUD 160/FM 4.5 | 1.889 |
| BUD 160/FM 9.0 | 1.884 |
| BUD 160 | 1.777 |
| BUD 160/ Foradil 12.0 | 1.892 |
The amount of formoterol excreted unchanged in urine over the 12-hour period after administration [Ae(0-12h)] was calculated from the concentration of formoterol in urine multiplied by the total volume of urine collected. Volume was determined from the weight of the collected urine times an assumed urine density of 1020 g/L. The data for six patients who did not have measurable formoterol in their urine on the Foradil 12 μg treatment day was excluded from the analysis. All other urine concentrations below the lower limit of quantification were set to zero. One subject was incorrectly administered BUD 160/ formoterol (FM) 9.0 rather than BUD 160/ Foradil 12.0 at Period 4. Hence this subject is included in the Efficacy Analysis Set, but not the Safety Analysis Set for BUD 160/ Foradil 12.0. (NCT01136655)
Timeframe: 0 to 12 hours
| Intervention | pmol (Least Squares Mean) |
|---|---|
| BUD 160/FM 2.25 | 192.0 |
| BUD 160/FM 4.5 | 366.3 |
| BUD 160/FM 9.0 | 740.6 |
| BUD 160/ Foradil 12.0 | 658.7 |
Blood glucose levels will be checked every 5 minutes during the 120 minute study session in order to maintain blood glucose levels in the normal and hypoglycemic range. Presented is the average of the collected values. (NCT01194479)
Timeframe: Up to 120 minutes
| Intervention | mg/dL (Mean) |
|---|---|
| Control: Placebo | 57.38 |
| Control: Formoterol | 58.39 |
| Type 1 Diabetics: Placebo | 53.21 |
| Type 1 Diabetics: Formoterol | 55.43 |
Norepinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages (NCT01194479)
Timeframe: up to 120 minutes
| Intervention | pg/mL (Mean) | ||
|---|---|---|---|
| Basal | Euglycemia | Hypoglycemia | |
| Control: Formoterol | 192 | 273 | 181 |
| Control: Placebo | 185 | 216 | 156 |
| Type 1 Diabetics: Formoterol | 133 | 211 | 190 |
| Type 1 Diabetics: Placebo | 180 | 226 | 241 |
Epinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages (NCT01194479)
Timeframe: up to 120 minutes
| Intervention | pg/mL (Mean) | ||
|---|---|---|---|
| Basal | Euglycemia | Hypoglycemia | |
| Control: Formoterol | 16 | 12 | 55 |
| Control: Placebo | 15 | 12 | 46 |
| Type 1 Diabetics: Formoterol | 17 | 13 | 19 |
| Type 1 Diabetics: Placebo | 18 | 21 | 44 |
Glucagon levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages. (NCT01194479)
Timeframe: up to 120 minutes
| Intervention | pg/mL (Mean) | ||
|---|---|---|---|
| Basal | Euglycemia | Hypoglycemia | |
| Control: Formoterol | 74 | 58 | 73 |
| Control: Placebo | 76 | 59 | 66 |
| Type 1 Diabetics: Formoterol | 56 | 54 | 46 |
| Type 1 Diabetics: Placebo | 53 | 55 | 43 |
The primary variable is the methacholine PC20 after inhalation of study medication; the PC20 is the concentration of methacholine that - despite protection by study medication - causes a 20% fall in FEV1 compared to the pre-methacholine (post-saline) level of the given study day. (NCT01256086)
Timeframe: 60 min after application of study medication
| Intervention | mg/ml (Geometric Mean) |
|---|---|
| 24 µg Formoterol Novolizer | 35.0 |
| 12µg Formoterol Novolizer | 20.9 |
| 24 µg Formoterol Aerolizer | 33.2 |
| 12µg Formoterol Aerolizer | 17.8 |
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. (NCT01258803)
Timeframe: Up to 12 hours postdose
| Intervention | Liters (Least Squares Mean) |
|---|---|
| MF/F MDI With Spacer | 0.115 |
| Placebo MDI With or Without Spacer | -0.009 |
Baseline was defined as the average of 2 predose measurements (taken 30 minutes and immediately before dosing). (NCT01258803)
Timeframe: Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose
| Intervention | Liters (Least Squares Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Baseline (n=79, 79, 79, 79) | 5 minutes postdose (n=79, 79, 79, 79) | 30 minutes postdose (n=79, 79, 79, 79) | 1 hour postdose (n=79, 79, 79, 79) | 2 hours postdose (n=79, 79, 79, 79) | 4 hours postdose (n=79, 79, 79, 79) | 8 hours postdose (n=79, 79, 79, 79) | 12 hours postdose (n=78, 79, 78, 79) | |
| F DPI | 1.570 | 0.105 | 0.117 | 0.136 | 0.135 | 0.118 | 0.087 | 0.059 |
| MF/F MDI With Spacer | 1.554 | 0.111 | 0.131 | 0.159 | 0.136 | 0.136 | 0.108 | 0.092 |
| MF/F MDI Without Spacer | 1.563 | 0.068 | 0.099 | 0.131 | 0.126 | 0.115 | 0.093 | 0.046 |
| Placebo MDI With or Without Spacer | 1.547 | -0.001 | 0.006 | 0.007 | 0.019 | 0.005 | -0.012 | -0.033 |
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. (NCT01258803)
Timeframe: Up to 12 hours postdose
| Intervention | Liters (Least Squares Mean) |
|---|---|
| F DPI | 0.097 |
| Placebo MDI With or Without Spacer | -0.009 |
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. (NCT01258803)
Timeframe: Up to 12 hours postdose
| Intervention | Liters (Least Squares Mean) |
|---|---|
| MF/F MDI Without Spacer | 0.093 |
| Placebo MDI With or Without Spacer | -0.009 |
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. (NCT01258803)
Timeframe: Up to 12 hours postdose
| Intervention | Liters (Least Squares Mean) |
|---|---|
| MF/F MDI With Spacer | 0.115 |
| MF/F MDI Without Spacer | 0.093 |
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. (NCT01258803)
Timeframe: Up to 12 hours postdose
| Intervention | Liters (Least Squares Mean) |
|---|---|
| MF/F MDI With Spacer | 0.115 |
| F DPI | 0.097 |
The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. (NCT01258803)
Timeframe: Up to 12 hours postdose
| Intervention | Liters (Least Squares Mean) |
|---|---|
| MF/F MDI Without Spacer | 0.093 |
| F DPI | 0.097 |
Baseline was defined as the average of 2 predose FVC measurements (taken 30 minutes and immediately before dosing). (NCT01258803)
Timeframe: Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose
| Intervention | Liters (Least Squares Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Baseline (n=79, 79, 79, 79) | 5 minutes postdose (n=79, 79, 79, 79) | 30 minutes postdose (n=79, 79, 79, 79) | 1 hour postdose (n=79, 79, 79, 79) | 2 hours postdose (n=79, 79, 79, 79) | 4 hours postdose (n=79, 79, 79, 79) | 8 hours postdose (n=79, 79, 79, 79) | 12 hours postdose (n=78, 79, 78, 79) | |
| F DPI | 1.928 | 0.032 | 0.017 | 0.022 | 0.047 | 0.008 | -0.013 | -0.014 |
| MF/F MDI With Spacer | 1.914 | 0.028 | 0.037 | 0.048 | 0.023 | 0.031 | -0.001 | -0.001 |
| MF/F MDI Without Spacer | 1.931 | 0.005 | 0.020 | 0.027 | 0.026 | 0.018 | 0.007 | -0.022 |
| Placebo MDI With or Without Spacer | 1.913 | 0.018 | 0.009 | -0.003 | 0.015 | -0.006 | -0.006 | -0.012 |
"Average Change in Asthma Control Score Per Participant Over 12 Months Using the Asthma Control Questionnaire (ACQ).~The ACQ has six questions regarding symptoms, rescue short-acting β-agonist use and one about FEV1 % predicted. A 7-point scale (0 = no impairment, 6 = maximum impairment) is used for each question and the ACQ score is the mean value of these questions - hence between 0 (totally controlled) and 6 (severely uncontrolled)." (NCT01290874)
Timeframe: from baseline to 12 months
| Intervention | units on a scale (Mean) |
|---|---|
| Tiotropium | -0.70 |
| Salmeterol or Formoterol | -0.66 |
"Average Change in Asthma Quality of Life Score Per Participant Over 12 Months Using the Asthma Quality of Life Questionnaire (AQLQ).~The AQLQ has 32 questions in four domains (symptoms, activity limitation, emotional function, and environmental stimuli) and measures the functional problems that are troublesome to individuals with asthma. Symptoms (11 items), Activity Limitation (12 items, 5 of which are individualized), Emotional Function (5 items), and Environmental Exposure (4 items); 7-point Likert scale (7 = not impaired at all - 1 = severely impaired); scores range 1-7, with higher scores indicating better quality of life." (NCT01290874)
Timeframe: from baseline to 12 months
| Intervention | units on a scale (Mean) |
|---|---|
| Tiotropium | 1.00 |
| Salmeterol or Formoterol | 1.02 |
"Average Change in Asthma Symptom Utility Score Per Participant Over 12 Months Using the Asthma Symptom Utility Index (ASUI).~The ASUI is an 11-item preference-based outcome measure used in clinical trials and cost-effectiveness studies for asthma and is designed to assess the frequency and severity of cough, wheeze, dyspnea, nighttime awakenings, and side effects, weighted according to patient preferences.~4-point Likert scale to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate and severe); scores range from 0 (worst possible symptoms) to 1 (no symptoms)." (NCT01290874)
Timeframe: from baseline to 12 months
| Intervention | units on a scale (Mean) |
|---|---|
| Tiotropium | 0.11 |
| Salmeterol or Formoterol | 0.10 |
Average change in lung function (FEV1) evaluated by spirometry per participant over 12 months (NCT01290874)
Timeframe: from baseline to 12 months
| Intervention | liters (Mean) |
|---|---|
| Tiotropium | -0.018 |
| Salmeterol or Formoterol | 0.003 |
Average Change in Rescue Medication Use Per Participant Over 12 Months. Monthly questionnaires will evaluate the amount of rescue medication subjects have used on average, measured in puffs per day. (NCT01290874)
Timeframe: from baseline to 12 months
| Intervention | units on a scale (Mean) |
|---|---|
| Tiotropium | -0.92 |
| Salmeterol or Formoterol | -0.97 |
We summarize the survival experience using mean number of exacerbations/person-year and compare it using the log-rank test comparing kaplan-meier survival curve. (NCT01290874)
Timeframe: evaluated monthly (on average) via questionnaire for 12 months
| Intervention | event per person-year (Mean) |
|---|---|
| Tiotropium | 0.37 |
| Salmeterol or Formoterol | 0.42 |
Trough FEV1 averaged over Day 7 and Day 14 (NCT01349803)
Timeframe: Day 7 to Day 14
| Intervention | Liters (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | 0.091 |
| GP MDI (PT001) | 0.126 |
| GFF MDI (PT003) | 0.251 |
| Foradil® Aerolizer® | 0.124 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: 24 hours
| Intervention | bpm (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | 0.56 |
| GP MDI (PT001) | -0.44 |
| GFF MDI (PT003) | 0.92 |
| Foradil® Aerolizer® | 0.31 |
The primary safety objective of this study was to compare the change in mean heart rate averaged over 24 hours post-dose, following twice daily dosing over 14 days with PT003 MDI, PT005 MDI, PT001 MDI or Foradil Aerolizer compared to baseline in patients with moderate to severe chronic obstructive pulmonary disease (COPD). (NCT01349803)
Timeframe: 14 days
| Intervention | bpm (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | -0.19 |
| GP MDI (PT001) | -1.84 |
| GFF MDI (PT003) | 0.40 |
| Foradil® Aerolizer® | -0.09 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | bpm (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | -4.71 | 0.75 |
| Foradil® Aerolizer® | 0.31 | -1.13 |
| GFF MDI (PT003) | -1.91 | -0.06 |
| GP MDI (PT001) | -1.88 | -2.21 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | bpm (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 0.00 | -1.22 |
| Foradil® Aerolizer® | -0.17 | -0.54 |
| GFF MDI (PT003) | 0.16 | -0.40 |
| GP MDI (PT001) | -0.52 | -2.00 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | bpm (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 3.05 | 0.04 |
| Foradil® Aerolizer® | 0.70 | 1.05 |
| GFF MDI (PT003) | 2.95 | 0.11 |
| GP MDI (PT001) | -0.54 | -0.88 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Ventricular events / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 1.31 | 3.09 |
| Foradil® Aerolizer® | 0.45 | -0.54 |
| GFF MDI (PT003) | 1.59 | -0.10 |
| GP MDI (PT001) | 0.56 | 0.62 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Bradycardia episodes / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | -0.04 | -0.02 |
| Foradil® Aerolizer® | 0.03 | 0.13 |
| GFF MDI (PT003) | 0.11 | 0.27 |
| GP MDI (PT001) | -0.02 | 0.40 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Supraventricular events / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 7.72 | 3.61 |
| Foradil® Aerolizer® | 15.36 | 5.81 |
| GFF MDI (PT003) | -4.55 | 3.61 |
| GP MDI (PT001) | 0.74 | -9.29 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Supraventricular couplets / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 0.03 | 0.01 |
| Foradil® Aerolizer® | 0.04 | -0.02 |
| GFF MDI (PT003) | 0.05 | 0.00 |
| GP MDI (PT001) | 0.01 | 0.00 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Supraventricular runs / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 0.00 | 0.01 |
| Foradil® Aerolizer® | 0.01 | 0.01 |
| GFF MDI (PT003) | 0.01 | 0.00 |
| GP MDI (PT001) | 0.02 | 0.02 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Tachycardia episodes / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | -0.16 | -0.23 |
| Foradil® Aerolizer® | -0.09 | -0.01 |
| GFF MDI (PT003) | -0.02 | 0.22 |
| GP MDI (PT001) | -0.24 | -0.34 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Ventricular couplets / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 0.09 | 0.02 |
| Foradil® Aerolizer® | 0.00 | -0.01 |
| GFF MDI (PT003) | 0.00 | -0.03 |
| GP MDI (PT001) | 0.00 | 0.00 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | Ventricular runs / hour (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | -0.003 | -0.004 |
| Foradil® Aerolizer® | -0.003 | -0.004 |
| GFF MDI (PT003) | 0.001 | 0.001 |
| GP MDI (PT001) | -0.001 | 0.001 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, Day 7, and Day 14
| Intervention | msec (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Day 1: Post-dose 30 minutes | Day 1: Post-dose 2 hours | Day 1: Post-dose 24 hours | Day 7: Pre-dose | Day 14: Pre-dose | Day 14: Post-dose 30 minutes | Day 14: Post-dose 2 hours | Day 14: Post-dose 24 hours | |
| FF MDI (PT005) | 1.53 | 1.75 | -0.09 | -1.80 | -0.59 | 1.21 | 0.44 | -1.32 |
| Foradil® Aerolizer® | 3.71 | 5.25 | 0.36 | 3.85 | 1.53 | 1.20 | 3.98 | 1.44 |
| GFF MDI (PT003) | 3.27 | 1.62 | -1.43 | 1.06 | -0.42 | 2.23 | 5.01 | -1.93 |
| GP MDI (PT001) | 4.67 | 3.57 | 1.23 | 1.40 | 1.79 | 4.10 | 6.02 | -0.05 |
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation). (NCT01349803)
Timeframe: Baseline, Day 1, and Day 14
| Intervention | bpm (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| FF MDI (PT005) | 0.05 | -0.79 |
| Foradil® Aerolizer® | 0.45 | 0.88 |
| GFF MDI (PT003) | 0.50 | -0.21 |
| GP MDI (PT001) | -0.03 | -1.92 |
FEV1 (NCT01391559)
Timeframe: 2 hours
| Intervention | mL (Mean) |
|---|---|
| Arformoterol | 84 |
| Salmeterol | 52 |
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to first week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 13.405 |
| Spiriva | -0.182 |
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value (NCT01397890)
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.050 |
| Spiriva | 1.006 |
Change in the number of inhalations of reliever medication during night from run-in period to the whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.241 |
| Spiriva | -0.010 |
Change in the number of inhalations of reliever medication during night from run-in period to the last week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.174 |
| Spiriva | 0.062 |
Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.113 |
| Spiriva | 0.011 |
Change in the number of inhalations of reliever medication during day from run-in period to the whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period of 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.685 |
| Spiriva | -0.134 |
Change in the number of inhalations of reliever medication during day from run-in period to the last week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment, up to 12 weeks
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.750 |
| Spiriva | -0.082 |
Change in the number of inhalations of reliever medication during day from run-in period to the first week on treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.457 |
| Spiriva | -0.082 |
Change in pre-dose morning PEF from run-in period to whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period of 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 12.271 |
| Spiriva | -5.198 |
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment, up to 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 15.753 |
| Spiriva | -4.550 |
Ratio of pre-dose IC (Inspiratory Capacity) in treatment period to baseline value (NCT01397890)
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.042 |
| Spiriva | 1.022 |
Ratio of pre-dose FVC (Forced Vital Capacity) in treatment period to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.032 |
| Spiriva | 1.013 |
Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period of 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 15.880 |
| Spiriva | -2.591 |
Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment, up to 12 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 23.379 |
| Spiriva | -3.049 |
Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 17.412 |
| Spiriva | 0.220 |
Ratio of post-dose IC at 60 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.154 |
| Spiriva | 1.087 |
Ratio of post-dose FVC at 60 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.116 |
| Spiriva | 1.059 |
Ratio of post-dose FVC at 5 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.096 |
| Spiriva | 1.044 |
Ratio of post-dose FEV1 at 60 minutes to baseline value (NCT01397890)
Timeframe: Baseline (measured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.164 |
| Spiriva | 1.072 |
Change in breathing symptom score (from 0:none to 4:severe) from run-in period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.372 |
| Spiriva | -0.110 |
Change in Cough symptom score (from 0:none to 4:severe) from run-in period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.311 |
| Spiriva | -0.169 |
Change in Sputum symptom score (from 0:none to 4:severe) from run-in period (NCT01397890)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period of 12 weeks
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | -0.216 |
| Spiriva | -0.094 |
Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms (NCT01397890)
Timeframe: Whole treatment period of 12 weeks
| Intervention | exacerbations/participant/12 weeks (Least Squares Mean) |
|---|---|
| Symbicort+Spiriva | 0.182 |
| Spiriva | 0.307 |
Ratio of post-dose FEV1 at 5 minutes to baseline value (NCT01397890)
Timeframe: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort+Spiriva | 1.128 |
| Spiriva | 1.045 |
Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 23.135 |
| Ipratropium + Theophylline SR | -2.038 |
Ratio of post-dose FEV1 at 5 minutes to baseline value (NCT01415518)
Timeframe: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.179 |
| Ipratropium + Theophylline SR | 1.106 |
Ratio of post-dose FEV1 at 60 minutes to baseline value (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.219 |
| Ipratropium + Theophylline SR | 1.142 |
Ratio of post-dose FVC at 5 minutes to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.170 |
| Ipratropium + Theophylline SR | 1.120 |
Ratio of post-dose FVC at 60 minutes to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.192 |
| Ipratropium + Theophylline SR | 1.148 |
Ratio of post-dose IC at 60 minutes to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.163 |
| Ipratropium + Theophylline SR | 1.120 |
Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured at 5 minutes after inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 25.993 |
| Ipratropium + Theophylline SR | 1.670 |
Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 36.612 |
| Ipratropium + Theophylline SR | 5.100 |
Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms (NCT01415518)
Timeframe: Whole treatment period (12 weeks)
| Intervention | exacerbations/12 weeks (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 0.069 |
| Ipratropium + Theophylline SR | 0.121 |
Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period (12 weeks)
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 26.507 |
| Ipratropium + Theophylline SR | -0.662 |
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value (NCT01415518)
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.079 |
| Ipratropium + Theophylline SR | 1.009 |
Ratio of pre-dose FVC (Forced Vital Capacity) to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.072 |
| Ipratropium + Theophylline SR | 1.030 |
Ratio of pre-dose IC (Inspiratory Capacity) to baseline (NCT01415518)
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)
| Intervention | Ratio (Geometric Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 1.068 |
| Ipratropium + Theophylline SR | 1.032 |
Change in pre-dose morning PEF from run-in period to whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period (12 weeks)
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 21.021 |
| Ipratropium + Theophylline SR | -2.023 |
Change in pre-dose morning PEF from run-in period to first week of treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured before inhalation of study drug in the first week of treatment
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | 24.393 |
| Ipratropium + Theophylline SR | 3.257 |
Change in the number of inhalations of reliever medication during day from run-in to the first week on treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.440 |
| Ipratropium + Theophylline SR | -0.097 |
Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Intervention | Score from 0 to 4 (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.507 |
| Ipratropium + Theophylline SR | -0.229 |
Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Intervention | Score from 0 to 4 (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.332 |
| Ipratropium + Theophylline SR | -0.124 |
Change in the number of inhalations of reliever medication during day from run-in to the last week on treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.398 |
| Ipratropium + Theophylline SR | -0.101 |
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period (12 weeks)
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.404 |
| Ipratropium + Theophylline SR | -0.061 |
change in the number of inhalations of reliever medication during day from run-in to the first week on treatment (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.124 |
| Ipratropium + Theophylline SR | -0.002 |
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the last week on treatment
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.078 |
| Ipratropium + Theophylline SR | -0.023 |
Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)
| Intervention | Score from 0 to 4 (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.441 |
| Ipratropium + Theophylline SR | -0.248 |
Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period (NCT01415518)
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the whole treatment period (12 weeks)
| Intervention | times/day (Least Squares Mean) |
|---|---|
| Symbicort Turbuhaler + Ipratropium + Theophylline SR | -0.086 |
| Ipratropium + Theophylline SR | 0.020 |
(NCT01437397)
Timeframe: Week 24 of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium/Formoterol 400/12 μg | 0.247 |
| Aclidinium/Formoterol 400/6 μg | 0.226 |
| Aclidinium 400 μg | 0.139 |
| Formoterol 12 μg | 0.165 |
| Placebo | -0.037 |
"The TDI measures the change from baseline in severity of breathlessness in symptomatic patients. The TDI contains a rating for 3 categories (functional impairment, magnitude of task, magnitude of effort).TDI scale ranges from -3 (major deterioration) to +3 (major improvement) including a 0 score to indicate no change. The 3 categories are added to obtain a focal score ranging from -9 (including 0) to +9." (NCT01437397)
Timeframe: Week 24 of treatment
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Aclidinium/Formoterol 400/12 μg | 2.017 |
| Aclidinium/Formoterol 400/6 μg | 1.977 |
| Aclidinium 400 μg | 1.558 |
| Formoterol 12 μg | 1.522 |
| Placebo | 0.582 |
St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 2 parts with 3 dimension scores (a symptom score and an activity and impacts score). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status). (NCT01437397)
Timeframe: Week 24 of treatment
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Aclidinium/Formoterol 400/12 μg | -6.568 |
| Aclidinium/Formoterol 400/6 μg | -5.942 |
| Aclidinium 400 μg | -6.438 |
| Formoterol 12 μg | -4.701 |
| Placebo | -2.215 |
(NCT01437397)
Timeframe: Week 24 of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium/Formoterol 400/12 μg | 0.095 |
| Aclidinium/Formoterol 400/6 μg | 0.076 |
| Aclidinium 400 μg | 0.066 |
| Formoterol 12 μg | 0.050 |
| Placebo | -0.035 |
Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline; Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline; Pulse rate ≥ 110 bpm and increase ≥ 15% from baseline or ≤ 50 bpm and decrease ≥15% from baseline (NCT01437540)
Timeframe: Up to study Week 56 ± 3 days
| Intervention | Percentage of patients (Number) | |||||
|---|---|---|---|---|---|---|
| Systolic BP ≥180 mmHg and increase ≥20 mmHg | Systolic BP ≤90 mmHg and decrease ≥20 mmHg | Diastolic BP ≥105 mmHg and increase ≥15 mmHg | Diastolic BP ≤50 mmHg and decrease ≥15 mmHg | Pulse rate ≥ 110 bpm and increase ≥ 15% | Pulse rate ≤ 50 bpm and decrease ≥15% | |
| Aclidinium/Formoterol 400 μg/12 μg | 0.3 | 1.5 | 0 | 0.3 | 0.8 | 0 |
| Formoterol 12 μg | 0.5 | 1.0 | 0.5 | 1.0 | 0.5 | 0 |
Potentially clinically significant changes were defined as listed in the table below for QT interval, QTcB, QTcF, QRS interval, PR interval and heart rate (HR) (NCT01437540)
Timeframe: Up to study Week 56 ± 3 days
| Intervention | Percentage of patients (Number) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| QT interval change from baseline >30 msec | QT interval >480 msec | QTcB change from baseline >30 msec | QTcB value >480 msec | QTcF change from baseline >30 msec | QTcF value >480 msec | QRS interval ≥100 msec and increase ≥25% from base | PR interval ≥200 msec and increase ≥25% from base | HR ≥110 bpm and decrease ≥15% from baseline | HR ≤50 bpm and decrease ≥15% from baseline | |
| Aclidinium/Formoterol 400 μg/12 μg | 42.0 | 3.9 | 31.1 | 3.1 | 21.5 | 1.5 | 2.0 | 2.8 | 2.6 | 4.6 |
| Formoterol 12 μg | 44.7 | 2.0 | 30.3 | 4.5 | 22.7 | 1.5 | 1.0 | 1.0 | 1.0 | 4.0 |
TEAEs were coded Version 16.0 of the Medical Dictionary for Regulatory Activities (MedDRA) (NCT01437540)
Timeframe: Up to study Week 56 ± 3 days
| Intervention | Percentage of participants (Number) |
|---|---|
| Aclidinium/Formoterol 400 μg/12 μg | 71.4 |
| Formoterol 12 μg | 65.7 |
"<0.85 x lower limit of normal (LLN) or > 1.15 upper limit of normal (ULN) for hemoglobin, hematocrit, red blood cell, platelet, white blood cell, neutrophil and lymphocyte counts >1.15 × ULN for eosinophil, basophil and monocyte counts~>1.15 x ULN for aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine kinase, lactate dehydrogenase, blood urea nitrogen, creatinine, uric acid, total cholesterol, triglycerides <0.85 x LLN or >1.15 ULN for fasting glucose, calcium, phosphorus, total protein and albumin <0.95 x LLN or >1.05 x ULN for sodium, potassium and chloride~Urinary blood, ketones or pH <0.85 x LLN or > 1.15 ULN" (NCT01437540)
Timeframe: Up to study Week 52
| Intervention | Percentage of participants (Number) |
|---|---|
| Aclidinium/Formoterol 400 μg/12 μg | 63.9 |
| Formoterol 12 μg | 62.1 |
(NCT01462942)
Timeframe: Baseline and Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | -0.061 |
| Aclidinium/Formoterol 400/12 μg | 0.083 |
| Aclidinium/Formoterol 400/6 μg | 0.050 |
| Aclidinium 400 μg | 0.056 |
| Formoterol 12 μg | -0.002 |
(NCT01462942)
Timeframe: Baseline and Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | -0.030 |
| Aclidinium/Formoterol 400/12 μg | 0.269 |
| Aclidinium/Formoterol 400/6 μg | 0.213 |
| Aclidinium 400 μg | 0.144 |
| Formoterol 12 μg | 0.129 |
SGRQ is a standardised, self-administered tool for measuring impaired health and perceived well-being in respiratory diseases; a validated electronic version of the questionnaire in the relevant validated languages was used in this study The questionnaire contains 50 items divided into three dimensions (Symptoms, Activity and Impact) Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100: zero (0) score indicating no impairment of quality of life The total SGRQ score ranging from 0 to 100 is a summary score utilising responses to all items calculated using weights attached to each item of the questionnaire Higher scores indicate poorer health and change of 4 units in the SGRQ has been determined to be the threshold for a clinically relevant change in health status (NCT01462942)
Timeframe: Baseline and Week 24
| Intervention | Score on a scale (Least Squares Mean) |
|---|---|
| Placebo | -6.511 |
| Aclidinium/Formoterol 400/12 μg | -7.164 |
| Aclidinium/Formoterol 400/6 μg | -8.339 |
| Aclidinium 400 μg | -5.801 |
| Formoterol 12 μg | -5.579 |
Evaluation of dyspnea was performed by an independent interviewer experienced in taking a respiratory history The TDI includes three categories: functional impairment which determines the impact of breathlessness on the ability to perform activities, magnitude of task which determines the type of task that caused breathlessness and magnitude of effort which establishes the level of effort needed to evoke breathlessness Each category ranges from minus three (-3; major deterioration) to plus three (+3; major improvement) including a zero (0) score to indicate 'no change' The three categories are totalled to obtain a focal score (total score) ranging from minus nine (-9), including zero (0), to plus nine (+9) Provision is made for circumstances when dyspnoea could not be rated - if reduction of activities, effort or functional impairment was caused by reasons other than respiratory A change of 1 unit in TDI is used as the criterion for a minimal meaningful improvement (NCT01462942)
Timeframe: Baseline and Week 24
| Intervention | Score on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.215 |
| Aclidinium/Formoterol 400/12 μg | 2.508 |
| Aclidinium/Formoterol 400/6 μg | 2.377 |
| Aclidinium 400 μg | 2.112 |
| Formoterol 12 μg | 2.062 |
The primary safety outcome was the time-to-first SAO (a composite endpoint of adjudicated asthma-related hospitalizations, adjudicated asthma-related intubations, and adjudicated asthma-related deaths). To accomplish this, the number of participants experiencing a first SAO was collected for 26 weeks following initiation of study treatment (or 7 days after the last treatment dose, whichever occurred later). Data generated by this methodology were used to compute a hazard ratio (HR) and 95% confidence interval (CI), modeling the likelihood of a first SAO occurring at any given time in the MF/F arm relative to the MF arm. Although data were sufficient to generate a HR and 95% CI, time-to-first SAO in the overall population could not be accurately reported due to insufficient SAO occurrence. Therefore, the number of first SAO in either arm is reported as a descriptive measure. For each participant, first SAO denotes first event per participant. (NCT01471340)
Timeframe: 26 weeks, or 7 days after the last treatment dose, whichever occurred later
| Intervention | Serious asthma outcomes (Number) |
|---|---|
| MF/F MDI BID | 39 |
| MF MDI BID | 32 |
The key secondary efficacy outcome was time-to-first protocol-defined asthma exacerbation (SAEX). The SAEX were deteriorations of asthma requiring: use of systemic corticosteroids (tablets, suspension, or injection) for >= 3 consecutive days, in-patient hospitalization >= 24 hours, or an emergency department (ED) visit < 24 hours that required systemic corticosteroids in the MF/F MDI BID arm versus the MF MDI BID arm. The number of first SAEX occurred from initiation of study treatment to 7 days after the last treatment (modified intention-to-treat). This outcome was measured as the HR and 95% CI for the number of first SAEX in the MF/F MDI BID arm versus the number of first SAEX in the MF MDI BID arm. Given insufficient data for SAEX events, it was not informative to report the time-to-first SAEX in the overall population. Therefore, the number of first SAEXs in either arm is reported as a descriptive measure. For each participant, first SAEX denotes first event per participant. (NCT01471340)
Timeframe: 26 weeks, plus 7 days after the last treatment
| Intervention | Asthma exacerbations (Number) |
|---|---|
| MF/F MDI BID | 708 |
| MF MDI BID | 779 |
To further examine the primary safety outcome, each adjudicated component of the SAO composite endpoint (asthma-related hospitalization, asthma-related intubation and asthma-related death), was tabulated for descriptive purposes only to show the relative contribution of each component to the SAO composite. Hospitalizations were defined as an in-patient stay of >= 24 hour in a hospital, emergency department or equivalent healthcare facility. Intubation was defined as endotracheal intubation only. (NCT01471340)
Timeframe: 26 weeks, or 7 days after the last treatment dose, whichever occurred later
| Intervention | SAO components (Number) | |||
|---|---|---|---|---|
| First SAO | Asthma-related hospitalizations | Asthma-related intubations | Asthma-related deaths | |
| MF MDI BID | 32 | 32 | 0 | 0 |
| MF/F MDI BID | 39 | 39 | 0 | 0 |
Number of puffs of rescue medication (albuterol pMDI) used per day (NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Mean Puffs per Day (Mean) | |
|---|---|---|
| Baseline | Treatment Phase | |
| Matching Placebo | 2.52 | 2.35 |
| Perforomist Inhalation Solution | 2.55 | 1.92 |
(NCT01488019)
Timeframe: On treatment at months 3, 6, 9 and 12
| Intervention | Litres (Mean) | |||
|---|---|---|---|---|
| Change from Baseline IC: Month 3 | Change from Baseline IC: Month 6 | Change from Baseline IC: Month 9 | Change from Baseline IC: Month 12 | |
| Matching Placebo | -0.0119 | -0.0106 | -0.0118 | -0.0105 |
| Perforomist Inhalation Solution | 0.0287 | 0.0440 | 0.1584 | 0.0477 |
(NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| 0 | 1 | 2 | >=3 | |
| Matching Placebo | 437 | 75 | 16 | 2 |
| Perforomist Inhalation Solution | 447 | 78 | 15 | 1 |
(NCT01488019)
Timeframe: On treatment at months 3, 6, 9 and 12
| Intervention | Litres (Mean) | |||
|---|---|---|---|---|
| Change from Baseline FVC: Month 3 | Change from Baseline FVC: Month 6 | Change from Baseline FVC: Month 9 | Change from Baseline FVC: Month 12 | |
| Matching Placebo | 0.0062 | -0.0241 | -0.0254 | -0.0581 |
| Perforomist Inhalation Solution | 0.1051 | 0.1006 | 0.1009 | 0.0645 |
(NCT01488019)
Timeframe: On treatment at months 3, 6, 9 and 12
| Intervention | Litres (Least Squares Mean) | |||
|---|---|---|---|---|
| Change from Baseline FEV1: Month 3 | Change from Baseline FEV1: Month 6 | Change from Baseline FEV1: Month 9 | Change from Baseline FEV1: Month 12 | |
| Matching Placebo | 0.016 | 0.017 | 0.029 | 0.000 |
| Perforomist Inhalation Solution | 0.058 | 0.057 | 0.050 | 0.030 |
(NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Perforomist Inhalation Solution | 3 |
| Matching Placebo | 10 |
COPD exacerbations were defined as events in the natural course of disease characterized by an increase from baseline in two of the following symptoms: dyspnea, cough, and sputum production that was beyond normal day-to-day variations, was acute in onset, that persisted for at least two consecutive days, and that warranted a change in their regular medication. The change could be either the initiation of additional treatment(s) or the intensification of a treatment the subject was already receiving, and the change must have been specifically to address the exacerbation event. COPD exacerbations occurring after the time of withdrawal or completion of the study were not included. (NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Perforomist Inhalation Solution | 142 |
| Matching Placebo | 135 |
The primary endpoint was the combined incidence of respiratory death, first COPD-related ER visit or first COPD exacerbation-related hospitalization (whichever occurred first from the time of randomization to the end of the study). The time-to-first event was measured and analyzed in units of weeks and was summarized by treatment for subjects in the Safety Set. An independent Mortality Adjudication Board was used to evaluate all deaths that occurred in the study and for assigning cause of death and COPD-relatedness. (NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Perforomist Inhalation Solution | 64 |
| Matching Placebo | 57 |
The primary endpoint was the combined incidence of respiratory death, first COPD-related ER visit or first COPD exacerbation-related hospitalization (whichever occurred first from the time of randomization to the end of the study). The time-to-first event was measured and analyzed in units of weeks and was summarized by treatment for subjects in the Safety Set. An independent Mortality Adjudication Board was used to evaluate all deaths that occurred in the study and for assigning cause of death and COPD-relatedness. (NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | percent (Number) |
|---|---|
| Perforomist Inhalation Solution | 15.5 |
| Matching Placebo | 14.9 |
COPD exacerbations were defined as events in the natural course of disease characterized by an increase from baseline in two of the following symptoms: dyspnea, cough, and sputum production that was beyond normal day-to-day variations, was acute in onset, that persisted for at least two consecutive days, and that warranted a change in their regular medication.The change could be either the initiation of additional treatment(s) or the intensification of a treatment the subject was already receiving, and the change must have been specifically to address the exacerbation event. COPD exacerbations occurring after the time of withdrawal or completion of the study were not included. (NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | percent (Number) |
|---|---|
| Perforomist Inhalation Solution | 34.7 |
| Matching Placebo | 34.0 |
The Transition Dyspnea Index (TDI) measures changes in dyspnea severity from the baseline as established by the BDI. It has 3 components: change in functional impairment, change in magnitude of task, and change in magnitude of effort, and each component is rated on a scale ranging from -3 (major deterioration) to +3 (major improvement). The 3 components are summed to provide a total score ranging from -9 to +9. The lower the score, the more deterioration in severity of dyspnea. (NCT01488019)
Timeframe: On treatment at months 3, 6, 9 and 12
| Intervention | units on a scale (Least Squares Mean) | |||
|---|---|---|---|---|
| Month 3 | Month 6 | Month 9 | Month 12 | |
| Matching Placebo | 0.0 | 0.4 | 0.4 | 0.6 |
| Perforomist Inhalation Solution | 0.7 | 0.5 | 0.7 | 0.5 |
(NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| Subjects with a COPD- related ER Visit | Subjects with a COPD-Related Hospitalization | |
| Matching Placebo | 47 | 43 |
| Perforomist Inhalation Solution | 46 | 39 |
An independent Mortality Adjudication Board was used to evaluate all deaths that occurred in the study and for assigning cause of death and COPD-relatedness. (NCT01488019)
Timeframe: 0 to 52 weeks
| Intervention | Participants (Number) | ||
|---|---|---|---|
| Incidence of All Cause Mortalities | Incidence of Respiratory Related Mortalities | Incidence of COPD Related Mortalities | |
| Matching Placebo | 10 | 1 | 1 |
| Perforomist Inhalation Solution | 3 | 0 | 0 |
"Saint Georges Respiratory Questionnaire comprises 50 items in 3 sections, Symptoms, Activity, Impact, measuring health status in chronic airflow limitation. Symptoms captures level of symptomatology. Activity and Impact responses are either yes or no. Scoring is from 0 to 100; 0 = no life quality impairment. A summary score for all items is calculated and ranges from 0 to 100, where 0 indicates best possible health status, 100 represents worst possible health status. Scores are calculated using weights attached to each item in the questionnaire - 4 unit changes are clinically meaningful." (NCT01488019)
Timeframe: On treatment at months 3, 6, 9 and 12
| Intervention | units on a scale (Least Squares Mean) | |||
|---|---|---|---|---|
| Change from Baseline SGRQ Total Score: Month 3 | Change from Baseline SGRQ Total Score: Month 6 | Change from Baseline SGRQ Total Score: Month 9 | Change from Baseline SGRQ Total Score: Month 12 | |
| Matching Placebo | -2.027 | -2.511 | -2.115 | -1.475 |
| Perforomist Inhalation Solution | -3.252 | -2.329 | -2.021 | -1.453 |
The standard deviation of the measure is expressed as the coefficient of variation (%) (NCT01551888)
Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)
| Intervention | pg/mL (Mean) |
|---|---|
| Formoterol 12 μg | 14.90 |
| Aclidinium/Formoterol 400/12 μg FDC | 16.72 |
The standard deviation of the measure is expressed as the coefficient of variation (%) (NCT01551888)
Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose; Days 2-4: 0, 5 and 15 min post dose; Day 5: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (post AM dose)
| Intervention | pg*hr/mL (Mean) |
|---|---|
| Formoterol 12 μg | 87.14 |
| Aclidinium/Formoterol 400/12 μg FDC | 85.15 |
The standard deviation of the measure is expressed as the coefficient of variation (%) (NCT01551888)
Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose
| Intervention | pg*hr/mL (Mean) |
|---|---|
| Formoterol 12 μg | 41.63 |
| Aclidinium/Formoterol 400/12 μg FDC | 42.27 |
The standard deviation of the measure is expressed as the coefficient of variation (%) (NCT01551888)
Timeframe: Day 1: 0, 5, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours (5 min before PM dose) and 5 and 15 min post PM dose
| Intervention | pg/mL (Mean) |
|---|---|
| Formoterol 12 μg | 8.23 |
| Aclidinium/Formoterol 400/12 μg FDC | 9.55 |
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. (NCT01566149)
Timeframe: Up to Week 12
| Intervention | participants (Number) |
|---|---|
| MF/F 200/10 mcg MDI BID | 0 |
| MF/F 400/10 mcg MDI BID | 1 |
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product. (NCT01566149)
Timeframe: Up to Week 14
| Intervention | participants (Number) |
|---|---|
| MF/F 200/10 mcg MDI BID | 5 |
| MF/F 400/10 mcg MDI BID | 8 |
A drug-related AE was defined as any AE for which there is reasonable possibility of drug relationship as assessed by the Investigator. (NCT01566149)
Timeframe: Up to Week 14
| Intervention | participants (Number) |
|---|---|
| MF/F 200/10 mcg MDI BID | 0 |
| MF/F 400/10 mcg MDI BID | 0 |
"A serious AE was defined as any untoward medical occurrence or effect that at~any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; and/or cancer." (NCT01566149)
Timeframe: Up to Week 14
| Intervention | participants (Number) |
|---|---|
| MF/F 200/10 mcg MDI BID | 0 |
| MF/F 400/10 mcg MDI BID | 0 |
Baseline was defined as the highest FEV1 value of three assessments prior to first dose of study drug. If two (or all three) spirometry efforts had identical FEV1, the FEV1 from the effort with the highest Forced Vital Capacity (FVC) was to be recorded. Week 12 FEV1 was assessed as the morning FEV1 at the end of the dosing interval (trough FEV1). For participants who discontinued prior to Week 12, the FEV1 measurement from the discontinuation visit was to be be carried forward to Week 12 if (and only if) the participant's study medication compliance rate prior to discontinuation was at least 85%. (NCT01566149)
Timeframe: Baseline and Week 12
| Intervention | liters (Mean) | ||
|---|---|---|---|
| Baseline FEV1 | Week 12 FEV1 | Change from Baseline in FEV1 at Week 12 | |
| MF/F 200/10 mcg MDI BID | 2.397 | 2.503 | 0.106 |
| MF/F 400/10 mcg MDI BID | 2.215 | 2.270 | 0.054 |
(NCT01572792)
Timeframe: Baseline of lead-in study to Week 52 of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | -0.086 |
| Aclidinium/Formoterol 400/12 μg | 0.198 |
| Aclidinium/Formoterol 400/6 μg | 0.166 |
| Aclidinium 400 μg | 0.112 |
| Formoterol 12 μg | 0.109 |
For each safety parameter, the last assessment made before the first dose of investigational product in the lead-in study (LAC MD-31) was used as the baseline for all analyses of that safety parameter in this extension study (NCT01572792)
Timeframe: Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52)
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 56.8 |
| Aclidinium/Formmoterol 400/12 μg | 65.9 |
| Aclidinium/Formoterol 400/6 μg | 61.3 |
| Aclidinium 400 μg | 67.5 |
| Formoterol 12 μg | 64.6 |
"Potentially clinically significant change:~>1.15 × upper limit of normal (ULN) for absolute cell count of basophils, eosinophils or monocytes, blood alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, total cholesterol, creatine kinase, creatinine, gamma glutamyl transferase, lactate dehydrogenase, triglycerides or uric acid <0.85 x lower limit of normal (LLN) or > 1.15 ULN for hematocrit ratio, haemoglobin, lymphocytes or neutrophils absolute cell count, platelet count (thrombocytes), red or white blood cell count, calcium, fasting glucose, phosphorus, total protein, or urinary pH <0.95 x LLN or >1.05 x ULN for chloride, potassium, sodium Urinary glucose ≥0.015, blood or ketones or protein ≥1 or specific gravity >1.1 × ULN~The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study" (NCT01572792)
Timeframe: Baseline of lead-in study to end of treatment (up to Week 52)
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 32.9 |
| Aclidinium/Formmoterol 400/12 μg | 41.2 |
| Aclidinium/Formoterol 400/6 μg | 35.3 |
| Aclidinium 400 μg | 32.5 |
| Formoterol 12 μg | 38.5 |
"Potentially clinically significant change:~Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline Pulse rate ≥110 bpm and increase ≥15% from baseline or ≤50 bpm and decrease ≥15% from baseline Weight increase or decrease ≥7% from baseline~The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study" (NCT01572792)
Timeframe: Baseline of lead-in study to end of treatment (up to Week 52)
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 27.4 |
| Aclidinium/Formmoterol 400/12 μg | 24.2 |
| Aclidinium/Formoterol 400/6 μg | 18.6 |
| Aclidinium 400 μg | 22.2 |
| Formoterol 12 μg | 24.5 |
"The TDI measures the change from baseline in severity of breathlessness in symptomatic patients. The TDI contains a rating for 3 categories (functional impairment, magnitude of task, magnitude of effort). TDI scale ranges from -3 (major deterioration) to +3 (major improvement) including a 0 score to indicate no change. The 3 categories are added to obtain a focal score ranging from -9 (including 0) to +9." (NCT01572792)
Timeframe: Baseline of lead-in study to Week 52 of treatment
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.731 |
| Aclidinium/Formoterol 400/12 μg | 1.812 |
| Aclidinium/Formoterol 400/6 μg | 1.742 |
| Aclidinium 400 μg | 1.596 |
| Formoterol 12 μg | 1.324 |
(NCT01572792)
Timeframe: Baseline of lead-in study to end of treatment (up to Week 52)
| Intervention | Percentage of participants (Number) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| QT interval change from baseline >30 msec | QT interval >480 msec | QTcB change from baseline >30 msec | QTcB >480 msec | QTcF change from baseline >30 msec | QTcF >480 msec | QRS interval ≥100 msec & ≥25% increase | PR interval ≥200 msec & ≥25% increase | Heart rate ≥110 bpm & ≥15% increase from baseline | Heart rate ≤50 bpm & ≥15% decrease from baseline | |
| Aclidinium 400 μg | 60.4 | 2.6 | 35.6 | 5.7 | 27.8 | 0.5 | 2.6 | 3.1 | 1.0 | 7.2 |
| Aclidinium/Formmoterol 400/12 μg | 53.8 | 3.8 | 37.0 | 8.3 | 28.7 | 0.6 | 6.6 | 2.2 | 2.7 | 6.0 |
| Aclidinium/Formoterol 400/6 μg | 55.9 | 2.9 | 39.7 | 9.8 | 30.4 | 1.0 | 3.9 | 1.0 | 1.0 | 8.3 |
| Formoterol 12 μg | 48.4 | 4.7 | 38.4 | 8.4 | 30.2 | 2.6 | 4.7 | 1.6 | 2.1 | 4.7 |
| Placebo | 53.4 | 3.4 | 36.3 | 7.5 | 27.4 | 2.1 | 6.2 | 2.8 | 0.7 | 11.0 |
St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 3 dimension scores (symptom, activity and impact). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status). (NCT01572792)
Timeframe: Baseline of lead-in study to Week 52 of treatment
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.862 |
| Aclidinium/Formoterol 400/12 μg | -3.646 |
| Aclidinium/Formoterol 400/6 μg | -5.527 |
| Aclidinium 400 μg | -4.306 |
| Formoterol 12 μg | -4.059 |
(NCT01572792)
Timeframe: Baseline of lead-in study to Week 52 of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Placebo | -0.101 |
| Aclidinium/Formoterol 400/12 μg | 0.038 |
| Aclidinium/Formoterol 400/6 μg | 0.005 |
| Aclidinium 400 μg | 0.030 |
| Formoterol 12 μg | 0.004 |
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative. (NCT01574651)
Timeframe: Baseline, week 26
| Intervention | Score on a scale (Mean) | |
|---|---|---|
| Baseline (n=452,441) | Week 26 (n=475,456) | |
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 44.70 | 41.30 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 45.68 | 43.19 |
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative. Superiority of QVA 110/50 μg to tiotropium 18 μg q.d. plus formoterol 12 μg b.i.d. in terms of health related quality of life as assessed by St George's Respiratory Questionnaire (SGRQ-C) after 26 weeks of treatment (NCT01574651)
Timeframe: Baseline, week 26
| Intervention | Score on a scale (Mean) | |
|---|---|---|
| Baseline (n=452,441) | Week 26 (n=475,456) | |
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 44.70 | 41.30 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 45.68 | 43.19 |
The number of participants with at least one moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. (NCT01574651)
Timeframe: Week 26
| Intervention | Participants (Number) |
|---|---|
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 62 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 70 |
Trough FEV1 is the mean value of FEV1 (forced expiratory volume in one second) measured at 23:15h and 23:45h after the morning doses. The baseline value was measured at day 1 prior to the first dose. (NCT01574651)
Timeframe: Baseline, Week 26
| Intervention | Liters (Mean) | |
|---|---|---|
| Baseline | Week 26 | |
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 1.329 | 1.495 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 1.313 | 1.409 |
FEV1 30min is the forced expiratory volume in one second measured 30 min after the morning dose. (NCT01574651)
Timeframe: Baseline, Week 26
| Intervention | Liters (Mean) | |
|---|---|---|
| Baseline (n=475,458) | Week 26 (n=476,458) | |
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 1.517 | 1.605 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 1.495 | 1.565 |
"Part I of the SGRQ-C covers symptoms and is concerned with respiratory symptoms, their frequency and severity. Each questionnaire response has a unique empirically derived weight. A score was calculated from these weights. The lowest possible value is zero and the highest 100. A higher value corresponds to greater impairment of health status." (NCT01574651)
Timeframe: Baseline, Week 26
| Intervention | Score on a scale (Mean) | |
|---|---|---|
| Baseline (n=473,457) | Week 26 (n=476,458) | |
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 64.10 | 58.31 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 64.29 | 60.16 |
Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. missing values were replaced by the latest observed value (LOCF) (NCT01574651)
Timeframe: Week 26
| Intervention | Units on a scale (Mean) |
|---|---|
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 1.34 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 0.87 |
The percent of patients with at least one severe exacerbation within the 26 weeks that required hospitalization. COPD exacerbations were considered to be severe if hospitalization were required. (NCT01574651)
Timeframe: Week 26
| Intervention | Percent of participants (Number) |
|---|---|
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 2.1 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 2.4 |
The percent of participants with at least one moderate exacerbation within the 26 weeks that required systemic corticosteroids and/or antibiotics during the treatment (NCT01574651)
Timeframe: Week 26
| Intervention | Percent of participants (Number) |
|---|---|
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | 10.9 |
| Tiotropium Plus Formoterol and Placebo to QVA149 | 13.3 |
AUC0-6 is area under the curve from time 0 to 6 hours Serial spirometry was performed at -60 min predose, at 5 (+5) and 30 (±5) min post-dose, and at 1, 2, 3, 4, and 6 hrs post-dose (±15 min) Change from baseline was baseline of each treatment period The normalized FEV1 AUC0-6 was calculated by means of the trapezoidal method, dividing the area under the curve by the corresponding time intervals (NCT01641081)
Timeframe: Baseline and up to 6 hrs post-dose (±15 min) on Day 14 of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Foradil 24 μg | 0.3196 |
| Foradil 12 μg | 0.3076 |
| Formoterol 12 μg | 0.2795 |
| Formoterol 6 μg | 0.2726 |
| Placebo | 0.0552 |
AUC0-6 is area under the curve from time 0 to 6 hours Serial spirometry was performed at -60 min predose, at 5 (+5) and 30 (±5) min post-dose, and at 1, 2, 3, 4, and 6 hrs post-dose (±15 min) Change from baseline was baseline of Period 1 The time-normalized FEV1 AUC0-6 was calculated by means of the trapezoidal method, dividing the area under the curve by the corresponding time intervals (NCT01641081)
Timeframe: Baseline and up to 6 hrs post-dose (±15 min) on Day 1 of treatment
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Foradil 24 μg | 0.3544 |
| Foradil 12 μg | 0.3068 |
| Formoterol 12 μg | 0.2712 |
| Formoterol 6 μg | 0.2204 |
| Placebo | 0.0306 |
Evaluation of lung hyperinflation as determined by Pulmonary function test where Inspiratory Capacity (IC) before and 45 minutes after the administration of the budesonide/formoterol or placebo. (NCT01760304)
Timeframe: Change from Baseline and after 45 minutes after administration of study medication or placebo
| Intervention | Liters (Mean) |
|---|---|
| Budesonide / Formoterol | 0.34 |
| Placebo | -0.058 |
Evaluation of O2 Pulse is the measurement of oxygen consumption pre and post intervention (NCT01760304)
Timeframe: Change from Baseline and 45 minutes after administration of study medication or placebo
| Intervention | ml/beat (Mean) |
|---|---|
| Budesonide / Formoterol | -0.03 |
| Placebo | 0.17 |
"Impedance cardiography (ICG) (BioZ Dx ICG machine, by CardioDynamics) was used to measure cardiac output without the need for invasive devices. Cardiac output measurement by impedance cardiography (CO-ICG) is a plethysmography technique using sensors to detect the properties of the blood flow in the thorax.~All subjects had on each visit a baseline measurement at rest and then 45 minutes after intervention (Budesonide/formoterol or Placebo). Measurement were performed at rest for 5 minutes to obtain a steady state and the last 2 minutes were taken for analysis as an averaged value labeled as pre and post intervention. For the analysis we calculated the difference from pre and post intervention at each visit. Paired t-test was used to compare the mean+/- SD of the pre and post difference when taking the study drug vs placebo." (NCT01760304)
Timeframe: Change from Baseline and at 45 minutes after administration of study medication or placebo
| Intervention | ml/beat (Mean) |
|---|---|
| Budesonide / Formoterol | -0.1 |
| Placebo | 1.9 |
(NCT01783821)
Timeframe: Baseline to Day 28
| Intervention | days (Median) |
|---|---|
| Budesonide and Formoterol | 4 |
| Placebo | 8 |
(NCT01783821)
Timeframe: Baseline to Day 28
| Intervention | days (Median) |
|---|---|
| Budesonide and Formoterol | 4 |
| Placebo | 6 |
ARDS was defined per Berlin definition. Chest radiographs of all ventilated (non-invasive or invasive) patients were reviewed as consistent or not consistent with ARDS by the site investigator. A second adjudication was performed by an alternate principal investigator blinded to subject identification and clinical data. Final diagnosis of ARDS was determined centrally after chest radiograph adjudication was considered together with other relevant clinical data. (NCT01783821)
Timeframe: Hospital discharge, approximately day 28
| Intervention | participants (Number) |
|---|---|
| Budesonide and Formoterol | 0 |
| Placebo | 7 |
(NCT01783821)
Timeframe: Hospital discharge, approximately day 28
| Intervention | participants (Number) |
|---|---|
| Budesonide and Formoterol | 6 |
| Placebo | 16 |
Oxygen saturation (SpO2) was measured by pulse oximetry. FiO2 is the assumed proportion of oxygen concentration participating in gas exchange in the alveoli. All S/F measurements were performed per standard operating protocol using a Venturi mask titrated to obtain an oxygen saturation of 94 ± 2% unless the patient met this goal on room air or clinical status dictated an alternative delivery mode. This outcome measure was analyzed as a longitudinal continuous variable by a mixed effect model. The formula for the calculation of SpO2/FiO2 (or S/F ratio) is %saturation/proportion of FiO2 concentration. (NCT01783821)
Timeframe: baseline to day 5 after the first treatment
| Intervention | SpO2/FiO2 Ratio (Median) | |||||
|---|---|---|---|---|---|---|
| Day 0 (29, 30) | Day 1 (29, 30) | Day 2 (25, 27) | Day 3 (17, 24) | Day 4 (13,19) | Day 5 (6,7) | |
| Budesonide and Formoterol | 320 | 376 | 400 | 396 | 448 | 375 |
| Placebo | 334 | 336 | 332 | 360 | 336 | 362 |
The data in the table below represent the greatest change from baseline observed for any one participant over all individual post-baseline measurements. (NCT01783821)
Timeframe: Days 0 - 5
| Intervention | participants (Number) | ||
|---|---|---|---|
| >20% Decrease | No change (within 20%) | > 20% Increase | |
| Budesonide and Formoterol | 0 | 11 | 18 |
| Placebo | 8 | 9 | 13 |
Enzyme immunosorbent assay system (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | Fold activation (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | 1.1 |
| Symbicort® Total Dose 400ug/12ug | 1.8 |
| Symbicort® Total Dose 800ug/24ug | 2.3 |
| Pulmicort 800ug | 2.1 |
Sputum TNF-alpha levels obtained from induced sputum compared to screening visit. (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | pg/mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | -4.8 |
| Symbicort® Total Dose 400ug/12ug | -5.7 |
| Symbicort® Total Dose 800ug/24ug | -7.8 |
| Pulmicort 800ug | -9.4 |
Improvement in FEV1 compared to baseline levels. (NCT01787097)
Timeframe: Baseline and 2 hours post inhalation
| Intervention | mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | 160 |
| Symbicort® Total Dose 400ug/12ug | 120 |
| Symbicort® Total Dose 800ug/24ug: | 200 |
| Pulmicort 800ug | 52 |
Changes in IL-6 Levels in the sputum supernatant compared to screening visit (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | pg/mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | -29 |
| Symbicort® Total Dose 400ug/12ug | -14 |
| Symbicort® Total Dose 800ug/24ug | -28 |
| Pulmicort 800 | -29 |
Changes in CXCL8 concentrations in sputum compared to screening visit. (NCT01787097)
Timeframe: Screening visit and 2 hours post inhalation of treatment
| Intervention | ng/mL (Mean) |
|---|---|
| Formoterol (FORM) Total Dose 24ug | -0.04 |
| Symbicort® Total Dose 400ug/12ug | -2.1 |
| Symbicort® Total Dose 800ug/24ug | -2.2 |
| Pulmicort 800 | -1.5 |
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. A positive change from baseline in FEV1 indicates improvement in lung function. Pulmonary function tests were performed at study visits including FEV1, and Force Vital Capacity (FVC). These were performed 30 minutes before treatment and not more than 2 hours in advance after stopping the long-acting bronchodilators eight hours before visits. In order to reduce the variation between each test, the same instrument was used in the whole research process if condition allowed. (NCT01794780)
Timeframe: Baseline,12 months
| Intervention | Liters (Mean) |
|---|---|
| Indacaterol | 0.056 |
| Tiotropium Bromide | -0.036 |
| LABA/ICS | 0.056 |
| Indacaterol +Tiotropium | 0.030 |
| LABA/ICS + Tiotropium | -0.028 |
| Oral Theophylline | 0.046 |
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. A positive change from baseline in FEV1 indicates improvement in lung function. Pulmonary function tests were performed at study visits including FEV1, and Force Vital Capacity (FVC). These were performed 30 minutes before treatment and not more than 2 hours in advance after stopping the Long-acting bronchodilators eight hours before visits. In order to reduce the variation between each test, the same instrument was used in the whole research process if condition allowed. (NCT01794780)
Timeframe: Baseline,3 months
| Intervention | Liters (Mean) |
|---|---|
| Indacaterol | -0.042 |
| Tiotropium | 0.006 |
| LABA/ICS | 0.033 |
| Indacaterol + Tiotropium | 0.022 |
| LABA/ICS + Tiotropium | 0.011 |
| Oral Theophylline | 0.012 |
Number of COPD exacerbations evaluated over 12 months. COPD exacerbation is defined as a new onset or worsening of at least 1 respiratory major symptoms (e.g. dyspnea, cough, sputum volume or sputum purulence) for at least 3 consecutive days, which results in recorded treatment change (antibiotics/steroids/oxygen therapy) OR recorded COPD related hospitalization/Emergency visit. COPD exacerbation is not considered as adverse event, and should only be recorded in COPD e-CRF. (NCT01794780)
Timeframe: Baseline,12 months
| Intervention | COPD Exacerbations/year (Mean) |
|---|---|
| Indacaterol | 1.1 |
| Tiotropium Bromide | 0.5 |
| Salmeterol/Fluticasone | 1.1 |
| Budesonide/ Formoterol | 0.4 |
| LABA/ICS | 0.9 |
| Indacaterol +Tiotropium | 4.1 |
| LABA/ICS + Tiotropium | 0.8 |
| Oral Theophylline | 1.0 |
The COPD assessment test (CAT) is a short instrument scale used to quantify the symptom burden of COPD and will be used to assess the health status of patients in this study. It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient. (NCT01794780)
Timeframe: Baseline,3,6,9,12 months
| Intervention | Score on a scale (Mean) | |||
|---|---|---|---|---|
| 3 Month | 6 Month | 9 Month | 12 Month | |
| Indacaterol | -1.9 | -1.9 | -4.4 | -5.1 |
| Indacaterol +Tiotropium | -1.9 | -2.7 | -9.0 | -7.7 |
| LABA/ICS | -2.3 | -2.7 | -3.5 | -4.1 |
| LABA/ICS + Tiotropium | -1.8 | -2.2 | -3.1 | -3.7 |
| Oral Theophylline | -1.8 | -2.5 | -3.1 | -2.4 |
| Tiotropium Bromide | -2.1 | -2.7 | -3.1 | -2.6 |
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. BDI/TDI was used to assess dyspnea from several aspects, caused by daily activities. These were evaluated by the investigators in the study at the scheduled study visits. The indices were to be evaluated by the same investigator.as far as possible. (NCT01794780)
Timeframe: Baseline,3,6,9,12 months
| Intervention | Units on a scale (Mean) | ||||
|---|---|---|---|---|---|
| Baseline | 3 Month | 6 Month | 9 Month | 12 Month | |
| Indacaterol | 6.7 | 1.4 | 0.0 | 0.7 | 0.3 |
| Indacaterol +Tiotropium | 5.4 | 0.4 | -0.5 | 1.0 | 1.0 |
| LABA/ICS | 6.7 | 1.3 | 1.4 | 1.6 | 1.7 |
| LABA/ICS + Tiotropium | 6.2 | 1.1 | 0.9 | 0.9 | 1.0 |
| Oral Theophylline | 7.1 | 0.9 | 1.2 | 1.4 | 1.6 |
| Tiotropium Bromide | 6.6 | 1.2 | 1.0 | 0.9 | 1.0 |
The mMRC scale is scored from 0 (less severe) to 4 (severe). 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing. The modified Medical Research Council (mMRC) Dyspnea Scale , is a five-item instrument (part of the Borg scale) to assess a patient's degree of breathlessness in relation to physical activity. Participants will be required to read a brief description of an activity and then select a statement that best describes their experience with dyspnea at Visit 101. The mMRC was assessed by the investigators at the scheduled visits. (NCT01794780)
Timeframe: Baseline,3,6,9,12 months
| Intervention | Number of participants (Number) | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline scale item 0 | Baseline scale item 1 | Baseline scale item 2 | Baseline scale item 3 | Baseline scale item 4 | 3 month Scale item 0 | 3 month Scale item 1 | 3 month Scale item 2 | 3 month Scale item 3 | 3 month Scale item 4 | 6 month Scale item 0 | 6 month Scale item 1 | 6 month Scale item 2 | 6 month Scale item 3 | 6 month Scale item 4 | 9 month Scale item 0 | 9 month Scale item 1 | 9 month Scale item 2 | 9 month Scale item 3 | 9 month Scale item 4 | 12 month Scale item 0 | 12 month Scale item 1 | 12 month Scale item 2 | 12 month Scale item 3 | 12 month Scale item 4 | |
| Indacaterol | 4 | 11 | 14 | 3 | 0 | 3 | 9 | 7 | 1 | 0 | 2 | 5 | 8 | 1 | 0 | 3 | 5 | 4 | 1 | 0 | 1 | 5 | 2 | 2 | 0 |
| Indacaterol +Tiotropium | 1 | 4 | 1 | 3 | 0 | 0 | 4 | 3 | 0 | 0 | 0 | 1 | 4 | 1 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 2 | 1 | 0 | 0 |
| LABA/ICS | 161 | 435 | 327 | 154 | 19 | 101 | 364 | 203 | 67 | 6 | 96 | 290 | 138 | 54 | 5 | 116 | 256 | 131 | 42 | 4 | 150 | 275 | 127 | 41 | 9 |
| LABA/ICS + Tiotropium | 63 | 226 | 211 | 110 | 22 | 54 | 157 | 133 | 58 | 9 | 37 | 149 | 105 | 44 | 11 | 45 | 127 | 99 | 41 | 9 | 47 | 138 | 102 | 32 | 9 |
| Oral Theophylline | 31 | 66 | 34 | 19 | 4 | 20 | 52 | 26 | 11 | 1 | 15 | 43 | 20 | 4 | 0 | 20 | 40 | 19 | 5 | 1 | 20 | 52 | 12 | 4 | 1 |
| Tiotropium Bromide | 40 | 114 | 83 | 36 | 3 | 24 | 69 | 54 | 18 | 2 | 23 | 57 | 45 | 13 | 3 | 24 | 52 | 30 | 14 | 1 | 24 | 61 | 33 | 10 | 3 |
Examinations were performed by a qualified professional. (NCT01803555)
Timeframe: Baseline, Week 4, Week 8, Week 12
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Baseline | Week 4 | Week 8 | Week 12 | |
| BF Spiromax | 0 | 1 | 1 | 2 |
| Symbicort Turbohaler | 0 | 0 | 2 | 3 |
Swab samples were collected by a qualified professional. (NCT01803555)
Timeframe: Baseline, Week 4, Week 8, Week 12
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Baseline | Week 4 | Week 8 | Week 12 | |
| BF Spiromax | 1 | 0 | 0 | 1 |
| Symbicort Turbohaler | 0 | 0 | 0 | 1 |
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. (NCT01803555)
Timeframe: Baseline up to Week 12
| Intervention | Participants (Count of Participants) |
|---|---|
| BF Spiromax | 117 |
| Symbicort Turbohaler | 106 |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline trough morning PEF was defined as the average value of recorded (nonmissing) morning assessments 5 out of the last 7 days prior to randomization. The first day before randomization consisted of the electronic patient diary entry at home on the morning of the randomization visit (Baseline [Day 1]) and the first day postrandomization consisted of the electronic patient diary entry at home on the morning of the day after the randomization visit (Baseline [Day 1]). For postdose weekly average of trough morning PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of morning PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks. (NCT01803555)
Timeframe: Baseline, Weeks 1 to 12 (averaged over 12 weeks)
| Intervention | liters (L)/minute (min) (Least Squares Mean) |
|---|---|
| BF Spiromax | 18.839 |
| Symbicort Turbohaler | 21.796 |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Baseline was defined as the average value of the recorded (nonmissing) assessments over the 7 days prior to randomization. For postdose weekly average of evening PEF measurements, the values were the averages based on the available data for that week. The averages were calculated as the sum of evening PEF values divided by the number of nonmissing assessments. The final value for change from baseline was calculated as the average of the weekly change from baseline averaged over 12 weeks. (NCT01803555)
Timeframe: Baseline, Weeks 1 to 12 (averaged over 12 weeks)
| Intervention | L/min (Least Squares Mean) |
|---|---|
| BF Spiromax | 18.661 |
| Symbicort Turbohaler | 21.740 |
Number of asthma exacerbations events (NCT01845025)
Timeframe: 26 weeks
| Intervention | events (Mean) |
|---|---|
| FOM 12 mcg + FP | 1.3 |
| Fluticasone Propionate (FP) | 1.2 |
Unplanned healthcare utilization by visit (Telephone contact with study doctor (MD); Telephone contact with other physician (MD) or healthcare provider (HCP); Unscheduled or unplanned visit to study doctor (including home visits); Unscheduled or unplanned visit to other physician or healthcare provider (including home visits); Emergency department or hospital visit (< 24 hours); Hospital admission or Emergency department visit (> 24 hours). (NCT01845025)
Timeframe: Week 4, Week 12, and Week 26
| Intervention | unplanned visits (Number) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Telephone contact with study MD: V3 | Telephone contact with other MD or HCP: V3 | unplanned visit to study MD;include home:V3 | unplanned visit to other MD or HCP incl.home:V3 | Emergency or hospital visit (< 24 hours):V3 | Hospital admission or Emergency visit (>24hrs):V3 | Telephone contact with study MD: V4 | Telephone contact with other MD or HCP: V4 | unplanned visit to study MD;include home:V4 | unplanned visit to other MD or HCP incl.home:V4 | Emergency or hospital visit (< 24 hours):V4 | Hospital admission or Emergency visit (>24hrs):V4 | Telephone contact with study MD: V5 | Telephone contact with other MD or HCP: V5 | unplanned visit to study MD;include home:V5 | unplanned visit to other MD or HCP incl.home:V5 | Emergency or hospital visit (< 24 hours):V5 | Hospital admission or Emergency visit (>24hrs):V5 | |
| Fluticasone Propionate (FP) | 18 | 9 | 13 | 9 | 4 | 1 | 17 | 7 | 15 | 16 | 4 | 2 | 9 | 2 | 9 | 7 | 6 | 0 |
| FOM 12 mcg + FP | 19 | 5 | 7 | 5 | 3 | 1 | 25 | 5 | 10 | 15 | 3 | 0 | 14 | 8 | 6 | 10 | 4 | 2 |
The primary safety endpoint was the number of first occurrence(s) of any composite endpoint. The composite events include asthma-related deaths, asthma-related intubations and asthma-related hospitalizations. The number of events includes all adjudication confirmed events, one patient could experience multiple events during the course of study; Event rate = 100 * n patients with any events / total N patients in treatment group. (NCT01845025)
Timeframe: 26 weeks
| Intervention | number of occurences (Number) | |||
|---|---|---|---|---|
| Composite event | Asthma-related death | Asthma-related intubation | Asthma-related hospitalization | |
| Fluticasone Propionate (FP) | 3 | 0 | 0 | 3 |
| FOM 12 mcg + FP | 3 | 0 | 0 | 3 |
Percentage of days with no symptoms during the treatment period (26 weeks). Percentage is calculated as total number of days with no symptoms divided by total days of treatment. (NCT01845025)
Timeframe: 26 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| FOM 12 mcg + FP | 79.47 |
| Fluticasone Propionate (FP) | 77.64 |
Percentage of rescue free days is calculated as total number of days with no rescue medication was taken divided by total days of treatment. (NCT01845025)
Timeframe: 26 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| FOM 12 mcg + FP | 76.97 |
| Fluticasone Propionate (FP) | 73.29 |
Percentage of days with nighttime awakenings during the treatment period (26 weeks) (NCT01845025)
Timeframe: 26 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| FOM 12 mcg + FP | 4.55 |
| Fluticasone Propionate (FP) | 4.20 |
The percentage of days with limited ability to perform normal daily activities during the treatment period (26 weeks). Percentage is calculated as total number of days when the patient had limited ability to perform normal daily activities divided by total days of treatment. (NCT01845025)
Timeframe: 26 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| FOM 12 mcg + FP | 4.73 |
| Fluticasone Propionate (FP) | 4.75 |
The percentage of days of school/work missed during the treatment period (26 weeks). Overall percentage of school days missed for each student patient or of work days missed is calculated by total number of days missed divided by total days of treatment. (NCT01845025)
Timeframe: 26 weeks
| Intervention | percentage of days (Mean) |
|---|---|
| FOM 12 mcg + FP | 0.97 |
| Fluticasone Propionate (FP) | 0.56 |
Change from baseline in Asthma control Questionnaire (ACQ - 6) total score at week 26. Results of the Asthma control questionnaire (ACQ-6); The average score of the six questions is calculated as the sum of scores divided by the number of questions that were answered at the time point, as long as there were at least 4 questions answered. The ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ. The ACQ is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a total score of 0 corresponds to no impairment and a total score of 6 corresponds to maximum impairment. (NCT01845025)
Timeframe: baseline and 26 weeks
| Intervention | total score on a scale (Mean) |
|---|---|
| FOM 12 mcg + FP | -0.65 |
| Fluticasone Propionate (FP) | -0.59 |
Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (NCT01854658)
Timeframe: 24 weeks
| Intervention | Puffs / Day (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | -0.7 |
| GP MDI (PT001) | -0.4 |
| GFF MDI (PT003) | -1.0 |
| Placebo MDI | 0.0 |
Change from baseline in the SGRQ total score at Week 24. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. (NCT01854658)
Timeframe: 24 weeks
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | -2.3 |
| GP MDI (PT001) | -2.2 |
| GFF MDI (PT003) | -3.0 |
| Placebo MDI | -1.2 |
Defined as the first time-point using the 5- and 15-minute post dose measurements where the difference in FEV1 from Placebo was statistically significant (NCT01854658)
Timeframe: Day 1
| Intervention | Liters (Least Squares Mean) | |
|---|---|---|
| 5 min post dose | 15 min post dose | |
| FF MDI (PT005) | 0.175 | 0.212 |
| GFF MDI (PT003) | 0.192 | 0.237 |
| GP MDI (PT001) | 0.052 | 0.109 |
| Placebo MDI | 0.006 | 0.022 |
Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 (NCT01854658)
Timeframe: At week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | 0.268 |
| GP MDI (PT001) | 0.223 |
| GFF MDI (PT003) | 0.350 |
| Placebo MDI | 0.083 |
Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) at Week 24. (NCT01854658)
Timeframe: At Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | 0.061 |
| GP MDI (PT001) | 0.063 |
| GFF MDI (PT003) | 0.116 |
| Placebo MDI | 0.013 |
Change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1) over 24 weeks. FEV1 was assessed at multiple time points post-baseline, and a model-based average of all visits starting from Week 2 through week 24 inclusive was calculated. The change values reported in the table represent the change between the baseline and the average FEV1 post-baseline. (NCT01854658)
Timeframe: Over 24 weeks
| Intervention | Liters (Least Squares Mean) |
|---|---|
| FF MDI (PT005) | 0.080 |
| GP MDI (PT001) | 0.082 |
| GFF MDI (PT003) | 0.137 |
| Placebo MDI | 0.008 |
Peak FEV1 define at the highest value observed in the 3h after the morning IMP administration (NCT01908140)
Timeframe: At Week 24
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Aclidinium Bromide / Formoterol Fumarate | 1.655 |
| Salmeterol / Fluticasone | 1.562 |
"The TDI includes the same 3 categories as BDI and 7 ratings indicating the magnitude of the change from baseline in each category: from -3 (major deterioration) to zero (no change) to +3 (major improvement). Category scores are added to compute the Focal Score (from -9 to 9)" (NCT01908140)
Timeframe: At Week 24
| Intervention | TDI Focal Score (Least Squares Mean) |
|---|---|
| Aclidinium Bromide / Formoterol Fumarate | 1.9 |
| Salmeterol / Fluticasone | 1.9 |
Participants /parent/legal guarding reported number of missed days of school or work at each study visit via diaries. (NCT01912872)
Timeframe: 12 month treatment duration
| Intervention | days (Number) | |
|---|---|---|
| Missed school days | Missed work days | |
| Adult Patients: Budesonide and Formoterol | 0 | 1 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 1 | 0 |
| Pediatric Patients: Budesonide and Formoterol | 3 | 1 |
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 2 | 0 |
prescribed budesonide dose (in μg) at Baseline in intention to treat population and in intention to treat population (NCT01912872)
Timeframe: Baseline
| Intervention | μg (Mean) | |
|---|---|---|
| ITT | PP | |
| Adult Patients: Budesonide and Formoterol | 533.3 | 533.3 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 580.0 | 575.0 |
| Pediatric Patients: Budesonide and Formoterol | 270.6 | 250.0 |
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 337.5 | 363.6 |
The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal (NCT01912872)
Timeframe: 12 month treatment duration
| Intervention | participants (Number) |
|---|---|
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 9 |
| Pediatric Patients: Budesonide and Formoterol | 15 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 34 |
| Adult Patients: Budesonide and Formoterol | 33 |
A hospital admission is defined as admissions to hospital involving a stay of at least 24 hours. (NCT01912872)
Timeframe: 12 month treatment duration
| Intervention | hospital admissions (Number) |
|---|---|
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 0 |
| Pediatric Patients: Budesonide and Formoterol | 1 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 0 |
| Adult Patients: Budesonide and Formoterol | 0 |
The Asthma Control Questionnaire (ACQ) has six questions to be answered by the participants, each with a 7 point scale (0-good control, 6-poor control), and one question where the actual pre-bronchodilator Forced expiratory volume in 1 second (FEV1) value expressed in % of predicted FEV1 was classified to scores from 0 (> 95% of predicted) to 6 (< 50% of predicted). The overall score is the average of the 7 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma. (NCT01912872)
Timeframe: Baseline
| Intervention | scores on a scale (Mean) |
|---|---|
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 3.3 |
| Pediatric Patients: Budesonide and Formoterol | 3.3 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 3.6 |
| Adult Patients: Budesonide and Formoterol | 3.3 |
The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal (NCT01912872)
Timeframe: 12 month treatment duration
| Intervention | percentage of participants (Number) |
|---|---|
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 62.5 |
| Pediatric Patients: Budesonide and Formoterol | 70.6 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 82.5 |
| Adult Patients: Budesonide and Formoterol | 71.8 |
Number of days of concomitant medications use reported by participants at all visits via diaries. (NCT01912872)
Timeframe: 12 month treatment duration
| Intervention | Number of days (Mean) |
|---|---|
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 7.3 |
| Pediatric Patients: Budesonide and Formoterol | 16.5 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 28.0 |
| Adult Patients: Budesonide and Formoterol | 16.3 |
The quality of life will be measured by the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]) score for adults and the pediatric version of the AQLQ(S) for pediatric participants (PAQLQ[S]) . The AQLQ(S) and PAQLQ(S0 contain 4 domains (activity limitations, symptoms, emotional function, and environmental stimuli), with a total of 32 items; each item is measured in a 7-point Likert scale of 1 to 7 (1 = severe impairment, 7 = no impairment). All items are weighted equally. Mean score is calculated across all items within each domain and the overall score is the mean score of the 32 items. (NCT01912872)
Timeframe: Baseline
| Intervention | scores on a scale (Mean) | ||||
|---|---|---|---|---|---|
| Overall | Symptoms domain | Activity limitations domain | Emotional functions domain | Environmental stimuli domain | |
| Adult Patients: Budesonide and Formoterol | 3.4 | 3.5 | 3.5 | 3.2 | 3.1 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 2.9 | 2.8 | 3.2 | 2.5 | 2.7 |
| Pediatric Patients: Budesonide and Formoterol | 3.4 | 3.3 | 3.3 | 3.6 | NA |
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 3.2 | 3.2 | 3.2 | 3.2 | NA |
The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal (NCT01912872)
Timeframe: 12 month treatment duration
| Intervention | Number of days (Mean) | |
|---|---|---|
| Wheezing | Night time cough | |
| Adult Patients: Budesonide and Formoterol | 29.0 | 32.3 |
| Adult Patients: Omalizumab + Budesonide and Formoterol | 25.4 | 20.6 |
| Pediatric Patients: Budesonide and Formoterol | 21.1 | 20.8 |
| Pediatric Patients: Omalizumab + Budesonide and Formoterol | 15.4 | 12.8 |
Asthma Control Questionnaire measured at each office visit. ACQ integrates values by 6 clinical questions related to symptoms and the value related to FEV1% predicted with a total score ranging from 0-6 and higher values indicating poorer asthma control. (NCT02045875)
Timeframe: Baseline, one, two and three months
| Intervention | units on a scale (Mean) | |||
|---|---|---|---|---|
| baseline | one month | two month | three month | |
| Dulera Adherence Monitoring | 1.857 | 1.792 | 1.345 | 1.105 |
| Dulera Standard of Asthma Care | 1.592 | 1.578 | 1.488 | 1.407 |
"Subjects in the monitoring group will have adherence greater than or equal to the 60% benchmark~Adherence was calculated by taking the number of doses actually taken divided by the number of doses prescribed and multiplying by 100." (NCT02045875)
Timeframe: week 2. months 1, 2, and 3
| Intervention | percent of prescribed doses (Mean) | |||
|---|---|---|---|---|
| week 2 | month 1 | month 2 | month 3 | |
| Dulera Adherence Monitoring | 88.75 | 80.7 | 77.55 | 76.8 |
"Subjects in the monitoring group will have adherence greater than or equal to the 60% benchmark~Overall interval value was the mean of daily percent" (NCT02045875)
Timeframe: 3 months
| Intervention | percent of prescribed doses per day (Mean) |
|---|---|
| Dulera Adherence Monitoring | 80.95 |
Asthma symptom score (eDiary) change from baseline during the randomised treatment period. Symptom score is entered morning and evening by the patient on a 4-point scale from 0 to 3 with higher values indicating more severe symptoms. Asthma symptom score is then the sum of the day and night scores, which implies a range of scores from 0 - 6, with higher values indicating more severe symptoms. Baseline is defined as the mean of all non-missing measurements during the last 10 days of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | -0.23 |
| Placebo Bid + Terbutaline 'as Needed' | -0.11 |
| Pulmicort Bid + Terbutaline 'as Needed' | -0.32 |
Asthma Quality of Life Questionnaire Standardised Version (AQLQ (S) overall score change from baseline. AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. (NCT02149199)
Timeframe: Study weeks 0,16,28,40,52
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 0.313 |
| Placebo Bid + Terbutaline 'as Needed' | 0.186 |
| Pulmicort Bid + Terbutaline 'as Needed' | 0.415 |
Asthma Control Questionnaire 5-item version score change from baseline. ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. (NCT02149199)
Timeframe: Study weeks 0,4,16,28,40,52
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | -0.33 |
| Placebo Bid + Terbutaline 'as Needed' | -0.17 |
| Pulmicort Bid + Terbutaline 'as Needed' | -0.48 |
Severe asthma exacerbations over the randomised treatment period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | exacerbations per year (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 0.07 |
| Placebo Bid + Terbutaline 'as Needed' | 0.20 |
| Pulmicort Bid + Terbutaline 'as Needed' | 0.09 |
Moderate or severe asthma exacerbations during the randomised treatment period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | exacerbations per year (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 0.14 |
| Placebo Bid + Terbutaline 'as Needed' | 0.36 |
| Pulmicort Bid + Terbutaline 'as Needed' | 0.15 |
A well-controlled asthma week is defined as the fulfilment of both conditions A) and B) below: A) Two or more of the following criteria are fulfilled: - No more than 2 days with a daily asthma symptom score >1 - No more than 2 days of 'as needed' medication use, up to a maximum of 4 occasions per week (multiple occasions per day should be regarded as separate occasions) - Morning PEF ≥80% of Predicted Normal every day B) Both of the following criteria are fulfilled: - No nighttime awakenings due to asthma - No additional inhaled and/or systemic glucocorticosteroid treatment due to asthma. The binary variable well-controlled asthma week was derived for each patient and study week. In addition, for each week, the percent of patients with well-controlled asthma week was derived. It is required that the eDiary had to be completed on at least 5 days in a week to be a well-controlled asthma week. (NCT02149199)
Timeframe: Weekly, up to 52 weeks
| Intervention | Percentage (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 34.4 |
| Placebo Bid + Terbutaline 'as Needed' | 31.1 |
| Pulmicort Bid + Terbutaline 'as Needed' | 44.4 |
"A moderate exacerbation is defined as a deterioration of asthma requiring a change in treatment, i.e. initiation of prescribed additional ICS treatment to avoid progression of the worsening of asthma to a severe exacerbation.~A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids" (NCT02149199)
Timeframe: Day 1 up to 52 weeks
| Intervention | Participants (Number) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 131 |
| Placebo Bid + Terbutaline 'as Needed' | 274 |
| Pulmicort Bid + Terbutaline 'as Needed' | 143 |
Morning peak expiratory flow (eDiary) change from baseline over the randomised treatment period. Baseline is defined as the mean of all non-missing morning measurements during the last 10 days of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | -3.97 |
| Placebo Bid + Terbutaline 'as Needed' | -15.92 |
| Pulmicort Bid + Terbutaline 'as Needed' | 6.01 |
Evening peak expiratory flow (eDiary) change from baseline during the randomised treatment period. Baseline is defined as the mean of all non-missing evening measurements during the last 10 days of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | L/min (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | -11.20 |
| Placebo Bid + Terbutaline 'as Needed' | -22.15 |
| Pulmicort Bid + Terbutaline 'as Needed' | -4.97 |
A poorly-controlled asthma week is defined as a week meeting any one of the following conditions: Two or more consecutive days with awakenings due to asthma on both nights; A recorded use of 'as needed' medication for symptom relief of at least 3 occasions per day, for at least 2 consecutive days; Additional systemic GCS treatment required for severe exacerbation. If there were sufficient data within a week available to confirm the week was not poorly-controlled, the week is labelled as 'does not meet criteria for poorly-controlled'. (NCT02149199)
Timeframe: Weekly for up to 52 weeks
| Intervention | weeks (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 7.7 |
| Placebo Bid + Terbutaline 'as Needed' | 9.7 |
| Pulmicort Bid + Terbutaline 'as Needed' | 6.7 |
ICS controller use days (%) during the randomised treatment period is calculated as the cumulative number of days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma exacerbations and/or long term poor asthma control (all treatment groups), divided by the number of days in the randomised treatment period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | % of days (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 30.8 |
| Placebo Bid + Terbutaline 'as Needed' | 5.6 |
| Pulmicort Bid + Terbutaline 'as Needed' | 85.6 |
Study specific asthma related discontinuation (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | Participants (Number) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 4 |
| Placebo Bid + Terbutaline 'as Needed' | 21 |
| Pulmicort Bid + Terbutaline 'as Needed' | 6 |
A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids (NCT02149199)
Timeframe: Day 1 up to 52 weeks
| Intervention | Participants (Number) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 71 |
| Placebo Bid + Terbutaline 'as Needed' | 152 |
| Pulmicort Bid + Terbutaline 'as Needed' | 78 |
Additional steroids for asthma includes any additional inhaled and/or systemic glucocorticosteroids treatment due to asthma while in the randomised treatment period. (NCT02149199)
Timeframe: Day 1 up to 52 weeks
| Intervention | Participants (Number) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 164 |
| Placebo Bid + Terbutaline 'as Needed' | 345 |
| Pulmicort Bid + Terbutaline 'as Needed' | 187 |
Night-time awakenings (%) due to asthma change from baseline. Variable analysed is the proportion (%) of nights during the relevant period with night-time awakenings. Baseline refers to the last 10 nights of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | % of nights (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | -7.5 |
| Placebo Bid + Terbutaline 'as Needed' | -4.6 |
| Pulmicort Bid + Terbutaline 'as Needed' | -9.8 |
Symptom-free days (%) change from baseline during the randomised treatment period.Variable analysed is the proportion (%) of symptom-free days during the relevant period. Baseline refers to the last 10 days of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | % of days (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 4.2 |
| Placebo Bid + Terbutaline 'as Needed' | 1.3 |
| Pulmicort Bid + Terbutaline 'as Needed' | 6.8 |
Asthma control days (%) change from baseline. An asthma control day is defined as the fulfilment of all of the following criteria; a day and night with no asthma symptoms, a night with no awakenings due to asthma symptoms and a day and night with no use of 'as needed' medication. Variable analysed is the proportion (%) of asthma control days during the randomised treatment period. Baseline refers to the last 10 days of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | % of days (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 13.2 |
| Placebo Bid + Terbutaline 'as Needed' | 12.8 |
| Pulmicort Bid + Terbutaline 'as Needed' | 18.5 |
'As needed' free days (%) change from baseline during the randomised treatment period. An 'as needed' free day is defined as a day and night with no use of 'as needed' medication. Variable analysed is the proportion (%) of 'as needed' free days during the relevant period. Baseline refers to the last 10 days of the run-in period. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | % of days (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 44.2 |
| Placebo Bid + Terbutaline 'as Needed' | 45.0 |
| Pulmicort Bid + Terbutaline 'as Needed' | 51.7 |
Overall estimate of FEV1 (mL) pre-bronchodilator change from baseline. Baseline is the measurement at Visit 3 (prior to first dose of Investigational Product) from MMRM (mixed model repeated measures analysis). (NCT02149199)
Timeframe: Study weeks 0,4,16,28,40,52
| Intervention | mL (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | 65 |
| Placebo Bid + Terbutaline 'as Needed' | 11.2 |
| Pulmicort Bid + Terbutaline 'as Needed' | 119.3 |
'As needed' inhalations change from baseline over the randomised treatment period. Baseline is defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day. (NCT02149199)
Timeframe: up to 52 weeks
| Intervention | Number of inhalations per day (Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' | -0.95 |
| Placebo Bid + Terbutaline 'as Needed' | -0.82 |
| Pulmicort Bid + Terbutaline 'as Needed' | -1.06 |
FEV1 from pre-dose spirometry is a measurement of lung function. The change from baseline on pre-dose FEV1 was summarized and compared between Symbicort and Formoterol groups using a mixed model. (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | L (Mean) |
|---|---|
| Symbicort pMDI | 0.008 |
| Formoterol Turbuhaler | -0.025 |
"The number of patients who developed moderate or severe COPD exacerbation during treatment period were reported. Cox proportional hazards regression model was fitted to data to compare the two treatment arms .~The hazard ratio and 95% CI were estimated." (NCT02157935)
Timeframe: From randomzation to EoT W 26
| Intervention | Participants (Number) |
|---|---|
| Symbicort pMDI | 171 |
| Formoterol Turbuhaler | 204 |
"Nighttime awakening due to COPD symptoms correspond to the severity of nocturnal symptoms from COPD.~The average number of awakening per night over the treatment period was analyzed. It was derived as the number of night with awakening divided by the total number of nights with data in the recording period. Change from baseline period on awakening was summarized and compared between two arms using a mixed model." (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | awakening/night (Mean) |
|---|---|
| Symbicort pMDI | -0.007 |
| Formoterol Turbuhaler | 0.021 |
"SGRQ is a standardized, self-administered tool for measuring impaired health and perceived wellbeing in respiratory diseases; a validated electronic version of the questionnaire in the relevant validated languages was used in this study.~The questionnaire contains 50 items divided into three dimensions (Symptoms, Activity and Impact).~Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100:~zero (0) score indicating no impairment of quality of life.~The total SGRQ score ranging from 0 to 100 is a summary score utilizing responses to all items calculated using weights attached to each item of the questionnaire.~Higher scores indicate poorer health and change of 4 units in the SGRQ has been determined to be the threshold for a clinically relevant change in health status.~The change from baseline was statistically summarized and compared between two arms in a mixed model." (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | scores on a scale (Mean) |
|---|---|
| Symbicort pMDI | -0.855 |
| Formoterol Turbuhaler | 0.442 |
"Use of rescue medication is a measure of symptoms that need to be treated with a short-acting bronchodilator.~The average daily use across the observation period was used for analysis. Change from baseline was summarized and compared between two arms using a mixed model." (NCT02157935)
Timeframe: From Run-in W -4 to EoT W 26
| Intervention | puffs/day (Mean) |
|---|---|
| Symbicort pMDI | 0.135 |
| Formoterol Turbuhaler | 0.343 |
"The annual COPD exacerbation rate was analyzed and compared between two arms.~Annual exacerbation rate for each subject is defined as number of exacerbations divided by duration of randomized treatment period in years.~The annual COPD exacerbation rate of Symbicort group was compared with annual rate of Formoterol group. The rate ratio of Symbicort vs. Formoteroal was assessed by a negative binomial model.~Exacerbations, that met the modified Anthonisen criteria and duration ≥2 days were classified as moderate and severe exacerbations.~Moderate exacerbation: treatment of symptoms with systemic corticosteroids (≥3 days) and/or antibiotics.~Severe exacerbation: symptoms that require hospitalization (including >24 hours in ED/urgent care setting)." (NCT02157935)
Timeframe: Randomization at Week 0 to End of Treatment (EoT) W 26
| Intervention | COPD exacerbations per year (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 0.85 |
| Formoterol Turbuhaler | 1.12 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (NCT02196714)
Timeframe: Day 1
| Intervention | L/h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 657.91 |
| GFF MDI 14.4/9.6 ug | 449.10 |
| GP MDI 28.8 µg | 785.60 |
| GP MDI 14.4 µg | 423.12 |
Change in QTc Fridericia's Interval from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | msec (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -4.8 |
| GFF MDI 14.4/9.6 ug | -5.4 |
| GP MDI 28.8 ug | -10.8 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (Cmax) (NCT02196714)
Timeframe: Day 1
| Intervention | pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 10.74 |
| GFF MDI 14.4/9.6 ug | 11.99 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (Cmax) (NCT02196714)
Timeframe: Day 1
| Intervention | pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 15.23 |
| GFF MDI 14.4/9.6 ug | 9.09 |
| GP MDI 28.8 ug | 16.85 |
| GP MDI 14.4 µg | 7.26 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (NCT02196714)
Timeframe: Day 1
| Intervention | 1/h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 0.1412 |
| GFF MDI 14.4/9.6 ug | 0.1470 |
Change in Heart Rate from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | Beats/Min (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 11.3 |
| GFF MDI 14.4/9.6 ug | 9.3 |
| GP MDI 28.8 ug | 4.5 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (AUC 0-t) (NCT02196714)
Timeframe: Day 1
| Intervention | h*pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 53.52 |
| GFF MDI 14.4/9.6 ug | 21.37 |
| GP MDI 28.8 ug | 64.05 |
| GP MDI 14.4 µg | 23.72 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (AUC 0-t) (NCT02196714)
Timeframe: Day 1
| Intervention | h*pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 45.96 |
| GFF MDI 14.4/9.6 ug | 42.39 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (AUC 0-12) (NCT02196714)
Timeframe: Day 1
| Intervention | h*pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 45.43 |
| GFF MDI 14.4/9.6 ug | 21.75 |
| GP MDI 28.8 ug | 50.59 |
| GP MDI 14.4 ug | 24.72 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (AUC 0-12) (NCT02196714)
Timeframe: Day 1
| Intervention | h*pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 44.15 |
| GFF MDI 14.4/9.6 ug | 42.54 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (AUC 0-∞) (NCT02196714)
Timeframe: Day 1
| Intervention | h*pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 46.26 |
| GFF MDI 14.4/9.6 ug | 32.18 |
| GP MDI 28.8 µg | 37.32 |
| GP MDI 14.4 µg | 34.04 |
Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 Hours
| Intervention | Ratio (Mean) | |||||
|---|---|---|---|---|---|---|
| Basophils/leukocytes (ratio) | Eosinophils/leukocytes (ratio) | Granulocytes/leukocytes (ratio) | Hematocrit (ratio) | Lymphocytes/leukocytes (ratio) | Monocytes/leukocytes (ratio) | |
| GFF MDI 14.4/9.6 ug | -0.0013 | 0.0026 | 0.0003 | -0.041 | -0.0019 | 0.0004 |
| GFF MDI 28.8/9.6 ug | -0.0001 | 0.0034 | 0.0043 | -0.040 | -0.0110 | 0.0034 |
| GP MDI 28.8 ug | -0.0013 | 0.0046 | -0.0010 | -0.043 | -0.0018 | -0.0006 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (NCT02196714)
Timeframe: Day 1
| Intervention | 1/h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 0.1506 |
| GFF MDI 14.4/9.6 ug | 0.1983 |
| GP MDI 28.8 ug | 0.1100 |
| GP MDI 14.4 ug | 0.1614 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (T 1/2) (NCT02196714)
Timeframe: Day 1
| Intervention | h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 5.45 |
| GFF MDI 14.4/9.6 ug | 5.25 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (T 1/2) (NCT02196714)
Timeframe: Day 1
| Intervention | h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 9.49 |
| GFF MDI 14.4/9.6 ug | 4.14 |
| GP MDI 28.8 ug | 24.87 |
| GP MDI 14.4 ug | 19.13 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (tmax) (NCT02196714)
Timeframe: Day 1
| Intervention | h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 0.10 |
| GFF MDI 14.4/9.6 ug | 0.10 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (tmax) (NCT02196714)
Timeframe: Day 1
| Intervention | h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 0.10 |
| GFF MDI 14.4/9.6 ug | 0.10 |
| GP MDI 28.8 ug | 0.10 |
| GP MDI 14.4 ug | 0.10 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (NCT02196714)
Timeframe: Day 1
| Intervention | L (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 1187.75 |
| GFF MDI 14.4/9.6 ug | 1054.16 |
Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrroniuml by Treatment (NCT02196714)
Timeframe: Day 1
| Intervention | L (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 3508.00 |
| GFF MDI 14.4/9.6 ug | 2577.78 |
| GP MDI 28.8 µg | 3555.88 |
| GP MDI 14.4 µg | 2101.03 |
Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 hours
| Intervention | g/L (Mean) | |
|---|---|---|
| Albumin (g/L) | Protein (g/L) | |
| GFF MDI 14.4/9.6 ug | -6.9 | -10.8 |
| GFF MDI 28.8/9.6 ug | -7.1 | -10.9 |
| GP MDI 28.8 ug | -6.7 | -10.3 |
Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 hours
| Intervention | IU/L (Mean) | |||
|---|---|---|---|---|
| ALT (IU/L) | Alkaline phosphatase (IU/L) | AST (IU/L) | Gamma glutamyl transferase (IU/L) | |
| GFF MDI 14.4/9.6 ug | -1.7 | -5.0 | -3.3 | -1.6 |
| GFF MDI 28.8/9.6 ug | -3.1 | -5.2 | -4.2 | -2.5 |
| GP MDI 28.8 ug | -2.4 | -6.0 | -3.7 | -2.2 |
Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 hours
| Intervention | μmol/L (Mean) | |||
|---|---|---|---|---|
| Creatinine (μmol/L) | Direct bilirubin (μmol/L) | Iron (μmol/L) | Total bilirubin (μmol/L) | |
| GFF MDI 14.4/9.6 ug | 4.92 | -2.53 | -2.81888 | -7.14 |
| GFF MDI 28.8/9.6 ug | 1.88 | -3.06 | -5.42524 | -8.19 |
| GP MDI 28.8 ug | 3.61 | -2.64 | -2.58949 | -7.20 |
Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 hours
| Intervention | mmol/L (Mean) | |||||
|---|---|---|---|---|---|---|
| Blood urea nitrogen (mmol/L) | Calcium (mmol/L) | Chloride (mmol/L) | Magnesium (mmol/L) | Phosphorus (mmol/L) | Sodium (mmol/L) | |
| GFF MDI 14.4/9.6 ug | 0.34 | -0.14 | 2.5 | -0.07 | 0.163 | 0.5 |
| GFF MDI 28.8/9.6 ug | 0.01 | -0.15 | 3.0 | -0.05 | 0.135 | 0.9 |
| GP MDI 28.8 ug | 0.74 | -0.13 | 2.3 | -0.04 | 0.133 | 0.1 |
Change in Mean Glucose and Potassium Results (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 hours
| Intervention | mmol/L (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Glucose (mmol/L) 30 minutes post-dose | Glucose (mmol/L) 2 hours post-dose | Glucose (mmol/L) 4 hours post-dose | Glucose (mmol/L) 12 hours post-dose | Potassium (mmol/L) 30 minutes post-dose | Potassium (mmol/L) 2 hours post-dose | Potassium (mmol/L) 4 hours post-dose | Potassium (mmol/L) 12 hours post-dose | |
| GFF MDI 14.4/9.6 ug | -0.08 | -0.01 | -0.24 | 0.18 | 0.00 | -0.07 | -0.12 | -0.06 |
| GFF MDI 28.8/9.6 ug | -0.03 | 0.05 | -0.08 | 0.10 | 0.01 | -0.02 | -0.01 | 0.05 |
| GP MDI 28.8 ug | -0.01 | -0.06 | -0.16 | 0.23 | 0.06 | 0.10 | -0.07 | 0.07 |
Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 Hours
| Intervention | g/L (Mean) | |
|---|---|---|
| Ery. mean corpuscuar HGB (g/L) | Hemoglobin (g/L) | |
| GFF MDI 14.4/9.6 ug | 8.5 | -10.61 |
| GFF MDI 28.8/9.6 ug | 12.0 | -8.81 |
| GP MDI 28.8 ug | 11.4 | -10.38 |
Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (NCT02196714)
Timeframe: 12 Hours
| Intervention | 10^9cells/L (Mean) | ||||||
|---|---|---|---|---|---|---|---|
| Basophils (10^9cells/L) | Eosinophils (10^9cells/L) | Granulocytes (10^9cells/L) | Leukocytes (10^9cells/L) | Lymphocytes (10^9cells/L) | Monocytes (10^9cells/L) | Platelets (10^9cells/L) | |
| GFF MDI 14.4/9.6 ug | 0.000 | 0.033 | 0.483 | 0.780 | 0.206 | 0.056 | -14.4 |
| GFF MDI 28.8/9.6 ug | 0.007 | 0.044 | 0.222 | 0.484 | 0.147 | 0.065 | -22.4 |
| GP MDI 28.8 ug | 0.001 | 0.065 | 0.443 | 0.800 | 0.235 | 0.055 | -23.1 |
Change in QTc Bazett Interval from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | msec (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 7.2 |
| GFF MDI 14.4/9.6 ug | 4.4 |
| GP MDI 28.8 ug | -5.8 |
Change in QT Interval from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | msec (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -28.5 |
| GFF MDI 14.4/9.6 ug | -24.8 |
| GP MDI 28.8 ug | -20.5 |
Change in QRS duration from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | msec (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -3.9 |
| GFF MDI 14.4/9.6 ug | -1.1 |
| GP MDI 28.8 ug | -4.0 |
Change in QRS axis from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | QRS axis (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -0.5 |
| GFF MDI 14.4/9.6 ug | 4.1 |
| GP MDI 28.8 ug | 0.0 |
Change in PR Interval from Pre-dose to 12 hours Post dose (NCT02196714)
Timeframe: 12 hours
| Intervention | msec (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -10.7 |
| GFF MDI 14.4/9.6 ug | -8.5 |
| GP MDI 28.8 ug | -7.4 |
Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Erythrocytes) (NCT02196714)
Timeframe: 12 Hours
| Intervention | 10^12cells/L (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -0.391 |
| GFF MDI 14.4/9.6 ug | -0.419 |
| GP MDI 28.8 ug | -0.433 |
Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Ery. mean corpuscuar volume) (NCT02196714)
Timeframe: 12 Hours
| Intervention | fL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -0.9 |
| GFF MDI 14.4/9.6 ug | -0.8 |
| GP MDI 28.8 ug | -0.9 |
Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Ery. mean corpuscuar hemoglobin) (NCT02196714)
Timeframe: 12 Hours
| Intervention | pg/cell (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 0.78 |
| GFF MDI 14.4/9.6 ug | 0.49 |
| GP MDI 28.8 ug | 0.75 |
Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Ferritin) (NCT02196714)
Timeframe: 12 hours
| Intervention | μg/L (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -14.169 |
| GFF MDI 14.4/9.6 ug | -11.949 |
| GP MDI 28.8 ug | -11.669 |
Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (eGFR) (NCT02196714)
Timeframe: 12 hours
| Intervention | mL/min/1.73m2 (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | -4.2 |
| GFF MDI 14.4/9.6 ug | -7.2 |
| GP MDI 28.8 ug | -3.5 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (AUC 0-∞) (NCT02196714)
Timeframe: Day 1
| Intervention | h*pg/mL (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 61.88 |
| GFF MDI 14.4/9.6 ug | 61.43 |
Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (NCT02196714)
Timeframe: Day 1
| Intervention | L/h (Mean) |
|---|---|
| GFF MDI 28.8/9.6 ug | 168.95 |
| GFF MDI 14.4/9.6 ug | 161.55 |
A severe exacerbation is defined as a deterioration of asthma requiring any of the following: use of systemic glucocorticosteroids (GCS) for at least 3 days, inpatient hospitalization, or emergency room visit due to asthma that required systemic steroids. (NCT02224157)
Timeframe: Day 1 up to 52 weeks
| Intervention | Participants (Number) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 177 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 184 |
'As needed' free days (%) change from baseline during randomised treatment period. An 'as-needed' free day was defined as a day and night with no use of 'as needed' medication. Variable analysed is the percentage (%) of 'as-needed' free days during the randomised treatment period. Baseline is defined by the last 10 days of the run-in period. (NCT02224157)
Timeframe: Week 0 up to 52 weeks
| Intervention | Percentage of 'as needed' free days (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 41.01 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 47.86 |
The average change from baseline (baseline defined by measurement at week 0, prior to first dose of IP) to the treatment period average assessed over the entire treatment period in pre-bronchodilator FEV1 was derived by computing a contrast for the mean across the post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis. (NCT02224157)
Timeframe: Study weeks 0,17, 34, 52
| Intervention | mL (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 104.0 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 136.6 |
AQLQ(S) consists of 32 questions in 4 domains. Each question is assessed on a 7-point scale from 1 to 7, with higher values indicating better health-related quality of life. The overall score is calculated as the mean score of all 32 items. The average change from baseline to treatment period average in AQLQ(S) overall score was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis. (NCT02224157)
Timeframe: Study weeks 0,17, 34, 52
| Intervention | AQLQ(S) overall score (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 0.335 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 0.431 |
ACQ questionnaire contains five questions on patients' symptoms, which are assessed on a 7-point scale from 0 (representing good control) to 6 (representing poor control). The score is the mean score of all questions for which responses are provided. The average change from baseline to treatment period average in ACQ-5 was derived by computing a contrast for the mean across all post-randomisation visits (week 17, 34, 52) from the MMRM (mixed model repeated measures) analysis. (NCT02224157)
Timeframe: Study weeks 0, 17, 34, 52
| Intervention | Score (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | -0.35 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | -0.46 |
The following two criteria lead to discontinuation from the IP due to asthma related events: A severe asthma exacerbation with duration for more than 3 weeks, and/or three severe asthma exacerbations during 6 months. (NCT02224157)
Timeframe: Day 1 up to 52 weeks
| Intervention | Participants (Number) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 0 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 4 |
Severe asthma exacerbations over the randomised treatment period, negative binomial model for non-inferiority test evaluation (NCT02224157)
Timeframe: up to 52 weeks
| Intervention | exacerbations per participant year (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 0.11 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 0.12 |
Severe asthma exacerbations over the randomised treatment period, negative binomial model for superiority test evaluation (NCT02224157)
Timeframe: up to 52 weeks
| Intervention | exacerbations per participant year (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 0.11 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 0.12 |
'As-needed' use change from baseline over the randomised treatment period. Baseline was defined as the last 10 days of the run-in period. 'As needed' use was calculated as the cumulative doses of 'as-needed' medication over the randomised treatment period divided by the follow-up time (number of days - 1). ie, average number of inhalations per day. (NCT02224157)
Timeframe: Week 0 up to 52 weeks
| Intervention | Number of inhalations per day (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | -0.84 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | -0.87 |
ICS controller use days (%) during the randomised treatment period is calculated as the cumulative days when any controller medication (containing ICS) was taken including maintenance (Pulmicort bid group) and 'as needed' medication (Symbicort 'as needed' group) and additional prescribed ICS for asthma (all treatment groups), divided by the number of days in the randomised treatment period. (NCT02224157)
Timeframe: Week 0 up to 52 weeks
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| Placebo Bid + Symbicort 'as Needed' (Experimental) | 30.45 |
| Pulmicort Bid + Terbutaline 'as Needed' (Active Comparator) | 67.92 |
"Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.08 |
| Treatment B | 0.08 |
| Treatment C | 0.08 |
| Treatment D | 0.08 |
"Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 47.4 |
| Treatment B | 40.1 |
| Treatment C | 44.7 |
| Treatment D | 34.5 |
"Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.08 |
| Treatment B | 0.25 |
| Treatment C | 0.08 |
| Treatment D | 0.25 |
"Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 9.57 |
| Treatment B | 9.33 |
| Treatment C | 10.09 |
| Treatment D | 9.15 |
"Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 2.90 |
| Treatment B | 2.94 |
| Treatment C | 2.79 |
| Treatment D | 2.80 |
Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 1040 |
| Treatment B | 482 |
| Treatment C | 1090 |
| Treatment D | 542 |
"Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1980 |
| Treatment B | 1450 |
| Treatment C | 1900 |
| Treatment D | 1410 |
"FVC = Forced vital capacity. It is the full amount of air that can be exhaled with effort in a complete breath.~FEV1/FVC = Tiffenau-Pinelli Index. This parameter represents the measurement of the amount of air an individual can forcefully exhale from his/her lungs.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.~Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together.~But 6 subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174." (NCT02237508)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | ratio (Mean) |
|---|---|
| Treatment A | 3.7 |
| Treatment B | 3.6 |
| Treatment C | 3.2 |
| Treatment D | 3.8 |
"PEFR is the highest rate at which gases can be expelled from the lungs via an open mouth. Its measurement is a simple procedure in which an individual takes a full inspiration and blows out as forcibly as possible into an instrument called a peak flow meter, which measures the maximal gas flow in an exhalation in liters per minute.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together. But 6 subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174." (NCT02237508)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | L/min (Mean) |
|---|---|
| Treatment A | 22.2 |
| Treatment B | 20.5 |
| Treatment C | 24.8 |
| Treatment D | 19.2 |
"FEV1 refers to the volume of air that an individual can exhale during a forced breath in 1 second.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.~and Symbicort 2, together. Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together.~But some subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174." (NCT02237508)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | liters (Mean) |
|---|---|
| Treatment A | 0.2 |
| Treatment B | 0.2 |
| Treatment C | 0.2 |
| Treatment D | 0.2 |
"Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 56.0 |
| Treatment B | 49.8 |
| Treatment C | 54.5 |
| Treatment D | 45.2 |
"Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 324 |
| Treatment B | 174 |
| Treatment C | 342 |
| Treatment D | 193 |
"Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Least Squares Mean) |
|---|---|
| Treatment A | 3.85 |
| Treatment B | 3.12 |
| Treatment C | 4.00 |
| Treatment D | 3.35 |
"Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule.~Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1870 |
| Treatment B | 1360 |
| Treatment C | 1810 |
| Treatment D | 1330 |
Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02237508)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 11.9 |
| Treatment B | 9.53 |
| Treatment C | 12.4 |
| Treatment D | 10.6 |
Percentage of Correct Advances (±2 or ±4 Actuations) of the Dose Indicator Based on Subject-reported Actuation Count (NCT02268396)
Timeframe: Over the life of the canister/120 puffs - up to 4 weeks
| Intervention | Percentage of correct advances (Number) | |
|---|---|---|
| Correct within ±2 actuations | Correct within ±4 actuations | |
| GFF MDI (PT003) | 87.3 | 93.2 |
Dose Indicator Actuation Consistency: Percentage of Devices in Agreement Between CRF-Based Dose Indicator Actuation Count and Subject-Reported Actuation Count at the Last Available Visit: ITT Population (NCT02268396)
Timeframe: Over the life of the canister/120 puffs - up to 4 weeks
| Intervention | Percentage (Number) |
|---|---|
| GFF MDI (PT003) | 96.4 |
Percentage of devices whose number of actuations counted at the end of the study, using the dose indicator reading, was consistent (±20 actuations) with the number of actuations used as estimated by the change in MDI weight (NCT02268396)
Timeframe: Over the life of the canister/120 puffs - up to 4 weeks
| Intervention | Percentage of Devices (Number) |
|---|---|
| GFF MDI (PT003) | 86.9 |
Percentage of devices whose number of actuations counted at the end of the study, using the dose indicator reading, was consistent (±20 actuations) with the number of actuations used as estimated by the change in MDI weight (NCT02268396)
Timeframe: Over the life of the canister/120 puffs - up to 4 weeks
| Intervention | Percentage (Number) |
|---|---|
| GFF MDI (PT003) | 75.0 |
Percentage of devices whose number of actuations counted at the end of the study, using the lab-advanced dose indicator reading, was consistent (±20 actuations) with the number of actuations used as reported by the subject (NCT02268396)
Timeframe: Over the life of the canister/120 puffs - up to 4 weeks
| Intervention | Percentage of devices (Number) |
|---|---|
| GFF MDI (PT003) | 96.2 |
Percentage of devices where the dose indicator actuation count is >20 less than the subject-reported actuation count (undercount) (NCT02268396)
Timeframe: Over the life of the canister/120 puffs - up to 4 weeks
| Intervention | Percentage (Number) |
|---|---|
| GFF MDI (PT003) | 2.9 |
"Change in FEV1 from Baseline through 4 hours post formoterol dose. This was completed at visit 1 and visit 2.~Steps:~A baseline (pre-dose formoterol) FEV1 was recorded.~Subjects were dosed with formoterol.~Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FEV1 values were recorded.~A percentage of change from baseline FEV1 to each serial measurement of FEV1 was collected. The % of change at each time point was then used to get a measure of overall percentage change of the predicted FEV1 value." (NCT02291016)
Timeframe: Baseline through study completion (visit 1 through visit 2)
| Intervention | percentage change of % predicted FEV1 (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 21.5 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 18.4 |
"A baseline (pre-dose formoterol) FVC was recorded.~Subjects were dosed with formoterol.~Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded.~A percentage of change between the baseline and peak FVC will be recorded for this outcome measure." (NCT02291016)
Timeframe: Measured at visit 1 and again at the end of visit 2
| Intervention | percent change (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 22.1 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 18.2 |
"Steps:~A baseline (pre-dose formoterol) FVC was recorded.~Subjects were dosed with formoterol.~Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded.~Peak FVC was recorded for this outcome measure and compared amongst groups." (NCT02291016)
Timeframe: Peak FVC at visit 1 will be compared to the peak FVC at visit 2 for any significant change.
| Intervention | L/sec (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 86.7 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 82.0 |
"Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2.~Steps:~A baseline (pre-dose formoterol) FEV1 was recorded.~Subjects were dosed with formoterol.~Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement could recorded.~5. Peak measurements from visit 1 and visit 2 will be compared for any significant change in FEV1 values." (NCT02291016)
Timeframe: Measured from Start of visit 1 until the completion of visit 2
| Intervention | L/sec (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 12.2 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 9.5 |
The Shortness of Breath Modified Borg Dyspnea Scale The scale goes from 0-10, zero meaning no difficulty breathing and ten meaning maximal difficulty. A decrease of score indicates an improvement. Patients were asked to complete the scale pre-dose and again one hour post formoterol dose. This was completed at both visit 1 and visit 2. The value recorded was the difference between the baseline value and the post 60 minute value. (NCT02291016)
Timeframe: Measured at visit 1 and again at the end of visit 2
| Intervention | change in score (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | -0.59 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 0 |
"Steps:~A baseline (pre-dose formoterol) FVC was recorded.~Subjects were dosed with formoterol.~Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded.~Data was all time points were used to obtain the total area under the curve" (NCT02291016)
Timeframe: Measured at visit 1 and again at the end of visit 2
| Intervention | mcg*hr/mL (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 327.0 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 293.4 |
"Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2.~Steps:~A baseline (pre-dose formoterol) FEV1 will be recorded.~Subjects will be dosed with formoterol.~Serial FEV1 assessments will completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement can be recorded.~A percentage of change between the baseline and peak FEV1 will be recorded for this outcome measure. A higher value indicates a better result." (NCT02291016)
Timeframe: From pre-dose formoterol (baseline 0hrs) to 30 minutes, 1,2, and 4 hours post dose at visit 1 and measured again at visit 2
| Intervention | percent change (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 28.2 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 21.1 |
"Increase in FEV1 from Baseline to 4 hours post dose of formoterol. This will be completed at visit 1 and visit 2.~Steps:~A baseline (pre-dose formoterol) FEV1 was recorded.~Subjects was dosed with formoterol.~Serial FEV1 assessments were completed, and recorded at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so serial FEV1 measurements could be recorded." (NCT02291016)
Timeframe: Measured at visit 1 and visit 2 after dosing and all FEV1 testing has been completed
| Intervention | L/sec (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 12.2 |
| Formoterol With Dry Powder Inhaler and Placebo With Nebulizer | 9.5 |
The difference between the values of area under the response curve for FEV1 from baseline through four hours (AUC FEV1 0-4h) after inhalation of formoterol with a nebulizer or a dry powder inhaler. (NCT02291016)
Timeframe: Baseline through study completion (visit 1 through visit 2)
| Intervention | mcg*hr/mL (Mean) |
|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 203.0 |
| Formoterol With Dry Powder Inhaler | 185.0 |
Onset of Action as Assessed by FEV1 Day 1 at 5 Minutes Post-Dose. Reported is the FEV1 measured at 5 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant (NCT02343458)
Timeframe: Assessed at 5-minutes post dose on Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 0.202 |
| FF MDI 9.6 ug | 0.186 |
| GP MDI 14.4 ug | 0.059 |
| Placebo MDI | 0.022 |
Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks EU/SK/TW approach (NCT02343458)
Timeframe: over 24 weeks
| Intervention | mL (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 375 |
| FF MDI 9.6 ug | 277 |
| GP MDI 14.4 ug | 234 |
| Placebo MDI | 82 |
Onset of Action as Assessed by FEV1 Day 1 at 15 Minutes Post-Dose. Reported is the FEV1 measured at 15 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant (NCT02343458)
Timeframe: Assessed at 15-minute post dose on Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 0.241 |
| FF MDI 9.6 ug | 0.220 |
| GP MDI 14.4 ug | 0.105 |
| Placebo MDI | 0.033 |
TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 (NCT02343458)
Timeframe: over 24 Weeks
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 1.5 |
| FF MDI 9.6 ug | 1.3 |
| GP MDI 14.4 ug | 1.1 |
| Placebo MDI | 0.7 |
TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 (NCT02343458)
Timeframe: over 24 Weeks
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 1.6 |
| FF MDI 9.6 ug | 1.5 |
| GP MDI 14.4 ug | 1.3 |
| Placebo MDI | 0.8 |
TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 (NCT02343458)
Timeframe: over Weeks 12-24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 1.7 |
| FF MDI 9.6 ug | 1.5 |
| GP MDI 14.4 ug | 1.4 |
| Placebo MDI | 0.8 |
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life (NCT02343458)
Timeframe: over weeks 12-24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | -6.9 |
| FF MDI 9.6 ug | -7.3 |
| GP MDI 14.4 ug | -3.9 |
| Placebo MDI | -3.1 |
Change from baseline in morning pre-dose trough FEV1 over weeks 12-24, Japan approach (NCT02343458)
Timeframe: over weeks 12-24
| Intervention | mL (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 128 |
| FF MDI 9.6 ug | 54 |
| GP MDI 14.4 ug | 74 |
| Placebo MDI | -25 |
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life (NCT02343458)
Timeframe: over weeks 12-24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | -5.2 |
| FF MDI 9.6 ug | -5.0 |
| GP MDI 14.4 ug | -3.6 |
| Placebo MDI | -1.7 |
Peak change from baseline in FEV1 within 2 hours post-dosing over weeks 12-24 Japan approach (NCT02343458)
Timeframe: over weeks 12-24
| Intervention | mL (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 368 |
| FF MDI 9.6 ug | 255 |
| GP MDI 14.4 ug | 228 |
| Placebo MDI | 70 |
Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 US/China approach (NCT02343458)
Timeframe: at week 24
| Intervention | mL (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 358 |
| FF MDI 9.6 ug | 247 |
| GP MDI 14.4 ug | 214 |
| Placebo MDI | 55 |
Change from baseline in average daily rescue Ventolin use over 24 weeks in RVU population, all approaches (NCT02343458)
Timeframe: over 24 weeks
| Intervention | Puffs/day (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | -1.4 |
| FF MDI 9.6 ug | -1.0 |
| GP MDI 14.4 ug | -0.6 |
| Placebo MDI | -0.4 |
For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment (NCT02343458)
Timeframe: at week 24
| Intervention | mL (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 120 |
| FF MDI 9.6 ug | 47 |
| GP MDI 14.4 ug | 60 |
| Placebo MDI | -45 |
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life (NCT02343458)
Timeframe: at week 24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | -5.3 |
| FF MDI 9.6 ug | -5.6 |
| GP MDI 14.4 ug | -3.7 |
| Placebo MDI | -0.9 |
Change from baseline in morning pre-dose trough FEV1 over 24 weeks. Primary endpoint, EU/SK/TW approach, Secondary endpoint US/China approach. (NCT02343458)
Timeframe: over 24 weeks
| Intervention | mL (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 135 |
| FF MDI 9.6 ug | 63 |
| GP MDI 14.4 ug | 80 |
| Placebo MDI | -20 |
Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life (NCT02343458)
Timeframe: at week 24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | -6.9 |
| FF MDI 9.6 ug | -7.8 |
| GP MDI 14.4 ug | -3.8 |
| Placebo MDI | -1.6 |
TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9 (NCT02343458)
Timeframe: over weeks 12-24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| GFF MDI 14.4/9.6 ug | 1.5 |
| FF MDI 9.6 ug | 1.4 |
| GP MDI 14.4 ug | 1.1 |
| Placebo MDI | 0.7 |
Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12 and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | International units per liter (IU/L) (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Week 24, ALT, n=838,785 | Maximum post BL, ALT, n=887,864 | Week 24, AST, n=835,785 | Maximum post BL, AST, n=887,866 | Week 24, ALP, n=839,787 | Maximum post BL, ALP, n=888,866 | Week 24, GGT, n=839,787 | Maximum post BL, GGT, n=888,866 | Week 24, Creatine Kinase, n=839,787 | Maximum post BL, Creatine Kinase, n=888,866 | |
| BUD/FOR 400/12 µg | 3.8 | 5.5 | 4.0 | 5.6 | -2.8 | 0.8 | 0.5 | 4.7 | -3.4 | 20.6 |
| FF/UMEC/VI 100/62.5/25 µg | 1.4 | 3.0 | 1.1 | 3.2 | 1.1 | 4.3 | 3.4 | 7.5 | -3.9 | 20.6 |
Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12 and Week 24. Change from Baseline (BL) was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). The maximum post BL values have been presented. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | g/L (Mean) | |||
|---|---|---|---|---|
| Week 24, Albumin, n=839,787 | Maximum post BL, Albumin, n=888,866 | Week 24, Protein, n=839,787 | Maximum post BL, Protein, n=888,866 | |
| BUD/FOR 400/12 µg | -0.5 | 0.2 | -1.0 | 0.1 |
| FF/UMEC/VI 100/62.5/25 µg | -0.7 | 0.1 | -0.6 | 0.4 |
Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | g/L (Mean) | |||
|---|---|---|---|---|
| Week 52, Albumin, n=181,174 | Maximum post BL,Albumin, n=207,214 | Week 52, Protein, n=181,174 | Maximum post BL, Protein, n=207,214 | |
| BUD/FOR 400/12 µg | -0.7 | 0.2 | -1.6 | 0.0 |
| FF/UMEC/VI 100/62.5/25 µg | -0.8 | 0.4 | -1.1 | 0.6 |
Hematology laboratory assessments included basophils, eosinophils, lymphocytes, monocytes, neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a repeat test). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | 10^9 cells/Liter(L) (Mean) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 24, Basophils, n=817,761 | Maximum post BL, Basophils, n=876,853 | Week 24, Eosinophils, n=817, 761 | Maxmium post BL, Eosinophils, n=876,853 | Category title 5. Week 24, Monocytes, n=817,761 | Maximum post BL, Monocytes, n=876,853 | Week 24, Neutrophils, n=817,761 | Maximum post BL, Neutrophils, n=876,853 | Week 24, Leukocytes, n=819,761 | Maximum post BL, Leukocytes, n=877,853 | Week 24, Platelets, n=810,759 | Maximum post BL, Platelets, n=871,846 | Week 24, Lymphocytes, n=817,761 | Maximum post BL, Lymphocytes, n=876,853 | |
| BUD/FOR 400/12 µg | -0.001 | 0.005 | -0.015 | 0.019 | 0.004 | 0.048 | 0.142 | 0.649 | 0.11 | 0.64 | -0.7 | 10.2 | -0.023 | 0.150 |
| FF/UMEC/VI 100/62.5/25 µg | -0.001 | 0.005 | -0.008 | 0.034 | -0.006 | 0.040 | 0.071 | 0.481 | 0.06 | 0.52 | -0.7 | 10.8 | 0.002 | 0.187 |
Hematology laboratory assessments included Basophils, eosinophils, lymphocytes, monocytes,neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | 10^9 cells/L (Mean) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 52, Basophils, n=168,166 | Maximum post BL, Basophils, n=205,212 | Week 52, Eosinophils, n=168,166 | Maximum post BL, Eosinophils, n=205,212 | Week 52, Monocytes, n=168,166 | Maximum post BL, Monocytes, n=205,212 | Week 52, Neutrophils, n=168,166 | Maximum post BL, Neutrophils, n=205,212 | Week 52, Leukocytes, n=168,166 | Maximum post BL, Leukocytes, n=205,212 | Week 52, Platelets, n=170,166 | Maximum post BL, Platelets, n=203,210 | Week 52, Lymphocytes, n=168,166 | Maximum post BL, Lymphocytes, n=202,212 | |
| BUD/FOR 400/12 µg | 0.003 | 0.010 | -0.011 | 0.057 | 0.028 | 0.072 | -0.163 | 0.835 | -0.17 | 0.87 | -2.7 | 13.9 | -0.027 | 0.295 |
| FF/UMEC/VI 100/62.5/25 µg | 0.002 | 0.011 | 0.002 | 0.074 | 0.025 | 0.075 | 0.246 | 0.923 | 0.33 | 0.97 | -1.8 | 13.6 | 0.060 | 0.325 |
Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Micromoles per liter (Mean) | |||||
|---|---|---|---|---|---|---|
| Week 24, Bilirubin, n=839,786 | Maximum post BL, Bilirubin, n=888,865 | Week 24, Creatinine, n=839,787 | Maximum post BL, Creatinine, n=888,866 | Week 24, Urate, n=839,787 | Maximum post BL, Urate, n=888,866 | |
| BUD/FOR 400/12 µg | 0.1 | 1.2 | 1.14 | 3.99 | 1.7 | 21.9 |
| FF/UMEC/VI 100/62.5/25 µg | -0.2 | 1.1 | 1.05 | 4.12 | 2.8 | 23.7 |
Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, Week 24, and Week 52 of the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Micromoles per liter (Mean) | |||||
|---|---|---|---|---|---|---|
| Week 52, Bilirubin, n=181,174 | Maximum post BL, Bilirubin, n=207,214 | Week 52, Creatinine, n=181,174 | Maximum post BL, Creatinine, n=207,214 | Week 52, Urate, n=181,174 | Maximum post BL, Urate, n=207,214 | |
| BUD/FOR 400/12 µg | 0.1 | 2.3 | 1.28 | 6.00 | 3.9 | 40.0 |
| FF/UMEC/VI 100/62.5/25 µg | 0.3 | 2.0 | 2.95 | 6.99 | 3.6 | 42.0 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Milliseconds (msec) (Least Squares Mean) | |
|---|---|---|
| QTcF, n=840,787 | PR, n=812,766 | |
| BUD/FOR 400/12 µg | 0.6 | 0.5 |
| FF/UMEC/VI 100/62.5/25 µg | 2.5 | -0.1 |
Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | 10^12 cells/L (Mean) | |
|---|---|---|
| Week 24, n=822,769 | Maximum post BL, n=880,857 | |
| BUD/FOR 400/12 µg | -0.04 | 0.04 |
| FF/UMEC/VI 100/62.5/25 µg | -0.02 | 0.06 |
Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | 10^12 cells/L (Mean) | |
|---|---|---|
| Week 52, n=174,170 | Maximum post BL, n=206,212 | |
| BUD/FOR 400/12 µg | 0.00 | 0.07 |
| FF/UMEC/VI 100/62.5/25 µg | 0.02 | 0.11 |
Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, phophate, potassium, sodium, and urea at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Millimoles per liter (mmol/L) (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 24, Calcium, n=835,785 | Maximum post BL, Calcium, n=887,866 | Week 24, Chloride, n=838,787 | Maximum post BL, Chloride, n=888,866 | Week 24, CO2, n=835,785 | Maximum post BL, CO2, n=835,785 | Week 24, Glucose, n=839,787 | Maximum post BL, Glucose, n=887,866 | Week 24, Potassium, n=834,785 | Maximum post BL, Potassium, n=887,866 | Week 24, Phosphate, n=839,787 | Maximum post BL, Phosphate, n=888,866 | Week 24, Sodium, n=837,787 | Maximum post BL, Sodium, n=888,866 | Week 24, Urea, n=839,787 | Maximum post BL, Urea, n=888,866 | |
| BUD/FOR 400/12 µg | -0.014 | 0.012 | -0.7 | 0.6 | -0.0 | 0.5 | -0.00 | 0.37 | -0.03 | 0.13 | -0.029 | 0.043 | -0.2 | 0.7 | 0.04 | 0.64 |
| FF/UMEC/VI 100/62.5/25 µg | -0.016 | 0.013 | -0.4 | 0.9 | -0.6 | 0.0 | 0.12 | 0.53 | 0.04 | 0.18 | -0.028 | 0.039 | -0.3 | 0.6 | 0.08 | 0.68 |
Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, magnesium, phophate, potassium, sodium, and urea at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Mmol/L (Mean) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 52, Calcium, n=180,174 | Maximum post BL,Calcium, n=207,214 | Week 52, Chloride, n=181,174 | Maximum post BL,Chloride, n=207,214 | Week 52, CO2, n=180,174 | Maximum post BL,CO2, n=207,214 | Week 52, Glucose, n=181,174 | Maximum post BL,Glucose, n=207,214 | Week 52, Potassium, n=180,174 | Maximum post BL,Potassium, n=207,214 | Week 52, Phosphate, n=181,174 | Maximum post BL,Phosphate, n=207,214 | Week 52, Sodium, n=181,174 | Maximum post BL,Sodium, n=207,214 | Week 52, Urea, n=181,174 | Maximum post BL, Urea, n=207,214 | |
| BUD/FOR 400/12 µg | -0.040 | 0.008 | -0.2 | 1.3 | -1.0 | 0.3 | 0.22 | 0.63 | -0.10 | 0.20 | 0.005 | 0.110 | -0.1 | 1.1 | 0.12 | 1.08 |
| FF/UMEC/VI 100/62.5/25 µg | -0.033 | 0.026 | -0.1 | 1.4 | -1.2 | -0.2 | 0.31 | 0.92 | -0.02 | 0.29 | -0.003 | 0.109 | -0.2 | 1.1 | 0.16 | 1.06 |
Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Fraction of 1 (Mean) | |
|---|---|---|
| Week 24, n=822,769 | Maximum post BL, n=880,857 | |
| BUD/FOR 400/12 µg | 0.0024 | 0.0123 |
| FF/UMEC/VI 100/62.5/25 µg | 0.0024 | 0.0115 |
Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as Most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Fraction of 1 (Mean) | |
|---|---|---|
| Week 52, n=174,170 | Maximum post BL, n=206,212 | |
| BUD/FOR 400/12 µg | -0.0056 | 0.0149 |
| FF/UMEC/VI 100/62.5/25 µg | -0.0056 | 0.0153 |
Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Grams per liter (g/L) (Mean) | |
|---|---|---|
| Week 24, n=822,769 | Maximum post BL, n=880,857 | |
| BUD/FOR 400/12 µg | -1.0 | 1.5 |
| FF/UMEC/VI 100/62.5/25 µg | -0.9 | 1.5 |
Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | g/L (Mean) | |
|---|---|---|
| Week 52, n=174,170 | Maximum post BL, n=206,212 | |
| BUD/FOR 400/12 µg | -2.5 | 1.9 |
| FF/UMEC/VI 100/62.5/25 µg | -2.5 | 2.2 |
Single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Msec (Least Squares Mean) | |
|---|---|---|
| QTcF, n=181,169 | PR, n=174,160 | |
| BUD/FOR 400/12 µg | 2.4 | 1.4 |
| FF/UMEC/VI 100/62.5/25 µg | 1.4 | 1.6 |
Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were collected taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Millimeter of mercury (mmHg) (Least Squares Mean) | |
|---|---|---|
| SBP | DBP | |
| BUD/FOR 400/12 µg | -1.1 | -0.5 |
| FF/UMEC/VI 100/62.5/25 µg | -1.0 | -0.3 |
Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 52 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | mmHg (Least Squares Mean) | |
|---|---|---|
| SBP | DBP | |
| BUD/FOR 400/12 µg | 0.3 | 0.4 |
| FF/UMEC/VI 100/62.5/25 µg | -1.3 | -0.4 |
Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, Candida infection, oral fungal infection, and oropharyngeal candidiasis were reported. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) | |||
|---|---|---|---|---|
| Oral candidiasis | Candida infection | Oral fungal infection | Oropharyngeal candidiasis | |
| BUD/FOR 400/12 µg | 4 | 4 | 3 | 0 |
| FF/UMEC/VI 100/62.5/25 µg | 2 | 1 | 2 | 2 |
Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, candida infection, oral fungal infection, and oropharyngeal candidiasis were reported. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) | |
|---|---|---|
| Candida infection | Oral fungal infection | |
| BUD/FOR 400/12 µg | 3 | 2 |
| FF/UMEC/VI 100/62.5/25 µg | 0 | 0 |
An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) | |
|---|---|---|
| Any AE | Any SAE | |
| BUD/FOR 400/12 µg | 339 | 51 |
| FF/UMEC/VI 100/62.5/25 µg | 354 | 49 |
An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) | |
|---|---|---|
| Any AE | Any SAE | |
| BUD/FOR 400/12 µg | 122 | 28 |
| FF/UMEC/VI 100/62.5/25 µg | 100 | 21 |
Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query [SMQ; myocardial infarction SMQ and other ischemic diseases]) and narrow MACE criteria (myocardial infarction [acute myocardial infarction]. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) | |
|---|---|---|
| Any MACE, Narrow definition | Any MACE, Broad definition | |
| BUD/FOR 400/12 µg | 7 | 11 |
| FF/UMEC/VI 100/62.5/25 µg | 4 | 12 |
Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query [SMQ; myocardial infarction SMQ and other ischemic diseases]) and narrow MACE criteria (myocardial infarction [acute myocardial infarction] (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) | |
|---|---|---|
| Any MACE, Narrow definition | Any MACE, Broad definition | |
| BUD/FOR 400/12 µg | 2 | 5 |
| FF/UMEC/VI 100/62.5/25 µg | 5 | 7 |
Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 52 were summarized and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Bpm (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.7 |
| BUD/FOR 400/12 µg | -1.9 |
Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12, Week 24 and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | International units per liter (IU/L) (Mean) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Week 52, ALT, n=181,173 | Maximum post BL, ALT, n=207,212 | Week 52, AST, n=180,174 | Maximum post BL, AST, n=207,214 | Week 52, ALP, n=181,174 | Maximum post BL, ALP, n=207,214 | Week 52, GGT, n=181,174 | Maximum post BL, GGT, n=207,214 | Week 52, Creatine Kinase, n=181,174 | Maximum post BL, Creatine Kinase, n=207,214 | |
| BUD/FOR 400/12 µg | 1.3 | 4.5 | 0.8 | 3.7 | -2.7 | 1.2 | 0.2 | 8.9 | 16.7 | 46.9 |
| FF/UMEC/VI 100/62.5/25 µg | 1.7 | 5.4 | 1.7 | 5.5 | 1.7 | 6.7 | 0.2 | 7.7 | 6.1 | 39.9 |
A single 12-lead electrocardiogram (ECG) and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Beats per minute (Bpm) (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -1.1 |
| BUD/FOR 400/12 µg | -1.2 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Bpm (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.2 |
| BUD/FOR 400/12 µg | -1.0 |
Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat). (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Bpm (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -0.5 |
| BUD/FOR 400/12 µg | -0.8 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 24
| Intervention | Msec (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 1.5 |
| BUD/FOR 400/12 µg | -0.7 |
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24, and Week 52 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 52. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. (NCT02345161)
Timeframe: Baseline and Week 52
| Intervention | Msec (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.9 |
| BUD/FOR 400/12 µg | 2.2 |
The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 24 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions (NCT02345161)
Timeframe: Baseline to Week 24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -6.6 |
| BUD/FOR 400/12 µg | -4.3 |
The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 52 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. (NCT02345161)
Timeframe: Baseline to Week 52
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | -4.6 |
| BUD/FOR 400/12 µg | -1.9 |
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. ITT Population comprised of all randomized subjects excluding those who were randomized in error. Only participants with analyzable data at the given time point were analyzed. (NCT02345161)
Timeframe: Baseline to Week 24
| Intervention | Liters (L) (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.142 |
| BUD/FOR 400/12 µg | -0.029 |
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 52 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. Extension Population: all participants in the ITT Population who were enrolled into the subset of participants with extension to 52 weeks. (NCT02345161)
Timeframe: Baseline to Week 52
| Intervention | Liters (L) (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.126 |
| BUD/FOR 400/12 µg | -0.053 |
Participants were asked to complete the daily activity question as part of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| FF/UMEC/VI (100 mcg/62.5 mcg/25 mcg) | 0.0 |
| Budesonide/Formoterol (400 mcg/12 mcg) | -0.1 |
Participants were asked to complete the daily activity question as aprt of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Percentage of days (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.0 |
| BUD/FOR 400/12 µg | 0.3 |
The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant [par.] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, >=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1). (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Exacerbations per participant per year (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.22 |
| BUD/FOR 400/12 µg | 0.34 |
The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant [par.] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, >=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1). (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Exacerbations per participant per year (Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0.20 |
| BUD/FOR 400/12 µg | 0.36 |
All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray AND at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature > 37.5 °C), Elevated WBC (>10,000/mm3 or >15 percent immature forms) orr Hypoxemia (HbO2 saturation <88 percent or at least 2 percent lower than Baseline value). (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 4 |
| BUD/FOR 400/12 µg | 4 |
All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray and at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature > 37.5 °C), Elevated white blood cells (WBC) (>10,000/millimeter [mm^3] or >15 percent immature forms) or Hypoxemia (hemoglobin/oxygen [HbO2] saturation <88 percent or at least 2 percent lower than Baseline value). (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 20 |
| BUD/FOR 400/12 µg | 7 |
The 24-hour holter measurements were obtained at Screening and 24 hours prior to Week 24 (Visits 1 and 6). The number of participants with clinically significant change (abnormal) were reported. Holter Monitoring Population: all participants in the ITT Population who had at least one holter monitoring evaluation. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) |
|---|---|
| Overall Study Arm | 180 |
| BUD/FOR 400/12 µg | 165 |
To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest. (NCT02345161)
Timeframe: Up to Week 52
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 0 |
| BUD/FOR 400/12 µg | 1 |
To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest. (NCT02345161)
Timeframe: Up to Week 24
| Intervention | Participants (Number) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 4 |
| BUD/FOR 400/12 µg | 6 |
The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Week 4 and Week 24. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions. (NCT02345161)
Timeframe: Week 24
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 2.29 |
| BUD/FOR 400/12 µg | 1.72 |
The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Weeks 4, 24 and 52. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions (NCT02345161)
Timeframe: Week 52
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg | 1.74 |
| BUD/FOR 400/12 µg | 1.39 |
The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). (NCT02345161)
Timeframe: Baseline to Week 24
| Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 1-4, n=870,859 | Week 5-8, n=851,830 | Week 9-12, n=841,813 | Week 13-16, n=831,802 | Week 17-20, n=828,788 | Week 21-24, n=825,783 | Breathlessness score, Week 1-4, n=870,859 | Breathlessness score, Week 5-8, n=851,830 | Breathlessness score, Week 9-12, n=841,813 | Breathlessness score, Week 13-16, n=831, 802 | Breathlessness score, Week 17-20, n=828,788 | Breathlessness score, Week 21-24, n=825,783 | Cough, sputum score, Week 1-4, n=870,859 | Cough, sputum score, Week 5-8, n=851,830 | Cough, sputum score, Week 9-12, n=841,813 | Cough, sputum score, Week 13-16, n=831,802 | Cough, sputum score, Week 17-20, n=828,788 | Cough, sputum score, Week 21-24, n=825,783 | Chest score, Week 1-4, n=870,859 | Chest score, Week 5-8, n=851,830 | Chest score, Week 9-12, n=841,813 | Chest score, Week 13-16, n=831,802 | Chest score, Week 17-20, n=828,788 | Chest score, Week 21-24, n=825,783 | |
| BUD/FOR 400/12 µg | -0.50 | -0.77 | -1.05 | -1.09 | -1.02 | -0.96 | -0.20 | -0.26 | -0.34 | -0.36 | -0.31 | -0.30 | -0.24 | -0.39 | -0.50 | -0.53 | -0.53 | -0.50 | -0.06 | -0.12 | -0.20 | -0.20 | -0.17 | -0.17 |
| FF/UMEC/VI 100/62.5/25 µg | -1.45 | -2.00 | -2.23 | -2.42 | -2.43 | -2.31 | -0.71 | -0.95 | -1.03 | -1.11 | -1.10 | -1.07 | -0.41 | -0.59 | -0.67 | -0.74 | -0.77 | -0.72 | -0.33 | -0.46 | -0.54 | -0.58 | -0.57 | -0.53 |
The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). (NCT02345161)
Timeframe: Baseline to Week 52
| Intervention | Scores on a scale (Least Squares Mean) | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Week 1-4, n=205, 213 | Week 5-8, n=203, 208 | Week 9-12, n=201, 206 | Week 13-16, n=201, 204 | Week 17-20, n=201, 199 | Week 21-24, n=202, 197 | Week 25-28, n=194, 186 | Week 29-32, n=192, 181 | Week 33-36, n=187, 180 | Week 37-40, n=185, 177 | Week 41-44, n=180, 174 | Week 45-48, n=180, 173 | EXACT-RS Scores, Week 49-52, n=179, 171 | Breathlessness scores, Week 1-4, n=205, 213 | Breathlessness scores, Week 5-8, n=203, 208 | Breathlessness scores, Week 9-12, n=201, 206 | Breathlessness scores, Week 13-16, n=201, 204 | Breathlessness scores, Week 17-20, n=201, 199 | Breathlessness scores, Week 21-24, n=202, 197 | Breathlessness scores, Week 25-28, n=194, 186 | Breathlessness scores, Week 29-32, n=192, 181 | Breathlessness scores, Week 33-36, n=187, 180 | Breathlessness scores, Week 37-40, n=185, 177 | Breathlessness scores, Week 41-44, n=180, 174 | Breathlessness scores, Week 45-48, n=180, 173 | Breathlessness scores, Week 49-52, n=179, 171 | Cough and sputum scores, Week 1-4, n=205, 213 | Cough and sputum scores, Week 5-8, n=203, 208 | Cough and sputum scores, Week 9-12, n=201, 206 | Cough and sputum scores, Week 13-16, n=201, 204 | Cough and sputum scores, Week 17-20, n=201, 199 | Cough and sputum scores, Week 21-24, n=202, 197 | Cough and sputum scores, Week 25-28, n=194, 186 | Cough and sputum scores, Week 29-32, n=192, 181 | Cough and sputum scores, Week 33-36, n=187, 180 | Cough and sputum scores, Week 37-40, n=185, 177 | Cough and sputum scores, Week 41-44, n=180, 174 | Cough and sputum scores, Week 45-48, n=180, 173 | Cough and sputum scores, Week 49-52, n=179, 171 | Chest scores, Week 1-4, n=205, 213 | Chest scores, Week 5-8, n=203, 208 | Chest scores, Week 9-12, n=201, 206 | Chest scores, Week 13-16, n=201, 204 | Chest scores, Week 17-20, n=201, 199 | Chest scores, Week 21-24, n=202, 197 | Chest scores, Week 25-28, n=194, 186 | Chest scores, Week 29-32, n=192, 181 | Chest scores, Week 33-36, n=187, 180 | Chest scores, Week 37-40, n=185, 177 | Chest scores, Week 41-44, n=180, 174 | Chest scores, Week 45-48, n=180, 173 | Chest scores, Week 49-52, n=179, 171 | |
| BUD/FOR 400/12 µg | -0.72 | -0.90 | -1.21 | -1.52 | -1.53 | -1.52 | -1.16 | -0.90 | -0.62 | -1.11 | -0.81 | -0.64 | -0.61 | -0.31 | -0.32 | -0.44 | -0.57 | -0.50 | -0.50 | -0.38 | -0.26 | -0.14 | -0.37 | -0.24 | -0.11 | -0.08 | -0.32 | -0.44 | -0.52 | -0.62 | -0.73 | -0.71 | -0.57 | -0.48 | -0.40 | -0.54 | -0.41 | -0.39 | -0.44 | -0.09 | -0.13 | -0.24 | -0.31 | -0.29 | -0.30 | -0.21 | -0.16 | -0.08 | -0.20 | -0.16 | -0.13 | -0.08 |
| FF/UMEC/VI 100/62.5/25 µg | -1.24 | -1.97 | -2.18 | -2.53 | -2.64 | -2.63 | -2.48 | -2.33 | -2.12 | -2.34 | -2.30 | -2.17 | -2.03 | -0.64 | -0.93 | -1.05 | -1.19 | -1.17 | -1.13 | -1.14 | -1.11 | -1.08 | -1.13 | -1.06 | -0.97 | -0.96 | -0.34 | -0.59 | -0.63 | -0.73 | -0.83 | -0.83 | -0.73 | -0.68 | -0.56 | -0.65 | -0.66 | -0.66 | -0.61 | -0.27 | -0.46 | -0.51 | -0.61 | -0.67 | -0.68 | -0.63 | -0.55 | -0.48 | -0.57 | -0.58 | -0.57 | -0.49 |
Peak Change From Baseline in IC Morning (NCT02347072)
Timeframe: Baseline and Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.454 |
| Spiriva Respimat | 0.374 |
| Placebo | 0.206 |
Peak Change From Baseline in IC Evening (NCT02347072)
Timeframe: Baseline and Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.421 |
| Spiriva Respimat | 0.297 |
| Placebo | 0.109 |
Normalized FEV1 AUC0-12 (NCT02347072)
Timeframe: Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.226 |
| Spiriva Respimat | 0.178 |
| Placebo | -0.026 |
Normalized FEV1 AUC12-24 (NCT02347072)
Timeframe: Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.159 |
| Spiriva Respimat | 0.039 |
| Placebo | -0.118 |
Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24 (NCT02347072)
Timeframe: Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.192 |
| Spiriva Respimat | 0.112 |
| Placebo | -0.072 |
Morning Pre-Dose Trough FEV1 on Day 29 (NCT02347072)
Timeframe: Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.140 |
| Spiriva Respimat | 0.097 |
| Placebo | -0.020 |
Morning Pre-Dose Trough FEV1 on Day 30 (NCT02347072)
Timeframe: Day 30
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.129 |
| Spiriva Respimat | 0.072 |
| Placebo | -0.073 |
Peak Change From Baseline in FEV1 Evening (NCT02347072)
Timeframe: Baseline and Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.395 |
| Spiriva Respimat | 0.230 |
| Placebo | 0.058 |
Peak Change From Baseline in FEV1 Morning (NCT02347072)
Timeframe: Baseline and Day 29
| Intervention | Liters (Least Squares Mean) |
|---|---|
| GFF MDI | 0.406 |
| Spiriva Respimat | 0.325 |
| Placebo | 0.129 |
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC)0-24 on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.166 |
| Placebo | -0.083 |
Peak Change from Baseline in IC following the morning dose on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.543 |
| Placebo | 0.208 |
FEV1 AUC0-12 on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.216 |
| Placebo | -0.039 |
FEV1 AUC12-24 on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.115 |
| Placebo | -0.127 |
Morning Pre-Dose Trough FEV on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.130 |
| Placebo | -0.012 |
Morning Pre-Dose Trough FEV1 on Day 30 (NCT02347085)
Timeframe: Day 30
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.090 |
| Placebo | -0.064 |
Peak Change From Baseline in FEV1 following evening Dose on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.344 |
| Placebo | 0.050 |
Peak Change From Baseline in FEV1 following the morning dose on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.410 |
| Placebo | 0.134 |
Peak Change from Baseline in Inspiratory Capacity (IC) following the evening dose on Day 29 (NCT02347085)
Timeframe: Day 29
| Intervention | Liters (Mean) |
|---|---|
| GFF MD (PT003) | 0.486 |
| Placebo | 0.105 |
Baseline values in FRC were defined as the corresponding values just before randomization on Day 1 of treatment (Week 0). Trough values were obtained prior to study drug administration. (NCT02424344)
Timeframe: Baseline and Week 4
| Intervention | Liters (Least Squares Mean) |
|---|---|
| AB/FF 400/12 μg | -0.162 |
| Placebo | -0.037 |
"The ET was the time from the increase in work rate to 75% Wmax to the point of symptom limitation.~Baseline measurements were taken prior to the IP dose on Day 1. Measurements at Week 8 were taken at 3 hours post-dose. Participants underwent a behavioural intervention (consisting of a telecoaching programme to enhance physical activity) between Week 4 and Week 8." (NCT02424344)
Timeframe: Baseline to Week 8
| Intervention | Seconds (Least Squares Mean) |
|---|---|
| AB/FF 400/12 μg | 50.7 |
| Placebo | -4.6 |
"Physical activity was assessed by means of measurement of activity parameters (e.g. number of steps) through a Dynaport MoveMonitor and completion of the Daily ProActive Physical Activity in chronic obstructive pulmonary disease (COPD) questionnaire.~Compliant criterion based on at least 8 hours per day, and at least 3 days per week. Participants underwent a behavioural intervention (consisting of a telecoaching programme to enhance physical activity) between Week 4 and Week 8.~Baseline was defined as mean of steps/day assessed during the week before the randomisation visit." (NCT02424344)
Timeframe: Week 8
| Intervention | Percent of inactive participants (Number) |
|---|---|
| AB/FF 400/12 μg | 41.53 |
| Placebo | 50.43 |
Participants were asked to read the appropriate package insert for their prescribed inhaler and then the investigator (or suitably qualified designee) demonstrated the proper use of the inhaler. The participant was then asked to self-administer their first dose of study treatment under the supervision of the investigator and any critical and non-critical errors were recorded. Individual instruments for assessing correct inhaler use were provided for each of the three devices used in this study. (NCT02446418)
Timeframe: Week 12 and Week 24
| Intervention | Percentage of participants (Number) | |
|---|---|---|
| Week 12; n= 195, 197 | Week 24; n= 191, 192 | |
| FF/VI | 94 | 97 |
| Usual ICS/LABA | 93 | 96 |
The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control during the past 4 weeks on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented. (NCT02446418)
Timeframe: Baseline and Week 12
| Intervention | Scores on a Scale (Least Squares Mean) |
|---|---|
| Usual ICS/LABA | 2.8 |
| FF/VI | 3.6 |
The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented. (NCT02446418)
Timeframe: Baseline and Week 24
| Intervention | Scores on a Scale (Least Squares Mean) |
|---|---|
| Usual ICS/LABA | 3.6 |
| FF/VI | 4.0 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Baseline-adjusted area under the serial FEV1-time curve was calculated from Time 0 to 12 hours on the first day of the Treatment Period (Day 1). FEV1 AUC0-12 was calculated from baseline-adjusted values using the linear trapezoidal method. The calculation assumed that at time of dosing (Time 0) the baseline adjusted FEV1 was also 0. The calculation proceeded over all available post-dose FEV1 assessments on Day 1 (including unscheduled time points, if any) using actual elapsed time from dosing. FEV1 baseline defined as the average of predose FEV1 values obtained on Day 1. If some of these values were missing, the average was calculated using the available values, however, a minimum of 2 predose FEV1 values were required; participants who had only 1 or no predose FEV1 measurements on Day 1 would have their FEV1 baseline missing, and the participant was to be excluded from analysis. (NCT02495168)
Timeframe: 0 to 12 hours on Day 1
| Intervention | Liter*hour (Lh) (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 3.637 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 3.584 |
| Placebo | 1.460 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42. If a participant had no predose assessment on Day 42, the average of all available predose assessments on the last day (for example, Early Termination visit [up to Day 50]) when at least 1 predose FEV1 assessments was available was imputed, if the participant discontinued due to lack of efficacy, otherwise there was no imputation. Baseline was defined as the average of at least 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1]. (NCT02495168)
Timeframe: Day 1 up to Day 50
| Intervention | liters (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 0.278 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 0.283 |
| Placebo | 0.094 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Baseline-adjusted area under the serial FEV1-time curve was calculated from Time 0 to 12 hours on the first day of the Treatment Period (Day 1). FEV1 AUC0-12 was calculated from baseline-adjusted values using the linear trapezoidal method. The calculation assumed that at time of dosing (Time 0) the baseline adjusted FEV1 was also 0. The calculation proceeded over all available post-dose FEV1 assessments on Day 1 (including unscheduled time points, if any) using actual elapsed time from dosing. FEV1 baseline defined as the average of predose FEV1 values obtained on Day 1. If some of these values were missing, the average was calculated using the available values, however, a minimum of 2 predose FEV1 values were required; participants who had only 1 or no predose FEV1 measurements on Day 1 would have their FEV1 baseline missing, and the participant was to be excluded from analysis. (NCT02495168)
Timeframe: 0 to 12 hours on Day 1
| Intervention | Lh (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 3.630 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 3.573 |
| Placebo | 1.449 |
FEV1 was measured using spirometry in accordance with the ATS/ERS consensus guidelines. Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42. If a participant had no predose assessment on Day 42, the average of all available predose assessments on the last day (for example, Early Termination visit [up to Day 50]) when at least 1 predose FEV1 assessments was available was imputed, if the participant discontinued due to lack of efficacy, otherwise there was no imputation. Baseline was defined as the average of at least 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1]. (NCT02495168)
Timeframe: Day 1 up to Day 50
| Intervention | liters (Mean) |
|---|---|
| Generic Budesonide/Formoterol Fumarate Dihydrate | 0.269 |
| Symbicort (Budesonide/Formoterol Fumarate Dihydrate) | 0.277 |
| Placebo | 0.124 |
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in tidal volume (Vt). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | mL (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 71.904 |
| Placebo | 14.281 |
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in mean inspiratory flow (tidal volume [Vt]/inspiratory time [Ti]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | mL/sec (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 26.533 |
| Placebo | 3.217 |
Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and IC (using an slow vital capacity [SVC] maneuver; IC/total lung capacity [TLC] will be used as a measure of resting hyperinflation). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | FEV1: L; ΔFVC: L; ΔIC: L (Least Squares Mean) | ||
|---|---|---|---|
| ΔFEV1 | ΔFVC | ΔIC | |
| Placebo | -0.004 | -0.052 | -0.024 |
| Symbicort pMDI | 0.187 | 0.259 | 0.256 |
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in minute ventilation (Ve). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | mL/min (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 838.232 |
| Placebo | -23.924 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | SaO2: % (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 0.422 |
| Placebo | 0.181 |
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in fractional inspiratory time (Ti/total cycle time [Ttot]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | ratio (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 0.012 |
| Placebo | -0.004 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | ΔHR: beats/min (Least Squares Mean) |
|---|---|
| Symbicort pMDI | -2.481 |
| Placebo | -2.831 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | ΔVCO2: mL/min (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 5.994 |
| Placebo | -4.251 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | mL/min (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 11.366 |
| Placebo | 1.252 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | mL/min/beats/min (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 0.256 |
| Placebo | 0.168 |
FEV1/FVC. For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | ratio (Least Squares Mean) |
|---|---|
| Symbicort pMDI | 0.017 |
| Placebo | -0.002 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). Modified Borg scale for dyspnea was self-administered at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21). The Borg scale is a 1-item instrument through which a subject reports dyspnea symptoms on a scale of 0-10 to quantify the intensity of dyspnea (where 10 is most intense). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Symbicort pMDI | -0.452 |
| Placebo | -0.248 |
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). (NCT02533505)
Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
| Intervention | breaths/min (Least Squares Mean) |
|---|---|
| Symbicort pMDI | -0.193 |
| Placebo | -0.430 |
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | cells/mm^2 (Mean) |
|---|---|
| Placebo | -14.80 |
| Dupilumab | 1.76 |
T-Lymphocytes i.e. CD3 positive cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | cells/mm^2 (Median) |
|---|---|
| Placebo | -36.70 |
| Dupilumab | 34.21 |
Serum functional dupilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method. (NCT02573233)
Timeframe: Week 0, Week 2, 6, 8, 12, 18, End of study (Week 24)
| Intervention | ng/mL (Mean) | ||||||
|---|---|---|---|---|---|---|---|
| Week 0 | Week 2 | Week 6 | Week 8 | Week 12 | Week 18 | Week 24 | |
| Dupilumab | 0.00 | 52675.00 | 59969.00 | 61097.95 | 67387.00 | 20728.17 | 1851.20 |
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during between the first administration of study medication to the end of the 12 week Post-treatment Period. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs. (NCT02573233)
Timeframe: Baseline up to Week 24
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Any TEAE | Any treatment emergent SAE | Any TEAE leading to death | Any TEAE leading to permanent discontinuation | |
| Dupilumab | 15 | 1 | 0 | 0 |
| Placebo | 17 | 0 | 0 | 0 |
"FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/s, and reported in ppb.~The average change in FeNO from baseline to Week 6 through Week 12 was calculated as follows: For each participant the change in FeNO from Baseline to Week 6, Week 8, Week 10 and Week 12 was calculated (value at Week X - value at baseline). Subsequently the weekly mean of these 4 change from baseline values was determined (Weeks 6, 8, 10 and 12). Using these weekly mean values the overall arithmetic mean and standard deviation of the average change in FeNO from baseline to Week 6 through Week 12 was calculated." (NCT02573233)
Timeframe: From Baseline to Week 6 through Week 12
| Intervention | ppb (Mean) |
|---|---|
| Placebo | 3.5 |
| Dupilumab | -16.0 |
Anti-drug antibodies were detected using a validated immunoassay. Incidence of ADA were classified as following: 1) Pre-existing immunoreactivity - an ADA positive response in the assay at baseline with all post treatment ADA results negative or an ADA positive response at baseline with all post treatment ADA responses less than 4-fold over baseline titer levels. 2) Treatment-emergent ADA: an ADA positive response in the assay post first dose, when baseline results were negative or missing. 3) Treatment-boosted ADA: an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. (NCT02573233)
Timeframe: From Baseline up to 24 weeks
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| With pre-existing immunoreactivity | With treatment-emergent ADA | With treatment-boosted ADA | |
| Dupilumab | 0 | 1 | 0 |
| Placebo | 1 | 0 | 0 |
T-helper i.e. CD4 positive lymphocytes were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | cells/mm^2 (Median) |
|---|---|
| Placebo | 7.26 |
| Dupilumab | 62.34 |
Mucin was identified by staining with Alcian-blue periodic acid-Schiff and/or immunostaining for MUC5AC and then the mucin-positive area was measured and expressed per square millimeter. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | cells/mm^2 (Mean) |
|---|---|
| Placebo | 64.09 |
| Dupilumab | -142.74 |
Inflammatory cells i.e. mast cells were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | cells/mm^2 (Mean) |
|---|---|
| Placebo | 2.37 |
| Dupilumab | -20.89 |
FeNO is a surrogate marker for airway inflammation. FeNO was analyzed using a NIOX instrument or similar analyzer using a flow rate of 50 mL/second, and reported in ppb. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | ppb (Mean) |
|---|---|
| Placebo | 3.9 |
| Dupilumab | -15.1 |
Inflammatory cells i.e. eosinophils were counted in the bronchial submucosa of biopsy thin sections using quantitative immunohistochemistry and reported as the number of cells per square millimeter. (NCT02573233)
Timeframe: Baseline, Week 12
| Intervention | cells/mm^2 (Median) |
|---|---|
| Placebo | 5.80 |
| Dupilumab | -6.04 |
Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 10.1 |
| Treatment B | 11.9 |
| Treatment C | 10.3 |
| Treatment D | 11.7 |
Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 3.21 |
| Treatment B | 3.14 |
| Treatment C | 3.23 |
| Treatment D | 3.01 |
Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A | 9.35 |
| Treatment B | 9.28 |
| Treatment C | 9.45 |
| Treatment D | 9.08 |
Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.080 |
| Treatment B | 0.250 |
| Treatment C | 0.040 |
| Treatment D | 0.250 |
Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | hours (Median) |
|---|---|
| Treatment A | 0.080 |
| Treatment B | 0.080 |
| Treatment C | 0.080 |
| Treatment D | 0.080 |
Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| Treatment A | 1080 |
| Treatment B | 686 |
| Treatment C | 1110 |
| Treatment D | 663 |
Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1820 |
| Treatment B | 1830 |
| Treatment C | 1670 |
| Treatment D | 1640 |
Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 55.4 |
| Treatment B | 63.0 |
| Treatment C | 46.8 |
| Treatment D | 53.7 |
Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 313 |
| Treatment B | 238 |
| Treatment C | 315 |
| Treatment D | 237 |
Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 3.37 |
| Treatment B | 3.88 |
| Treatment C | 3.36 |
| Treatment D | 3.76 |
Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 1710 |
| Treatment B | 1710 |
| Treatment C | 1570 |
| Treatment D | 1530 |
Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
| Intervention | pg*h/mL (Geometric Mean) |
|---|---|
| Treatment A | 46.1 |
| Treatment B | 52.6 |
| Treatment C | 39.0 |
| Treatment D | 42.8 |
FEV1 refers to the volume of air that an individual can exhale during a forced breath in 1 second. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | liters (Mean) |
|---|---|
| Treatment A | 0.188 |
| Treatment B | 0.170 |
| Treatment C | 0.173 |
| Treatment D | 0.153 |
PEFR is the highest rate at which gases can be expelled from the lungs via an open mouth. Its measurement is a simple procedure in which an individual takes a full inspiration and blows out as forcibly as possible into an instrument called a peak flow meter, which measures the maximal gas flow in an exhalation in liters per minute. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together. (NCT02631941)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | L/min (Mean) |
|---|---|
| Treatment A | 32.3 |
| Treatment B | 22.4 |
| Treatment C | 30.3 |
| Treatment D | 19.3 |
"FVC = Forced vital capacity. It is the full amount of air that can be exhaled with effort in a complete breath.~FEV1/FVC = Tiffenau-Pinelli Index. This parameter represents the measurement of the amount of air an individual can forcefully exhale from his/her lungs. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together." (NCT02631941)
Timeframe: At 75 min (1.25 hours) post-dose
| Intervention | Ratio (Mean) |
|---|---|
| Treatment A | 3.94 |
| Treatment B | 3.78 |
| Treatment C | 3.75 |
| Treatment D | 3.83 |
Morning pre-dose trough FEV1 (Forced Expiratory Volume in one second) at week 12 (NCT02727660)
Timeframe: at Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 ug | 0.072 |
| BFF MDI 160/9.6 ug | 0.069 |
| FF MDI 9.6 ug | 0.037 |
Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation over 52 weeks (NCT02727660)
Timeframe: over 52 weeks
| Intervention | Percentage of Subjects with Exacerbation (Number) | |||
|---|---|---|---|---|
| Percent of Subjects Exacerbated within 12 Weeks | Percent of Subjects Exacerbated within 24 Weeks | Percent of Subjects Exacerbated within 36 Weeks | Percent of Subjects Exacerbated within 52 Weeks | |
| BFF MDI 160/9.6 ug | 19.3 | 32.9 | 41.3 | 48.6 |
| BFF MDI 320/9.6 ug | 19.2 | 31.2 | 41.0 | 50.1 |
| FF MDI 9.6 ug | 24.8 | 35.1 | 46.2 | 54.8 |
The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI on health-related quality of life as compared to FF MDI in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. A decrease from baseline in SGRQ total score of 4 units or more is considered a clinically meaningful improvement in quality of life. (NCT02727660)
Timeframe: at Week 12
| Intervention | Percentage of Subjects (Number) |
|---|---|
| BFF MDI 320/9.6 ug | 52 |
| BFF MDI 160/9.6 ug | 54 |
| FF MDI 9.6 ug | 44 |
Change from baseline in average daily rescue Ventolin HFA use over 12 weeks (NCT02727660)
Timeframe: over 12 weeks
| Intervention | Puffs per day (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 ug | -0.9 |
| BFF MDI 160/9.6 ug | -0.9 |
| FF MDI 9.6 ug | -0.6 |
Change from baseline in morning pre-dose trough FEV1(Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI) (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.036 |
| BFF MDI 160/9.6 μg | 0.017 |
| FF MDI 9.6 μg | -0.003 |
| BD MDI 320 μg | -0.028 |
| Symbicort TBH 400/12 μg | 0.039 |
Change from baseline in morning pre-dose trough FEV1 (Forced expiratory volume in 1 second) at Week 24 (BFF MDI versus FF MDI) (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.036 |
| BFF MDI 160/9.6 μg | 0.017 |
| FF MDI 9.6 μg | -0.003 |
Changes from baseline in FEV1 AUC0-4 were normalized by taking the area under the curve value and dividing by the length of time under consideration (usually 4 hours). This normalization represents a weighted average of the change from baseline in FEV1 over the 4-hour period. (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.194 |
| BFF MDI 160/9.6 μg | 0.179 |
| FF MDI 9.6 ug | 0.161 |
| BD MDI 320 ug | 0.022 |
| Symbicort TBH 400/12 ug | 0.187 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 30 Minutes
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.207 |
| BFF MDI 160/9.6 μg | 0.207 |
| FF MDI 9.6 μg | 0.215 |
| BD MDI 320 μg | 0.047 |
| Symbicort TBH 400/12 μg | 0.190 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 4 Hours
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.230 |
| BFF MDI 160/9.6 μg | 0.215 |
| FF MDI 9.6 μg | 0.212 |
| BD MDI 320 μg | 0.073 |
| Symbicort TBH 400/12 μg | 0.209 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 5 Minutes
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.157 |
| BFF MDI 160/9.6 μg | 0.151 |
| FF MDI 9.6 μg | 0.160 |
| BD MDI 320 μg | 0.025 |
| Symbicort TBH 400/12 μg | 0.131 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 2 Hours
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.253 |
| BFF MDI 160/9.6 μg | 0.234 |
| FF MDI 9.6 μg | 0.244 |
| BD MDI 320 μg | 0.063 |
| Symbicort TBH 400/12 μg | 0.221 |
Peak change from baseline in FEV1 (Forced Expiratory Volume in 1 second) at Week 24 (BFF MDI vs BD MDI) (NCT02766608)
Timeframe: at Week 24
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.272 |
| BFF MDI 160/9.6 μg | 0.258 |
| FF MDI 9.6 μg | 0.243 |
| BD MDI 320 μg | 0.116 |
| Symbicort TBH 400/12 μg | 0.267 |
The SGRQ (St. George's Respiratory Questionnaire) is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of BFF MDI, FF MDI, BD MDI, & Symbicort TBH on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. (NCT02766608)
Timeframe: at Week 24
| Intervention | Percentage of Subjects (Number) |
|---|---|
| BFF MDI 320/9.6 μg | 48.12 |
| BFF MDI 160/9.6 μg | 47.22 |
| FF MDI 9.6 μg | 41.59 |
| BD MDI 320 μg | 43.62 |
| Symbicort TBH 400/12 μg | 53.78 |
Substudy: 12-hour PFT (Pulmonary Function Test) endpoint FEV1 (Forced Expiratory Volume) AUC0-12 (Area under the Curve 0-12). Changes from baseline in FEV1 AUC0-12 were normalized by taking the area under the curve value and dividing by the length of time under consideration. This normalization represents a weighted average of the change from baseline in FEV1 over the 12-hour period. (NCT02766608)
Timeframe: at Week 12
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.135 |
| BFF MDI 160/9.6 μg | 0.124 |
| FF MDI 9.6 μg | 0.117 |
| BD MDI 320 μg | 0.024 |
Time to first moderate or severe COPD (Chronic Obstructive Pulmonary Disease) exacerbation (BFF MDI vs FF MDI). (NCT02766608)
Timeframe: over 24 Weeks (timepoints of 4, 12 & 20 weeks)
| Intervention | Percentage of Participants (Number) | ||
|---|---|---|---|
| Percentage of Subjects to Exacerbate at 4 Weeks | Percentage of Subjects to Exacerbate at 12 Weeks | Percentage of Subjects to Exacerbate at 20 Weeks | |
| BD MDI 320 μg | 7.0 | 14.9 | 17.7 |
| BFF MDI 160/9.6 μg | 3.3 | 9.9 | 18.5 |
| BFF MDI 320/9.6 μg | 3.2 | 9.8 | 14.4 |
| FF MDI 9.6 μg | 5.5 | 15.0 | 20.5 |
| Symbicort TBH 400/12 ug | 1.8 | 8.6 | 13.1 |
Change from baseline in average daily rescue Ventolin HFA use over 24 weeks (BFF MDI vs BD MDI) (NCT02766608)
Timeframe: over 24 Weeks
| Intervention | Puffs per day (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | -1.3 |
| BFF MDI 160/9.6 μg | -1.3 |
| FF MDI 9.6 μg | -1.1 |
| BD MDI 320 μg | -0.6 |
| Symbicort TBH 400/12 μg | -1.2 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 15 Minutes
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.190 |
| BFF MDI 160/9.6 μg | 0.186 |
| FF MDI 9.6 μg | 0.201 |
| BD MDI 320 μg | 0.040 |
| Symbicort TBH 400/12 μg | 0.167 |
Time to onset of action Day 1 was evaluated by calculating change from baseline in FEV1 at each post-dose timepoint (5min, 15min, 30min, 1hr, 2hr, and 4hr), then comparing each treatment to BD MDI 320 ug. The first timepoint a statistically significant difference from BD MDI 320 ug of ≥100mL was determined to be time of onset for that treatment. (NCT02766608)
Timeframe: Day 1 - 1 Hour
| Intervention | Liter (Least Squares Mean) |
|---|---|
| BFF MDI 320/9.6 μg | 0.225 |
| BFF MDI 160/9.6 μg | 0.221 |
| FF MDI 9.6 μg | 0.236 |
| BD MDI 320 μg | 0.053 |
| Symbicort TBH 400/12 μg | 0.211 |
"To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) twice daily (BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate(20 μg).~Pre-dose spirometry was performed before the morning daily dose at Day 1 and Day 7 of each treatment period. Two sets of measurements were performed during the hour preceding the scheduled morning study drug administration, allowing approximately 30 minutes between them.~Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation." (NCT02796651)
Timeframe: Day 7: 30 min, 1 to 4 hours, 6 hours, 9 hours and 12 hours post-dose
| Intervention | Litre/Hour (Least Squares Mean) |
|---|---|
| Formoterol Fumarate 6 μg | 0.108 |
| Formoterol Fumarate (FF) 12 μg | 0.117 |
| Formoterol Fumarate (FF) 24 μg | 0.161 |
| Perforomist 20 μg | 0.122 |
| Placebo (Lactose Monohydrate) | 0.000 |
"To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg). Trough value was defined as the mean of the 2 pre-dose measurements on Day 7. If 1 of the 2 measurements was missing, the non-missing measurement was used as the trough value.~Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation." (NCT02796651)
Timeframe: At baseline and Day 7
| Intervention | Litre (Least Squares Mean) |
|---|---|
| Formoterol Fumarate 6 μg | 0.077 |
| Formoterol Fumarate (FF) 12 μg | 0.067 |
| Formoterol Fumarate (FF) 24 μg | 0.102 |
| Perforomist 20 μg | 0.061 |
| Placebo (Lactose Monohydrate) | 0.002 |
To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg). 6-hour serial spirometry was performed at Day 7 of each treatment period: spirometry was performed post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 6 hours post-dose Note: Perforomist® 40 μg treatment periods lasted for 1 day only. Hence, was not included in the calculation (NCT02796651)
Timeframe: Day 7: zero time to 6 hours post-dose
| Intervention | Litre/Hour (Least Squares Mean) |
|---|---|
| Formoterol Fumarate 6 μg | 0.166 |
| Formoterol Fumarate (FF) 12 μg | 0.177 |
| Formoterol Fumarate (FF) 24 μg | 0.225 |
| Perforomist 20 μg | 0.186 |
| Placebo (Lactose Monohydrate) | 0.007 |
To assess the bronchodilation of 3 doses of formoterol fumarate (6 μg, 12 μg and 24 μg) BID administered via Pressair® compared to placebo and to open-label nebulised formoterol fumarate (20 μg and 40 μg). 6-hour serial spirometry was performed at Day 1 of each treatment period: spirometry was performed post-dose at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours and 6 hours post-dose. (NCT02796651)
Timeframe: Day 1: zero time to 6 hours post-dose
| Intervention | Litre/Hour (Least Squares Mean) |
|---|---|
| Formoterol Fumarate 6 μg | 0.111 |
| Formoterol Fumarate (FF) 12 μg | 0.148 |
| Formoterol Fumarate (FF) 24 μg | 0.205 |
| Perforomist 20 μg | 0.195 |
| Perforomist 40 μg | 0.246 |
| Placebo (Lactose Monohydrate) | -0.019 |
To assess the non-inferior bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough)of AB 400 µg compared to TIO 18 μg after administration of oral inhalation powder BID via DPI to participants with COPD. (NCT02796677)
Timeframe: At baseline morning predose and Week 24
| Intervention | Litres (Least Squares Mean) |
|---|---|
| AB 400 μg | 0.064 |
| TIO 18 μg | 0.057 |
"To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 in morning pre-dose (trough) of AB/FF 400/12 µg compared to FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD.~Morning pre-dose (trough) FEV1 was defined as the average of the corresponding -30 minute and 0 minute before the morning study medication at Week 24. If one time-point was missing then the available one would be used as morning pre-dose." (NCT02796677)
Timeframe: At baseline morning predose and Week 24
| Intervention | Litres (Least Squares Mean) |
|---|---|
| AB/FF 400/12 μg | 0.080 |
| AB 400 μg | 0.066 |
| FF 12 μg | 0.025 |
| TIO 18 μg | 0.060 |
To assess the bronchodilatory effect by evaluating the mean changes from baseline in nAUC0-3/3h FEV1 of AB/FF 400/12 µg compared to AB 400 μg and and FF 12 μg after administration of oral inhalation powder BID via DPI to participants with COPD. (NCT02796677)
Timeframe: At Day 1 and Day 169
| Intervention | Litres (Least Squares Mean) |
|---|---|
| AB/FF 400/12 μg | 0.237 |
| AB 400 μg | 0.162 |
| FF 12 μg | 0.149 |
| TIO 18 μg | 0.151 |
"SGRQ was a A standardized self-completed tool used to measure impaired health and perceived well-being (quality of life) in respiratory diseases. The questionnaire contained 50 items divided into 3 (symptoms, activity and impacts) dimensions. Each of the three dimensions of the questionnaire is scored separately in the range from 0 to 100%, zero score indicating no impairment of life quality. A summary score utilizing responses to all items is the total SGRQ score which also ranges from 0 to 100%. The SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. Higher scores indicate poorer health. A decrease of at least 4 units in the SGRQ total score has been established as the criterion for minimal meaningful improvement. SGRQ responders will be those with a decrease in SGRQ total score of at least 4 units from baseline." (NCT02796677)
Timeframe: At baseline and Week 24
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| Number of responders -Yes | Number of responders- NO | |
| AB 400 μg | 188 | 195 |
| AB/FF 400/12 μg | 130 | 140 |
| FF 12 μg | 128 | 130 |
| TIO 18 μg | 197 | 192 |
"To assess the bronchodilatory effect by evaluating the mean changes from baseline in FEV1 at 1 hour post-dose of AB/FF 400/12 µg compared to AB 400 μg after administration of oral inhalation powder BID via DIP to participants with COPD.~Baseline was defined as the average of the two FEV1 values measured just prior to the administration of the first dose of investigational product (IP) at randomization Visit. If one of the two was missing, then the available one would be used as baseline value." (NCT02796677)
Timeframe: At baseline 1-hour postdose and Week 24
| Intervention | Litres (Least Squares Mean) |
|---|---|
| AB/FF 400/12 μg | 0.253 |
| AB 400 μg | 0.169 |
| FF 12 μg | 0.168 |
| TIO 18 μg | 0.161 |
FEV1 Area calculated over 12 hours (measurements at 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose) on Day 1 of treatment. Because this was a primary endpoint, Per Protocol Population used to calculate this endpoint. (NCT03015259)
Timeframe: Day 1
| Intervention | l * hr (Least Squares Mean) |
|---|---|
| Treatment 1 | 4.4453 |
| Treatment 2 | 4.2790 |
| Treatment 3 | 1.6876 |
Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42 (+/- 7 days). Baseline was defined as the average of 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: [FEV1 at end of treatment] - [Baseline FEV1]. (NCT03015259)
Timeframe: Day 1 - Day 49
| Intervention | liter (Least Squares Mean) |
|---|---|
| Treatment 1 | 0.3096 |
| Treatment 2 | 0.3077 |
| Treatment 3 | 0.1236 |
Number of participants reporting at least one adverse event (safety population) (NCT03015259)
Timeframe: 6 Weeks
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Upper respiratory tract infection | Nasopharyngitis | Viral upper respiratory tract infection | Bronchitis | Asthma | Cough | Headache | Chest discomfort | |
| Treatment 1 | 12 | 7 | 6 | 3 | 17 | 4 | 4 | 1 |
| Treatment 2 | 15 | 11 | 4 | 4 | 24 | 4 | 8 | 0 |
| Treatment 3 | 7 | 4 | 1 | 2 | 39 | 3 | 2 | 2 |
Maximum plasma concentration (Cmax) of Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 4.884 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 5.286 |
| PT003 (GFF MDI) 14.4/9.6 µg | 5.674 |
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 8 (NCT03075267)
Timeframe: Day 8
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 69.487 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 77.078 |
| PT003 (GFF MDI) 14.4/9.6 µg | 72.636 |
Maximum plasma concentration (Cmax) of Glycopyrronium Day 8 (NCT03075267)
Timeframe: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 11.303 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 11.754 |
| PT003 (GFF MDI) 14.4/9.6 µg | 13.124 |
Accumulation ratio for Cmax (RAC [Cmax]) - Budesonide (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | Ratio (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1.400 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 1.406 |
Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium (NCT03075267)
Timeframe: Day 1 and Day 8
| Intervention | Ratio (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 3.324 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 3.030 |
| PT003 (GFF MDI) 14.4/9.6 µg | 3.189 |
Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol (NCT03075267)
Timeframe: Day 1 and Day 8
| Intervention | Ratio (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1.718 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 1.835 |
| PT003 (GFF MDI) 14.4/9.6 µg | 1.620 |
Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide (NCT03075267)
Timeframe: Day 1 and Day 8
| Intervention | Ratio (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1.455 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 1.539 |
Elimination half-life (t½) - Budesonide Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 4.572 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 3.168 |
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 35.465 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 33.014 |
| PT003 (GFF MDI) 14.4/9.6 µg | 43.537 |
Accumulation ratio for Cmax (RAC [Cmax]) - Formoterol (NCT03075267)
Timeframe: Day 1 and Day 8
| Intervention | Ratio (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1.678 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 1.706 |
| PT003 (GFF MDI) 14.4/9.6 µg | 1.668 |
Apparent total body clearance (CL/F) - Budesonide Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | L/h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 165.271 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 182.508 |
Apparent total body clearance (CL/F) - Formoterol Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | L/h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 155.801 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 131.286 |
| PT003 (GFF MDI) 14.4/9.6 µg | 135.962 |
Time to maximum plasma concentration (tmax) - Glycopyrronium Day 8 (NCT03075267)
Timeframe: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Median) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.333 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.333 |
| PT003 (GFF MDI) 14.4/9.6 µg | 0.333 |
Time to maximum plasma concentration (tmax) - Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Median) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.100 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.100 |
| PT003 (GFF MDI) 14.4/9.6 µg | 0.100 |
Time to maximum plasma concentration (tmax) - Formoterol Day 8 (NCT03075267)
Timeframe: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Median) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.100 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.100 |
| PT003 (GFF MDI) 14.4/9.6 µg | 0.100 |
Time to maximum plasma concentration (tmax) - Formoterol Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Median) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.833 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.100 |
| PT003 (GFF MDI) 14.4/9.6 µg | 0.100 |
Time to maximum plasma concentration (tmax) - Budesonide Day 8 (NCT03075267)
Timeframe: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Median) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.333 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.333 |
Time to maximum plasma concentration (tmax) - Budesonide Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Median) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.333 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.333 |
Accumulation ratio for Cmax (RAC [Cmax]) - Glycopyrronium (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | Ratio (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 2.383 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 2.319 |
| PT003 (GFF MDI) 14.4/9.6 µg | 2.412 |
Terminal elimination rate constant (λz) - Formoterol - Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | 1/h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.136 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.123 |
| PT003 (GFF MDI) 14.4/9.6 µg | 0.123 |
Terminal elimination rate constant (λz) - Budesonide - Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | 1/h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.152 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.219 |
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 29.400 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 27.197 |
| PT003 (GFF MDI) 14.4/9.6 µg | 29.002 |
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 8 (NCT03075267)
Timeframe: Day 8
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 81.936 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 85.322 |
| PT003 (GFF MDI) 14.4/9.6 µg | 83.499 |
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 47.843 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 46.492 |
| PT003 (GFF MDI) 14.4/9.6 µg | 53.583 |
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 8 (NCT03075267)
Timeframe: Day 8
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 2509.888 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 1249.615 |
Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1747.910 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 811.812 |
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 17.616 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 17.707 |
| PT003 (GFF MDI) 14.4/9.6 µg | 20.287 |
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Formoterol Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 48.326 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 47.408 |
| PT003 (GFF MDI) 14.4/9.6 µg | 45.950 |
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Budesonide Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1884.912 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 830.012 |
Terminal elimination rate constant (λz) - Glycopyrronium - Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | 1/h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 0.122 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 0.081 |
| PT003 (GFF MDI) 14.4/9.6 µg | 0.112 |
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Formoterol Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 61.617 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 73.123 |
| PT003 (GFF MDI) 14.4/9.6 µg | 70.608 |
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Budesonide Day 1 (NCT03075267)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1936.211 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 876.673 |
Apparent volume of distribution (Vd/F) - Glycopyrronium - Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | L (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 2172.038 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 2123.999 |
| PT003 (GFF MDI) 14.4/9.6 µg | 1864.314 |
Apparent volume of distribution (Vd/F) - Formoterol - Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | L (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1125.215 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 1000.172 |
| PT003 (GFF MDI) 14.4/9.6 µg | 1035.257 |
Apparent volume of distribution (Vd/F) - Budesonide - Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | L (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 1090.237 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 834.269 |
Apparent total body clearance (CL/F) - Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | L/h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 406.038 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 436.184 |
| PT003 (GFF MDI) 14.4/9.6 µg | 330.757 |
Elimination half-life (t½) - Formoterol Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 5.098 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 5.657 |
| PT003 (GFF MDI) 14.4/9.6 µg | 5.628 |
Elimination half-life (t½) - Glycopyrronium Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | h (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 5.676 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 8.539 |
| PT003 (GFF MDI) 14.4/9.6 µg | 6.194 |
Maximum plasma concentration (Cmax) of Budesonide Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 459.308 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 224.298 |
Maximum plasma concentration (Cmax) of Budesonide Day 8 (NCT03075267)
Timeframe: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 626.435 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 315.425 |
Maximum plasma concentration (Cmax) of Formoterol Day 1 (NCT03075267)
Timeframe: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 9.651 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 9.932 |
| PT003 (GFF MDI) 14.4/9.6 µg | 10.618 |
Maximum plasma concentration (Cmax) of Formoterol Day 8 (NCT03075267)
Timeframe: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 (BGF MDI) 320/14.4/9.6 µg | 16.125 |
| PT010 (BGF MDI) 160/14.4/9.6 µg | 16.945 |
| PT003 (GFF MDI) 14.4/9.6 µg | 17.710 |
"Heart rate (HR) AUC(0-4h) and HR peak(0-4h), normalized by time (in bpm).~Results are shown as change from pre-dose on Day 14 (in bpm).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~Definitions:~HR=Heart rate; HR AUC(0-4h)=Area under the curve between 0 and 4 h for heart rate; HR peak(0-4h)=The maximum observed value over 4 h after dosing;" (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | bpm (Mean) | |
|---|---|---|
| HR AUC(0-4h) | HR peak(0-4h) | |
| Treatment A | -0.4 | 3.5 |
| Treatment B | 0.5 | 5.1 |
| Treatment C | 0.4 | 5.1 |
| Treatment D | 1.3 | 5.3 |
| Treatment E | -0.2 | 4.3 |
| Treatment F | 0.9 | 4.8 |
"Spirometry used to measure FEV1, was performed according to internationally accepted standards. Results show the change from baseline in FEV1 AUC(0-12h), normalized by time on Day 14; it was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Definitions:~AUC=Area under the curve; AUC(0-12h)=AUC between 0 and 12 h; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period; FEV1=Forced expiratory volume in the 1st second;" (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.174 |
| Treatment B | 0.221 |
| Treatment C | 0.197 |
| Treatment D | 0.231 |
| Treatment E | 0.064 |
| Treatment F | 0.208 |
"Spirometry used to measure FEV1, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.181 |
| Treatment B | 0.221 |
| Treatment C | 0.260 |
| Treatment D | 0.282 |
| Treatment E | 0.067 |
| Treatment F | 0.239 |
"Patients achieving onset of action, defined as a change from baseline in post-dose FEV1 ≥12% and ≥200 mL, on Day 1. These are the subjects who contributed to the results, reported as median and 95% CI for 'Time to onset of action' presented in the Outcome Measure 13, above.~For patients receiving the same treatment twice, the analysis includes only data from the first instance of each treatment.~Definitions:~Onset of action=Change from baseline in post-dose FEV1 ≥12% and ≥200 mL; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose);" (NCT03086460)
Timeframe: Baseline, Day 1 post-dose
| Intervention | Participants (Count of Participants) |
|---|---|
| Treatment A | 23 |
| Treatment B | 22 |
| Treatment C | 30 |
| Treatment D | 29 |
| Treatment E | 11 |
| Treatment F | 31 |
"Spirometry, used to measure FEV1, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.071 |
| Treatment B | 0.102 |
| Treatment C | 0.073 |
| Treatment D | 0.149 |
| Treatment E | 0.037 |
| Treatment F | 0.126 |
"Spirometry, used to measure FVC, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.048 |
| Treatment B | 0.044 |
| Treatment C | 0.048 |
| Treatment D | 0.114 |
| Treatment E | 0.053 |
| Treatment F | 0.114 |
"The primary analysis was repeated, considering patients as randomized and including only the first instance of each treatment.~Patients receiving the same treatment in more than one period were included in the analysis with only data from the first instance of each treatment." (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.169 |
| Treatment B | 0.224 |
| Treatment C | 0.196 |
| Treatment D | 0.232 |
| Treatment E | 0.058 |
| Treatment F | 0.206 |
"The primary analysis was repeated, considering only patients and treatment periods for which treatment was assigned on or after the randomization error occurred.~The number of patients shown represents those with at least one post-baseline assessment available." (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.129 |
| Treatment B | 0.180 |
| Treatment C | 0.159 |
| Treatment D | 0.179 |
| Treatment E | -0.006 |
| Treatment F | 0.170 |
"Vital signs -- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were measured at pre-specified times (at baseline - pre dose and on Day 14 of each treatment period or on the day of early study termination).~Results are shown by treatment group, as change from baseline (in mmHg).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~Definitions:~For safety variables, the baseline for each treatment period was defined as pre-dose measurements on Day 1 of each treatment period; Day 14=The day of the last dosing of a treatment period. Day 14 of the second, third, and fourth treatment periods (day of last dosing); treatments were separated by a 2-week wash-out interval;" (NCT03086460)
Timeframe: Baseline, Day 1 and Day 14 post-dose
| Intervention | mmHg (Mean) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SBP, Day 1, 30 min post-dose | SBP, Day 1, 1 h post-dose | SBP, Day 1, 4 h post-dose | SBP, Day 1, 8 h post-dose | SBP, Day 1, 12 h post-dose | SBP, Day 14, pre-dose | SBP, Day 14, 30 min post-dose | SBP, Day 14, 1 h post-dose | SBP, Day 14, 4 h post-dose | SBP, Day 14, 8 h post-dose | SBP, Day 14, 12 h post-dose | DBP, Day 1, 30 min post-dose | DBP, Day 1, 1 h post-dose | DBP, Day 1, 4 h post-dose | DBP, Day 1, 8 h post-dose | DBP, Day 1, 12 h post-dose | DBP, Day 14, pre-dose | DBP, Day 14, 30 min post-dose | DBP, Day 14, 1 h post-dose | DBP, Day 14, 4 h post-dose | DBP, Day 14, 8 h post-dose | DBP, Day 14, 12 h post-dose | |
| Treatment A | -1.2 | -0.1 | 1.7 | 0.8 | 1.8 | 1.0 | 0.3 | 0.1 | 0.9 | 0.7 | 1.2 | -2.1 | 0.0 | -0.6 | -1.5 | -0.5 | -1.2 | -0.2 | -0.3 | -1.0 | -1.1 | 0.0 |
| Treatment B | 0.2 | 0.5 | 0.4 | 0.2 | 2.1 | -1.8 | -3.1 | -1.8 | 0.1 | 1.3 | 1.0 | -1.5 | -1.9 | -1.4 | -0.9 | -0.1 | 0.1 | -2.1 | -2.4 | -1.5 | -1.0 | -0.7 |
| Treatment C | -0.8 | -0.6 | -0.9 | 1.1 | 3.0 | 0.0 | -0.7 | -1.8 | -1.4 | 1.1 | 1.5 | -1.2 | -0.4 | -0.4 | -0.4 | 0.4 | 1.1 | -0.8 | -0.5 | -1.7 | 0.3 | 0.7 |
| Treatment D | -1.2 | -0.6 | 0.9 | 0.7 | 1.4 | -0.4 | -0.7 | -1.9 | 1.0 | 0.6 | 4.4 | -2.0 | -1.6 | -1.0 | -1.9 | -1.0 | -0.1 | -2.9 | -2.4 | -2.5 | -2.6 | -0.6 |
| Treatment E | -0.5 | -0.8 | 0.2 | 0.5 | -0.1 | -2.5 | -3.6 | -1.7 | -0.5 | -3.3 | -0.3 | -0.3 | -2.5 | -1.6 | -1.7 | -0.3 | -0.6 | -1.5 | -1.8 | 0.4 | -1.7 | 1.4 |
| Treatment F | -0.8 | -0.8 | 0.5 | 2.5 | 3.4 | -0.3 | -2.5 | -1.1 | -0.8 | 0.6 | 2.5 | -1.2 | -1.7 | -1.0 | 0.4 | 0.0 | -0.7 | -2.0 | -1.6 | -2.3 | -1.3 | -0.1 |
"Spirometry, used to measure FVC, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 0.158 | 0.135 |
| Treatment B | 0.186 | 0.146 |
| Treatment C | 0.159 | 0.136 |
| Treatment D | 0.215 | 0.194 |
| Treatment E | 0.036 | 0.050 |
| Treatment F | 0.213 | 0.177 |
"Spirometry, used to measure FVC, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 0.111 | 0.103 |
| Treatment B | 0.156 | 0.134 |
| Treatment C | 0.160 | 0.120 |
| Treatment D | 0.182 | 0.142 |
| Treatment E | 0.059 | 0.060 |
| Treatment F | 0.172 | 0.134 |
"12-lead electrocardiogram (ECG) parameters were monitored during the study. Results are shown by treatment group, as change from baseline (in msec).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | msec (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1, 30 min post-dose | Day 1, 1h post-dose | Day 1, 4h post-dose | Day 1, 8h post-dose | Day 1, 12h post-dose | Day 14, pre-dose | Day 14, 30 min post-dose | Day 14, 1h post-dose | Day 14, 4h post-dose | Day 14, 8h post-dose | Day 14, 12h post-dose | |
| Treatment A | -0.1 | 1.1 | -1.2 | -1.9 | -3.4 | 1.3 | -0.2 | 1.0 | -1.5 | -2.6 | -5.0 |
| Treatment B | 1.6 | 2.2 | 1.6 | -0.5 | -2.3 | 3.7 | 4.5 | 5.7 | 2.5 | 1.5 | 1.7 |
| Treatment C | -1.3 | -1.1 | -1.5 | -3.0 | -3.8 | -1.7 | -1.5 | 0.1 | -2.5 | -3.2 | -4.8 |
| Treatment D | -3.6 | -0.7 | -4.0 | -2.6 | -3.0 | -2.9 | -3.1 | -1.6 | -3.2 | -5.4 | -1.4 |
| Treatment E | 1.0 | 0.4 | -1.6 | -2.4 | -2.6 | 0.1 | 3.4 | 5.2 | 0.8 | -1.1 | 0.1 |
| Treatment F | 3.2 | 2.0 | 1.9 | -0.0 | -1.7 | 2.2 | 5.1 | 6.1 | 1.3 | 0.8 | -0.3 |
"Serum potassium level was monitored during the study. Results are shown by treatment group, as change from baseline (in mmol/L).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | mmol/L (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1; 1.5h post-dose | Day 1; 3h post-dose | Day 1; 5h post-dose | Day 1; 7h post-dose | Day 1; 11h post-dose | Day 14; pre-dose | Day 14; 1.5h post-dose | Day 14; 3h post-dose | Day 14; 5h post-dose | Day 14; 7h post-dose | Day 14; 11h post-dose | |
| Treatment A | -0.01 | -0.06 | -0.14 | -0.02 | 0.07 | 0.06 | -0.02 | -0.04 | -0.02 | 0.05 | 0.11 |
| Treatment B | -0.05 | -0.08 | -0.03 | -0.00 | 0.02 | -0.02 | -0.03 | -0.09 | -0.05 | 0.06 | 0.05 |
| Treatment C | -0.08 | -0.23 | -0.12 | -0.05 | -0.08 | 0.08 | -0.10 | -0.13 | -0.01 | 0.09 | 0.03 |
| Treatment D | -0.17 | -0.28 | -0.19 | -0.16 | -0.10 | -0.14 | -0.23 | -0.24 | -0.26 | -0.19 | -0.06 |
| Treatment E | -0.06 | 0.03 | -0.04 | 0.04 | 0.01 | 0.05 | -0.03 | -0.00 | 0.00 | 0.02 | 0.01 |
| Treatment F | -0.18 | -0.21 | -0.20 | -0.14 | -0.13 | -0.13 | -0.15 | -0.15 | -0.15 | -0.09 | -0.02 |
"Heart rate HR AUC(0-4h) normalized by time. Results are shown by treatment group, as change from baseline (in bpm).~The HR AUC(0-4h) normalized by time is calculated based on the actual times, using the linear trapezoidal rule.~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | bpm (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 0.2 | 2.3 |
| Treatment B | 0.8 | 0.2 |
| Treatment C | 2.7 | 3.5 |
| Treatment D | 3.0 | 3.3 |
| Treatment E | -1.0 | -0.1 |
| Treatment F | 0.3 | 1.2 |
"Spirometry, used to measure FVC, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 0.331 | 0.310 |
| Treatment B | 0.347 | 0.331 |
| Treatment C | 0.354 | 0.304 |
| Treatment D | 0.367 | 0.350 |
| Treatment E | 0.216 | 0.198 |
| Treatment F | 0.385 | 0.340 |
"Serum glucose level was monitored during the study. Results are shown by treatment group, as change from baseline (in mmol/L).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | mmol/L (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1; 1.5h post-dose | Day 1; 3h post-dose | Day 1; 5h post-dose | Day 1; 7h post-dose | Day 1; 11h post-dose | Day 14; pre-dose | Day 14; 1.5h post-dose | Day 14; 3h post-dose | Day 14; 5h post-dose | Day 14; 7h post-dose | Day 14; 11h post-dose | |
| Treatment A | 0.49 | 0.45 | 0.83 | 0.81 | 0.98 | -0.34 | 0.09 | 0.09 | 0.04 | -0.04 | 0.39 |
| Treatment B | 0.34 | 0.54 | 1.12 | 0.42 | 1.08 | 0.00 | 0.26 | 0.77 | 0.90 | 0.60 | 1.30 |
| Treatment C | 0.57 | 1.10 | 1.11 | 1.24 | 1.89 | 0.49 | 0.97 | 1.31 | 1.12 | 0.73 | 1.50 |
| Treatment D | 1.19 | 1.79 | 1.58 | 1.37 | 1.42 | 0.49 | 1.21 | 1.51 | 1.16 | 1.09 | 1.47 |
| Treatment E | 0.47 | 0.26 | 0.51 | 0.84 | 1.40 | 0.37 | 0.35 | 0.25 | 0.32 | 0.25 | 1.03 |
| Treatment F | -0.06 | 0.39 | 0.44 | 0.61 | 0.90 | -0.03 | -0.03 | 0.16 | 0.53 | 0.18 | 0.68 |
"Spirometry, used to measure FEV1, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 0.359 | 0.346 |
| Treatment B | 0.370 | 0.373 |
| Treatment C | 0.393 | 0.349 |
| Treatment D | 0.430 | 0.389 |
| Treatment E | 0.178 | 0.183 |
| Treatment F | 0.416 | 0.367 |
"Spirometry used to measure FEV1, was performed according to internationally accepted standards.~Patients receiving the same treatment during two periods are considered twice in the ANCOVA model (once for each period attended).~Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 0.220 | 0.214 |
| Treatment B | 0.250 | 0.251 |
| Treatment C | 0.270 | 0.231 |
| Treatment D | 0.317 | 0.278 |
| Treatment E | 0.047 | 0.061 |
| Treatment F | 0.288 | 0.259 |
"12-lead electrocardiogram (ECG) parameters were monitored during the study. Results are shown by treatment group, as change from baseline (in msec).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | msec (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1, 30 min post-dose | Day 1, 1h post-dose | Day 1, 4h post-dose | Day 1, 8h post-dose | Day 1, 12h post-dose | Day 14, pre-dose | Day 14, 30 min post-dose | Day 14, 1h post-dose | Day 14, 4h post-dose | Day 14, 8h post-dose | Day 14, 12h post-dose | |
| Treatment A | 3.9 | 2.1 | 2.5 | 2.4 | 2.0 | 1.5 | 4.4 | 4.0 | 3.8 | 3.4 | 3.7 |
| Treatment B | 3.8 | 1.4 | 1.5 | 1.1 | 0.9 | -0.4 | 1.0 | 1.0 | 0.9 | 1.7 | 1.7 |
| Treatment C | 2.7 | 3.9 | 0.8 | 0.6 | -0.3 | 1.6 | 3.5 | 1.9 | 1.1 | 1.7 | -0.9 |
| Treatment D | 4.9 | 4.2 | 2.4 | 0.8 | 1.1 | 5.8 | 10.4 | 7.7 | 5.0 | 2.2 | 3.7 |
| Treatment E | -0.2 | 0.4 | -2.4 | -0.2 | -1.5 | -2.3 | 1.9 | 0.9 | -1.1 | 1.5 | -0.6 |
| Treatment F | 1.4 | -0.9 | -1.3 | -2.4 | -2.2 | 1.2 | 1.7 | 0.6 | -1.1 | 0.4 | -1.6 |
"12-lead electrocardiogram (ECG) parameters were monitored during the study. Results are shown by treatment group, as change from baseline (in msec).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | msec (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1, 30 min post-dose | Day 1, 1h post-dose | Day 1, 4h post-dose | Day 1, 8h post-dose | Day 1, 12h post-dose | Day 14, pre-dose | Day 14, 30 min post-dose | Day 14, 1h post-dose | Day 14, 4h post-dose | Day 14, 8h post-dose | Day 14, 12h post-dose | |
| Treatment A | 1.2 | 1.3 | 1.2 | 0.6 | 0.5 | 0.5 | 1.4 | 1.3 | 2.0 | 0.7 | 0.8 |
| Treatment B | 1.2 | 1.0 | 2.1 | 0.9 | 1.0 | 1.0 | 1.6 | 0.9 | 1.8 | 1.2 | 0.4 |
| Treatment C | 1.7 | 1.2 | 2.2 | 1.3 | 1.0 | -0.5 | 0.5 | 0.4 | 0.6 | 0.1 | 0.3 |
| Treatment D | 1.1 | 1.6 | 2.1 | 0.5 | 0.9 | 1.7 | 2.4 | 2.3 | 2.8 | 1.4 | 1.4 |
| Treatment E | 0.8 | 1.0 | 1.0 | -0.2 | 0.4 | -0.9 | -0.3 | 0.0 | -0.2 | -0.8 | -1.0 |
| Treatment F | 1.3 | 1.4 | 1.1 | 0.5 | 0.8 | 0.8 | 1.7 | 1.0 | 1.1 | 0.9 | 0.5 |
"Results are shown by treatment group, as change from baseline (in bpm).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period." (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | bpm (Mean) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1, 30 min post-dose | Day 1, 1h post-dose | Day 1, 4h post-dose | Day 1, 8h post-dose | Day 1, 12h post-dose | Day 14, pre-dose | Day 14, 30 min post-dose | Day 14, 1h post-dose | Day 14, 4h post-dose | Day 14, 8h post-dose | Day 14, 12h post-dose | |
| Treatment A | 0.3 | -1.3 | 2.1 | 5.0 | 5.1 | 2.5 | 2.9 | 1.9 | 2.8 | 5.5 | 7.4 |
| Treatment B | 1.2 | 0.3 | 1.5 | 2.4 | 5.5 | 0.1 | -0.8 | -1.2 | 2.3 | 3.5 | 7.5 |
| Treatment C | 1.7 | 2.7 | 3.3 | 5.0 | 5.5 | 3.1 | 1.6 | 1.6 | 6.7 | 4.9 | 6.7 |
| Treatment D | 2.5 | 1.5 | 5.3 | 3.9 | 7.6 | 2.0 | 4.3 | 3.2 | 3.4 | 3.8 | 5.4 |
| Treatment E | -2.4 | -1.8 | 0.2 | 0.5 | 2.4 | 0.7 | -1.5 | -1.2 | 1.8 | 1.6 | 0.5 |
| Treatment F | -0.3 | -1.2 | 3.2 | 2.1 | 5.2 | 0.4 | 1.3 | 0.4 | 2.3 | 2.6 | 5.1 |
"Spirometry, used to measure FEV1, was performed according to internationally accepted standards.~For patients receiving the same treatment twice, the analysis includes only data from the first instance of each treatment.~Definitions:~Time to onset of action=The time (in minutes) from receiving the study drug on Day 1, until the FEV1 change from baseline is ≥200 mL; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose) on Day 1 of the treatment period;" (NCT03086460)
Timeframe: Baseline, Day 1 post-dose
| Intervention | minutes (Median) |
|---|---|
| Treatment A | 358.8 |
| Treatment B | 60.3 |
| Treatment C | 33.6 |
| Treatment D | 44.3 |
| Treatment E | NA |
| Treatment F | 45.5 |
"Patients receiving the same treatment during two treatment periods are considered twice in the ANCOVA model (once for each period attended).~Patients considered in this analysis are those with at least one available post-baseline assessment." (NCT03086460)
Timeframe: Baseline, Day 14 post-dose
| Intervention | Litres (Least Squares Mean) |
|---|---|
| Treatment A | 0.144 |
| Treatment B | 0.194 |
| Treatment C | 0.170 |
| Treatment D | 0.198 |
| Treatment E | 0.037 |
| Treatment F | 0.184 |
"Heart rate (HR) peak(0-4h) normalized by time.~Results are shown by treatment group, as change from baseline (in bpm).~For patients receiving the same treatment in 2 periods, the average of the 2 available data points was considered in the calculation.~For safety variables, the baseline for each period was defined as pre-dose measurements on Day 1 of each treatment period.~Definitions:~HR=Heart rate; HR peak(0-4h)=The maximum observed value over 4 hours following dosing;" (NCT03086460)
Timeframe: Baseline, Day 1, Day 14 post-dose
| Intervention | bpm (Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Treatment A | 4.7 | 6.1 |
| Treatment B | 4.4 | 4.8 |
| Treatment C | 6.5 | 8.3 |
| Treatment D | 7.5 | 7.3 |
| Treatment E | 2.9 | 4.4 |
| Treatment F | 5.1 | 5.2 |
Change from baseline in the 6-item EMSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The EMSCI collected data about the frequency and severity of early morning symptoms and the impact of COPD symptoms on early morning activity in participants with COPD. Participants completed a daily electronic patient-reported outcome (ePRO) questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). TI = Time interval. (NCT03162055)
Timeframe: From Baseline (Day -7) up to 24 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | -0.142 |
| Umeclidinium/Vilanterol | -0.176 |
The baseline dyspnea index (BDI) and TDI consist of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. For the BDI, each of these 3 components were rated in 5 grades from 0 (very severe) to 4 (no impairment), and were summed to form a baseline total score from 0 to 12. For the TDI, changes in dyspnea were rated for each component by 7 grades from -3 (major deterioration) to +3 (major improvement), and were added to form a TDI focal score from -9 to +9. Baseline is defined as the latest BDI assessment within 7 days before or at randomization (Day 1). (NCT03162055)
Timeframe: From Baseline (Day -7 or 1) up to 24 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | 1.23 |
| Umeclidinium/Vilanterol | 1.60 |
The CAT is used to quantify the impact of COPD symptoms on health status. The CAT has a scoring range of 0-40, and it is calculated as the sum of the responses given for each of the 8 items (scored on a 6-point scale from 0 to 5), with higher scores indicating a higher impact of COPD symptoms on health status. If the response to 1 of the 8 items is missing, the missing item was considered equal to the average of the 7 non-missing items for that participant. If more than 1 item is missing the score was considered missing. Baseline is defined as the latest assessment within 7 days before or at randomization (Day 1). (NCT03162055)
Timeframe: From Baseline (Day -7 or 1) up to 24 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | -2.97 |
| Umeclidinium/Vilanterol | -3.56 |
The percentage of participants with an increase in FEV1 of >=100 mL from baseline at 5 minutes post-dosing on Day 1 was determined to assess the early onset of action. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1). Only data assigned to the 5 minute window was used to determine response. Participants with missing data were considered non-responders for the analysis. (NCT03162055)
Timeframe: 5 minutes post-dose on Day 1
| Intervention | Percentage of participants (Number) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | 60.1 |
| Umeclidinium/Vilanterol | 40.8 |
Peak change from baseline in IC is defined as the maximum of the IC assessments within the 2 hours post-dosing time windows at each visit minus baseline. Baseline is defined as the average of available evaluable -60 and -30 minute pre-dose assessments conducted at randomization (Day 1). (NCT03162055)
Timeframe: From Baseline (Day 1) up to 24 weeks
| Intervention | mL (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | 363.1 |
| Umeclidinium/Vilanterol | 378.3 |
To assess the effects of GFF relative to UV on lung function in PP analysis set population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). (NCT03162055)
Timeframe: From Baseline (Day 1) up to 24 weeks
| Intervention | mL (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | 293.5 |
| Umeclidinium/Vilanterol | 296.9 |
To assess the effects of GFF relative to UV on lung function in FAS population as measured by peak change from baseline in FEV1 is defined as the maximum of the FEV1 assessments within the 2 hours post-dosing time windows at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). (NCT03162055)
Timeframe: From Baseline (Day 1) up to 24 weeks
| Intervention | mL (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | 299.1 |
| Umeclidinium/Vilanterol | 300.8 |
Change from baseline in the 6-item NiSCI Symptom Severity Score was derived by averaging the responses from a participant on the 6 item-level symptom scores (scored on a 4-point scale from 1 to 4, whereas 1= mild and 4= very severe). The NiSCI collected data about the frequency and severity of night-time symptoms and the impact of COPD symptoms on night-time awakenings in participants with COPD. Participants completed a daily ePRO questionnaire for their COPD symptoms. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). (NCT03162055)
Timeframe: From Baseline (Day -7) up to 24 weeks
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | -0.165 |
| Umeclidinium/Vilanterol | -0.207 |
To assess the effects of GFF relative to UV on lung function as measured by change from baseline in morning pre-dose trough FEV1 is defined as the average of the -60 and -30 minute pre-dose values at each visit minus baseline using spirometry. Baseline is defined as the mean of the non-missing -60 and -30 minute values obtained prior to dosing at randomization (Day 1). BR a/s = bronchodilator responsiveness to albuterol/salbutamol. (NCT03162055)
Timeframe: From Baseline (Day 1) up to 24 weeks
| Intervention | milliliter (mL) (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | 82.4 |
| Umeclidinium/Vilanterol | 169.6 |
The number of inhalations of rescue albuterol/salbutamol MDI was recorded in the participant ePRO in the morning and evening. Baseline is defined as the average of the non-missing values from the ePRO data collected in the last 7 days before the randomization (Day 1). a/s = albuterol/salbutamol. (NCT03162055)
Timeframe: From Baseline (Day -7) up to 24 weeks
| Intervention | puffs/day (Least Squares Mean) |
|---|---|
| Glycopyrronium/Formoterol Fumarate | -1.70 |
| Umeclidinium/Vilanterol | -2.35 |
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 32.6 |
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 2996.9 |
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 46.0 |
Maximum plasma concentration (Cmax) - Budesonide (NCT03250182)
Timeframe: Day 1
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 | 709.3 |
Maximum plasma concentration (Cmax) - Glycopyrronium (NCT03250182)
Timeframe: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 | 18.3 |
Maximum plasma concentration (Cmax) - Glycopyrronium (NCT03250182)
Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 | 17.2 |
Maximum plasma concentration (Cmax) - Formoterol (NCT03250182)
Timeframe: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 | 7.4 |
Time to maximum plasma concentration (tmax) - Budesonide (NCT03250182)
Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
| Intervention | hours (Median) | |
|---|---|---|
| Day 1 | Day 8 | |
| PT010 | 0.33 | 0.67 |
Maximum plasma concentration (Cmax) - Formoterol (NCT03250182)
Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 | 6.4 |
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 2407.3 |
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide (NCT03250182)
Timeframe: Day 8
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 3004.7 |
Maximum plasma concentration (Cmax) - Budesonide (NCT03250182)
Timeframe: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose
| Intervention | pg/mL (Geometric Mean) |
|---|---|
| PT010 | 663.2 |
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 61.2 |
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 39.4 |
Time to maximum plasma concentration (tmax) - Glycopyrronium (NCT03250182)
Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
| Intervention | hours (Median) | |
|---|---|---|
| Day 1 | Day 8 | |
| PT010 | 0.03 | 0.10 |
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol (NCT03250182)
Timeframe: Day 8
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 47.4 |
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 42.5 |
Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium (NCT03250182)
Timeframe: Day 8
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 73.9 |
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 2731.8 |
Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol (NCT03250182)
Timeframe: Day 1
| Intervention | h*pg/mL (Geometric Mean) |
|---|---|
| PT010 | 33.4 |
Time to maximum plasma concentration (tmax) - Formoterol (NCT03250182)
Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
| Intervention | hours (Median) | |
|---|---|---|
| Day 1 | Day 8 | |
| PT010 | 0.33 | 0.67 |
Area under the plasma concentration curve during the first dosing interval, tau (first dose). (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
| Intervention | pg*hour/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 85.45 | 20330 | 252.9 | 22.78 |
Average plasma concentration during a dosing interval, estimated as AUC(ss,tau)/12 (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | pg/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 14.07 | 2275 | 45.07 | 2.665 |
Apparent plasma clearance for parent drug estimated as dose divided by AUCss (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | L/hour (Mean) | |
|---|---|---|
| Aclidinium Bromide | Formoterol Fumarate | |
| AB/FF 400/12 BID | 3140 | 422.2 |
Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
| Intervention | pg*hour/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 78.61 | 20280 | 201.1 | 20.04 |
Terminal rate constant, estimated by log-linear least square regression of the terminal part of the concentration-time curve. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | 1/hours (Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 0.053 | 0.045 | 0.048 | 0.057 |
Assessment of the safety in terms of haematology parameters after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days. (NCT03276078)
Timeframe: Screening (Day -21) to Follow-up visit (Days 8-12)
| Intervention | Participants (Count of Participants) |
|---|---|
| AB/FF 400/12 BID | 0 |
Observed minimum concentration, taken directly from the individual concentration-time curve within a dosing interval on Day 5. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | pg/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 4.528 | 1032 | 22.88 | 1.281 |
Observed maximum concentration, taken directly from the individual concentration-time curve at steady state. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | pg/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 60.86 | 3691 | 81.02 | 6.465 |
Minimum plasma drug concentration at the end of the dosing interval (first dose), where possible. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
| Intervention | pg/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide Not calculable | LAS34850 | LAS34823 Not calculable | Formoterol Fumarate Not calculable | |
| AB/FF 400/12 BID | 0 | 627.7 | 0 | 0 |
Area under the plasma concentration curve during the dosing interval, tau at steady state. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | pg*hour/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 168.8 | 27300 | 540.9 | 31.98 |
Accumulation ratio for Cmax estimated as Css,max on Day 5/Cmax on Day 1 (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | ratio (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 1.297 | 1.185 | 2.070 | 1.384 |
Assessment of the safety in terms of the 12-lead ECG parameters after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days. (NCT03276078)
Timeframe: Screening (Day -21) to Follow-up visit (Days 8-12)
| Intervention | Participants (Count of Participants) |
|---|---|
| AB/FF 400/12 BID | 0 |
Apparent volume of distribution for parent drug at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | L (Mean) | |
|---|---|---|
| Aclidinium Bromide | Formoterol Fumarate | |
| AB/FF 400/12 BID | 81990 | 8284 |
Time to maximum concentration (h), taken directly from the individual concentration-time curve at steady state. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | hours (Median) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 0.08 | 3.00 | 0.50 | 0.08 |
Assessment of the safety in terms of urinalysis parameters after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days. (NCT03276078)
Timeframe: Screening (Day -21) to Follow-up visit (Days 8-12)
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| Urine protein present | Haematuria | |
| AB/FF 400/12 BID | 3 | 1 |
Time to maximum concentration (h), taken directly from the individual concentration-time curve (first dose). (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
| Intervention | hours (Median) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 0.08 | 3.00 | 1.75 | 1.00 |
Accumulation ratio for AUC(tau) estimated as AUC(ss,tau) on Day 5/AUC(tau) on Day 1 (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | ratio (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 1.966 | 1.355 | 2.157 | 1.436 |
"Accumulation ratio for Cmin estimated as Css,min on Day 5/Cmin on Day 1.~Additional parameters may be determined where appropriate." (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | ratio (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 1.877 | 1.641 | 2.601 | 1.822 |
Terminal half-life (h), estimated as (ln2)/λz. (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | hours (Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 19.42 | 20.95 | 17.34 | 14.06 |
Assessment of the safety in terms of serum biochemistry parameters (Alanine aminotransferase [ALT], Aspartate aminotransferase [AST], alkaline phosphatase [ALP], Gamma-glutamyl transferase [GGT], bilirubin, creatine kinase, lactate dehydrogenase, urea nitrogen, creatinine, urate, cholesterol, glucose, sodium, potassium, calcium, chloride, phosphate, protein, and albumin) after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days. (NCT03276078)
Timeframe: Screening (Day -21) to Follow-up visit (Days 8-12)
| Intervention | Participants (Count of Participants) |
|---|---|
| AB/FF 400/12 BID | 0 |
Fluctuation index during a dosing interval estimated as 100*(Cmax-Cmin)/Cav (%). (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours post the morning dose on Day 5
| Intervention | Percentage (Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 452.5 | 117.0 | 132.0 | 205.9 |
Assessment of the safety in terms of the incidences of AEs/SAEs after administration of Aclidinium Bromide/Formoterol Fumarate 400/12 μg BID for 5 days. (NCT03276078)
Timeframe: Screening (Day -21) to Follow-up visit (Days 8-12)
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| Any AE | Any SAE | |
| AB/FF 400/12 BID | 5 | 1 |
Observed maximum concentration, taken directly from the individual concentration-time curve (first dose). (NCT03276078)
Timeframe: Pre-dose and 5, 15, and 30 minutes, and 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post the morning dose on Day 1
| Intervention | pg/mL (Geometric Mean) | |||
|---|---|---|---|---|
| Aclidinium Bromide | LAS34850 | LAS34823 | Formoterol Fumarate | |
| AB/FF 400/12 BID | 45.82 | 3149 | 38.82 | 4.786 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478683)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.045 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.030 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period on Day 1. Weighted mean change from Baseline on Day 1 was calculated by subtracting weighted mean FEV1 on Day 1 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478683)
Timeframe: Baseline and Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.054 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.063 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. For Day 2 and Day 85, trough FEV1 was defined as the mean of the 23-hour and 24-hour serial spirometry FEV1 measurements. For Day 28 and Day 84, trough FEV1 was defined as the average of the pre-dose FEV1 measurements recorded before the morning dose of randomized study treatment. Change from Baseline in trough FEV1 was calculated by subtracting post-dose trough FEV1 value from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The treatment effect to be estimated for trough FEV1 was hypothetical effect if all participants stayed on their randomized study treatment. Only on treatment data was included in analysis. (NCT03478683)
Timeframe: Baseline, Days 2, 28, 84 and 85
| Intervention | Liters (Least Squares Mean) | |||
|---|---|---|---|---|
| Day 2, n=358,359 | Day 28, n=355,353 | Day 84, n=344,340 | Day 85, n=341,337 | |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.018 | -0.015 | -0.018 | -0.012 |
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.008 | 0.046 | 0.040 | 0.026 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478683)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.046 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.032 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. For Day 2 and Day 85, trough FEV1 was defined as the mean of the 23-hour and 24-hour serial spirometry FEV1 measurements. For Day 28 and Day 84, trough FEV1 was defined as the average of the pre-dose FEV1 measurements recorded before the morning dose of randomized study treatment. Change from Baseline in trough FEV1 was calculated by subtracting post-dose trough FEV1 value from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The treatment effect to be estimated for trough FEV1 was hypothetical effect if all participants stayed on their randomized study treatment. Only on treatment data was included in analysis. (NCT03478696)
Timeframe: Baseline, Days 2, 28, 84 and 85
| Intervention | Liters (Least Squares Mean) | |||
|---|---|---|---|---|
| Day 2, n=355,341 | Day 28, n=353,354 | Day 84, n=346,343 | Day 85, n=343,342 | |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | -0.010 | -0.019 | -0.030 | -0.022 |
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.015 | 0.044 | 0.024 | 0.029 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478696)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.039 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.029 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period on Day 1. Weighted mean change from Baseline on Day 1 was calculated by subtracting weighted mean FEV1 on Day 1 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478696)
Timeframe: Baseline and Day 1
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.045 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.041 |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post-dose) over 24-hour period at Week 12. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing (over 24-hour period) using the trapezoidal rule, and then dividing the value by the time interval (24-hour) over which the AUC was calculated. (NCT03478696)
Timeframe: Baseline and Week 12
| Intervention | Liters (Least Squares Mean) |
|---|---|
| Fluticasone Furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | 0.040 |
| Budesonide/Formoterol 320/9 mcg Plus Tiotropium 18 mcg | 0.023 |
Clinically relevant changes identified based on change from baseline. (NCT03573817)
Timeframe: Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
| Intervention | Participants (Count of Participants) |
|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | 0 |
| Period 2: Revefenacin + Formoterol (Combo Solution) | 0 |
| Period 1: Placebo + Formoterol (Sequential) | 0 |
| Period 2: Placebo + Formoterol (Combo Solution) | 0 |
Clinically significant changes identified based on change from baseline. Vital signs measured included heart rate, systolic blood pressure and diastolic blood pressure. (NCT03573817)
Timeframe: Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
| Intervention | Participants (Count of Participants) |
|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | 0 |
| Period 2: Revefenacin + Formoterol (Combo Solution) | 0 |
| Period 1: Placebo + Formoterol (Sequential) | 0 |
| Period 2: Placebo + Formoterol (Combo Solution) | 0 |
Clinically relevant changes identified based on change from baseline. Laboratory Measures assessed included hematology and serum. (NCT03573817)
Timeframe: Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
| Intervention | Participants (Count of Participants) |
|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | 0 |
| Period 2: Revefenacin + Formoterol (Combo Solution) | 0 |
| Period 1: Placebo + Formoterol (Sequential) | 0 |
| Period 2: Placebo + Formoterol (Combo Solution) | 0 |
An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurred after the participant has received the study drug. (NCT03573817)
Timeframe: Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
| Intervention | Participants (Count of Participants) |
|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | 7 |
| Period 2: Revefenacin + Formoterol (Combo Solution) | 6 |
| Period 1: Placebo + Formoterol (Sequential) | 3 |
| Period 2: Placebo + Formoterol (Combo Solution) | 5 |
"A serious adverse event (SAE) was defined as any untoward medical occurrence occurring at any dose that resulted in any of the following outcomes:~Death~Life-threatening situation. Life-threatening refers to a situation in which the participant was at risk of death at the time of the event; it does not refer to an event which might have caused death if it were more severe~Inpatient hospitalization or prolongation of existing hospitalization~Congenital anomaly in the offspring of a participant who received study drug~Important medical events that may not result in death, be immediately life-threatening, or require hospitalization, could have been considered an SAE when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition~A treatment-emergent SAE is an SAE that occurred after the participant has received the study drug." (NCT03573817)
Timeframe: Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)
| Intervention | Participants (Count of Participants) |
|---|---|
| Period 1: Revefenacin + Formoterol (Sequential) | 0 |
| Period 2: Revefenacin + Formoterol (Combo Solution) | 0 |
| Period 1: Placebo + Formoterol (Sequential) | 0 |
| Period 2: Placebo + Formoterol (Combo Solution) | 0 |
Adherence was measured using the Propeller Health Inhaler monitor and web-based software management platform that tracks adherence of asthma medications. The change in adherence was calculated between V1 (baseline) to V3 (12 Months). (NCT04179461)
Timeframe: Baseline to 12 months
| Intervention | percentage of medication taken (Median) | |
|---|---|---|
| V1 | V3 | |
| Personalized Treatment | 42 | 36 |
"ACT was measured by questionnaire, assessing frequency of reported asthma symptoms, rescue medication use, the effect of asthma on daily functioning, and overall asthma control. The change in ACT score was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months).~[The ACT score has a minimum value = 5, maximum value = 25, a score 19 indicates well-controlled asthma]" (NCT04179461)
Timeframe: Baseline to 12 months
| Intervention | score on a scale (Median) | ||
|---|---|---|---|
| V1 | V2 | V3 | |
| Personalized Treatment | 23.0 | 21.7 | 22.5 |
"FEV1 is air volume exhaled in 1 second during spirometry. Forced vital capacity is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. The change in FEV1/FVC was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months). This will be used as a measurement in asthma severity.~[A lower FEV1/FVC ratio indicates more severe asthma]" (NCT04179461)
Timeframe: Baseline to 12 months
| Intervention | Ratio (Median) | ||
|---|---|---|---|
| V1 | V2 | V3 | |
| Personalized Treatment | 0.81 | 0.8 | 0.8 |
"CASI was measured by questionnaire and is a severity score of symptom burden, exacerbations, healthcare utilization, lung function and dose of inhaled corticosteroids. The change in CASI score was calculated between V1 (Baseline), V2 (Guideline Care - before intervention), and V3 (12 Months).~[The CASI score has a minimum value = 0, maximum value = 20, a higher score indicates greater asthma severity]" (NCT04179461)
Timeframe: Baseline to 12 months
| Intervention | score on a scale (Median) | ||
|---|---|---|---|
| V1 | V2 | V3 | |
| Personalized Treatment | 5 | 5 | 5 |
| Substance | Relationship Strength | Studies | Trials | Classes | Roles |
|---|---|---|---|---|---|
| gamma-aminobutyric acid gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.. gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4. | 2.03 | 1 | 0 | amino acid zwitterion; gamma-amino acid; monocarboxylic acid | human metabolite; neurotransmitter; Saccharomyces cerevisiae metabolite; signalling molecule |
| acetamide acetimidic acid : A carboximidic acid that is acetic acid in which the carbonyl oxygen is replaced by an imino group. | 2.03 | 1 | 0 | acetamides; carboximidic acid; monocarboxylic acid amide; N-acylammonia | |
| quinacrine Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.. quinacrine : A member of the class of acridines that is acridine substituted by a chloro group at position 6, a methoxy group at position 2 and a [5-(diethylamino)pentan-2-yl]nitrilo group at position 9. | 2.03 | 1 | 0 | acridines; aromatic ether; organochlorine compound; tertiary amino compound | antimalarial; EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor |
| catechol [no description available] | 2.44 | 2 | 0 | catechols | allelochemical; genotoxin; plant metabolite |
| taxifolin [no description available] | 2.44 | 2 | 0 | 3'-hydroxyflavanones; 4'-hydroxyflavanones; dihydroflavonols; pentahydroxyflavanone; secondary alpha-hydroxy ketone | |
| phosphonoacetic acid Phosphonoacetic Acid: A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.. phosphonoacetic acid : A member of the class of phosphonic acids that is phosphonic acid in which the hydrogen attached to the phosphorous is replaced by a carboxymethyl group. | 2.44 | 2 | 0 | monocarboxylic acid; phosphonic acids | antiviral agent; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor |
| 3,4-dihydroxyphenylacetic acid 3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.. (3,4-dihydroxyphenyl)acetic acid : A dihydroxyphenylacetic acid having the two hydroxy substituents located at the 3- and 4-positions. It is a metabolite of dopamine.. dihydroxyphenylacetic acid : A dihydroxy monocarboxylic acid consisting of phenylacetic acid having two phenolic hydroxy substituents. | 2.44 | 2 | 0 | catechols; dihydroxyphenylacetic acid | human metabolite |
| aminocaproic acid Aminocaproic Acid: An antifibrinolytic agent that acts by inhibiting plasminogen activators which have fibrinolytic properties.. 6-aminohexanoic acid : An epsilon-amino acid comprising hexanoic acid carrying an amino substituent at position C-6. Used to control postoperative bleeding, and to treat overdose effects of the thrombolytic agents streptokinase and tissue plasminogen activator. | 2.03 | 1 | 0 | amino acid zwitterion; epsilon-amino acid; omega-amino fatty acid | antifibrinolytic drug; hematologic agent; metabolite |
| diacetyl butane-2,3-dione : An alpha-diketone that is butane substituted by oxo groups at positions 2 and 3. It is a metabolite produced during the malolactic fermentation. | 2.03 | 1 | 0 | alpha-diketone | Escherichia coli metabolite; Saccharomyces cerevisiae metabolite |
| hydroquinone [no description available] | 2.44 | 2 | 0 | benzenediol; hydroquinones | antioxidant; carcinogenic agent; cofactor; Escherichia coli metabolite; human xenobiotic metabolite; mouse metabolite; skin lightening agent |
| melatonin [no description available] | 2.03 | 1 | 0 | acetamides; tryptamines | anticonvulsant; central nervous system depressant; geroprotector; hormone; human metabolite; immunological adjuvant; mouse metabolite; radical scavenger |
| n-acetylserotonin N-acetylserotonin : An N-acylserotonin resulting from the formal condensation of the primary amino group of serotonin with the carboxy group of acetic acid. | 2.03 | 1 | 0 | acetamides; N-acylserotonin; phenols | antioxidant; human metabolite; mouse metabolite; tropomyosin-related kinase B receptor agonist |
| pyrazinamide pyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis. | 2.03 | 1 | 0 | monocarboxylic acid amide; N-acylammonia; pyrazines | antitubercular agent; prodrug |
| quinolinic acid Quinolinic Acid: A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.. pyridinedicarboxylic acid : Any member of the class of pyridines carrying two carboxy groups.. quinolinic acid : A pyridinedicarboxylic acid that is pyridine substituted by carboxy groups at positions 2 and 3. It is a metabolite of tryptophan. | 2.03 | 1 | 0 | pyridinedicarboxylic acid | Escherichia coli metabolite; human metabolite; mouse metabolite; NMDA receptor agonist |
| taurine [no description available] | 2.03 | 1 | 0 | amino sulfonic acid; zwitterion | antioxidant; Escherichia coli metabolite; glycine receptor agonist; human metabolite; mouse metabolite; nutrient; radical scavenger; Saccharomyces cerevisiae metabolite |
| 2-amino-5-phosphonovalerate 2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors. | 2.03 | 1 | 0 | non-proteinogenic alpha-amino acid | NMDA receptor antagonist |
| alpha-methyl-4-carboxyphenylglycine [no description available] | 2.03 | 1 | 0 | ||
| 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid: structure given in first source; NMDA receptor antagonist | 2.03 | 1 | 0 | ||
| 1-hydroxy-3-amino-2-pyrrolidone 1-hydroxy-3-amino-2-pyrrolidone: a CNS depressant; structure in first source | 2.03 | 1 | 0 | ||
| ibotenic acid Ibotenic Acid: A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. | 2.03 | 1 | 0 | non-proteinogenic alpha-amino acid | neurotoxin |
| n(8)-bromoacetyl-n(1)-3'-(4-indolyloxy)-2'-hydroxypropyl-1,8-diamino-4-menthane N(8)-bromoacetyl-N(1)-3'-(4-indolyloxy)-2'-hydroxypropyl-1,8-diamino-4-menthane: structure given in first source | 2.03 | 1 | 0 | ||
| sk&f-38393 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine: A selective D1 dopamine receptor agonist used primarily as a research tool.. 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol : A benzazepine that is 2,3,4,5-tetrahydro-3-benzazepine bearing a phenyl substituent at position 1 and two hydroxy substituents at positions 7 and 8.. SKF 38393 : A racemate comprising equimolar amounts of (R)- and (S)-SKF 38393 | 2.44 | 2 | 0 | benzazepine; catechols; secondary amino compound | |
| vanilmandelic acid Vanilmandelic Acid: A 3-O-methyl ether of 3,4-dihydroxymandelic acid. It is an end-stage metabolite of CATECHOLAMINES; EPINEPHRINE; and NOREPINEPHRINE.. vanillylmandelic acid : An aromatic ether that is the 3-O-methyl ether of 3,4-dihydroxymandelic acid. | 2.03 | 1 | 0 | 2-hydroxy monocarboxylic acid; aromatic ether; phenols | human metabolite |
| 1,10-diaminodecane [no description available] | 2.44 | 2 | 0 | ||
| 1,3-diethyl-8-phenylxanthine 1,3-diethyl-8-phenylxanthine: structure given in first source | 2.03 | 1 | 0 | ||
| 1,3-dipropyl-8-cyclopentylxanthine DPCPX : An oxopurine that is 7H-xanthine substituted at positions 1 and 3 by propyl groups and at position 8 by a cyclohexyl group. | 2.44 | 2 | 0 | oxopurine | adenosine A1 receptor antagonist; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor |
| 1,3-dipropyl-8-(4-sulfophenyl)xanthine 1,3-dipropyl-8-(4-sulfophenyl)xanthine: adenosine receptor antagonist | 2.03 | 1 | 0 | ||
| 1,5-dihydroxyisoquinoline 1,5-dihydroxyisoquinoline: structure in first source. isoquinoline-1,5-diol : An isoquinolinol that is isoquinoline in which the hydrogens at positions 1 and 5 are replaced by hydroxy groups. | 2.03 | 1 | 0 | isoquinolinol | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| pk 11195 PK-11195 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 1-(2-chlorophenyl)isoquinoline-3-carboxylic acid with the amino group of sec-butylmethylamine | 2.44 | 2 | 0 | aromatic amide; isoquinolines; monocarboxylic acid amide; monochlorobenzenes | antineoplastic agent |
| 1-(2-trifluoromethylphenyl)imidazole 1-(2-trifluoromethylphenyl)imidazole: an inhibitor of neuronal nitric oxide synthase in mouse | 2.03 | 1 | 0 | imidazoles | |
| 1-aminobenzotriazole [no description available] | 2.44 | 2 | 0 | ||
| 1-methylimidazole 1-methyl-1H-imidazole : A 1H-imidazole having a methyl substituent at the N-1 position. | 2.03 | 1 | 0 | imidazoles | |
| edelfosine edelfosine: RN given refers to parent cpd. edelfosine : A racemate comprising equimolar amounts of (R)- and (S)-edelfosine.. 1-octadecyl-2-methylglycero-3-phosphocholine : A glycerophosphocholine that is glycero-3-phosphocholine substituted at positions 1 and 2 by octadecyl and methyl groups respectively. | 2.03 | 1 | 0 | glycerophosphocholine | |
| 1h-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one: structure given in first source; inhibits guanylyl cyclase. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one : A member of the class of oxadiazoloquinoxalines that is 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline substituted at position 1 by an oxo group. | 2.44 | 2 | 0 | oxadiazoloquinoxaline | EC 4.6.1.2 (guanylate cyclase) inhibitor |
| 2,2'-dipyridyl 2,2'-Dipyridyl: A reagent used for the determination of iron.. 2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'. | 2.44 | 2 | 0 | bipyridine | chelator; ferroptosis inhibitor |
| 2-hydroxysaclofen 2-hydroxysaclofen: structure given in first source | 2.03 | 1 | 0 | organochlorine compound | |
| 3,4-dichloroisocoumarin 3,4-dichloroisocoumarin : A member of the class of isocoumarins that is isocoumarin substituted by chloro groups at positions 3 and 4. It is a serine protease inhibitor. | 2.44 | 2 | 0 | isocoumarins; organochlorine compound | geroprotector; serine protease inhibitor |
| phaclofen phaclofen: peripheral & central baclofen & GABA antagonist; structure given in first source | 2.03 | 1 | 0 | organophosphate oxoanion; zwitterion | |
| 3-aminobenzamide [no description available] | 2.03 | 1 | 0 | benzamides; substituted aniline | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| 3-bromo-7-nitroindazole [no description available] | 2.03 | 1 | 0 | ||
| enprofylline enprofylline : Xanthine bearing a propyl substituent at position 3. A bronchodilator, it is used for the symptomatic treatment of asthma and chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy. | 2.03 | 1 | 0 | oxopurine | anti-arrhythmia drug; anti-asthmatic drug; bronchodilator agent; non-steroidal anti-inflammatory drug |
| 3-nitropropionic acid 3-nitropropionic acid: succinate dehydrogenase inactivator; biosynthesized by FABACEAE plants from ASPARAGINE. 3-nitropropanoic acid : A C-nitro compound that is propanoic acid in which one of the methyl hydrogens has been replaced by a nitro group. | 2.03 | 1 | 0 | C-nitro compound | antimycobacterial drug; EC 1.3.5.1 [succinate dehydrogenase (quinone)] inhibitor; mycotoxin; neurotoxin |
| cgp 52411 4,5-dianilinophthalimide: structure given in first source. 4,5-dianilinophthalimide : Phthalimide substituted at the 4- and 5-positions by anilino groups. | 2.05 | 1 | 0 | phthalimides | geroprotector; tyrosine kinase inhibitor |
| 4-amino-1,8-naphthalimide 4-amino-1,8-naphthalimide: inhibits ADP-ribosylation; sometimes abreviated as 4-AN; | 2.44 | 2 | 0 | benzoisoquinoline; dicarboximide | |
| 4-aminopyridine [no description available] | 2.03 | 1 | 0 | aminopyridine; aromatic amine | avicide; orphan drug; potassium channel blocker |
| homovanillic acid Homovanillic Acid: A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.. homovanillate : A hydroxy monocarboxylic acid anion which is obtained by deprotonation of the carboxy group of homovanillic acid.. homovanillic acid : A monocarboxylic acid that is the 3-O-methyl ether of (3,4-dihydroxyphenyl)acetic acid. It is a catecholamine metabolite. | 2.44 | 2 | 0 | guaiacols; monocarboxylic acid | human metabolite; mouse metabolite |
| 4-hydroxybenzoic acid hydrazide 4-hydroxybenzoic acid hydrazide: metabolite of nifuroxazide. 4-hydroxybenzohydrazide : A carbohydrazide obtained by formal condensation of the carboxy group of 4-hydroxybenzoic acid with hydrazine. | 2.03 | 1 | 0 | carbohydrazide; phenols | |
| 4-phenyl-3-furoxancarbonitrile 4-phenyl-3-furoxancarbonitrile: structure given in first source. 4-phenyl-3-furoxancarbonitrile : A 1,2,5-oxadiazole substituted by an oxido, cyano and phenyl groups at positions 2, 3 and 4, respectively. It is a vasodilator and inhibitor of platelet aggregation. | 2.44 | 2 | 0 | 1,2,5-oxadiazole; benzenes; N-oxide; nitrile | geroprotector; nitric oxide donor; platelet aggregation inhibitor; soluble guanylate cyclase activator; vasodilator agent |
| 5,5-dimethyl-1-pyrroline-1-oxide 5,5-dimethyl-1-pyrroline-1-oxide: do not confuse with DMPO (4',5'-dihydroxy-7-methoxy-4-phenyl-5,2'-oxidocoumarin). 5,5-dimethyl-1-pyrroline N-oxide : A member of the class of 1-pyrroline nitrones (1-pyrroline N-oxides) resulting from the formal N-oxidation of 5,5-dimethyl-1-pyrroline. Used as a spin trap for the study of radicals formed by enzymatic acetaldehyde oxidation. | 2.03 | 1 | 0 | 1-pyrroline nitrones | neuroprotective agent; spin trapping reagent |
| phenytoin [no description available] | 2.03 | 1 | 0 | imidazolidine-2,4-dione | anticonvulsant; drug allergen; sodium channel blocker; teratogenic agent |
| 5,7-dichlorokynurenic acid 5,7-dichlorokynurenic acid: potent antagonist at the N-methyl-D-aspartate receptor-associated glycine binding site | 2.03 | 1 | 0 | quinolines | |
| 5-(n,n-hexamethylene)amiloride 5-(N,N-hexamethylene)amiloride: inhibitor of Na+-H+ exchange; has anti-HIV-1 activity. 5-(N,N-hexamethylene)amiloride : A member of the class of pyrazines that is amiloride in which the two amino hydrogens at position N-5 are replaced by a hexamethylene moiety, resulting in the formation of an azepane ring. | 2.44 | 2 | 0 | aromatic amine; azepanes; guanidines; monocarboxylic acid amide; organochlorine compound; pyrazines | antineoplastic agent; apoptosis inducer; odorant receptor antagonist; sodium channel blocker |
| ethylisopropylamiloride ethylisopropylamiloride: structure in first source. ethylisopropylamiloride : A member of the class of pyrazines that is amiloride in which the amino substitutent of the pyrazine ring that is adjacent to the chloro substituent has been substituted by an ethyl group and by an isopropyl group. | 2.44 | 2 | 0 | aromatic amine; guanidines; monocarboxylic acid amide; organochlorine compound; pyrazines; tertiary amino compound | anti-arrhythmia drug; neuroprotective agent; sodium channel blocker |
| 5-fluoroindole-2-carboxylic acid 5-fluoroindole-2-carboxylic acid: N-methyl-D-aspartate receptor antagonist | 2.44 | 2 | 0 | indolyl carboxylic acid | |
| hydroxyindoleacetic acid (5-hydroxyindol-3-yl)acetic acid : A member of the class of indole-3-acetic acids that is indole-3-acetic acid substituted by a hydroxy group at C-5. | 2.03 | 1 | 0 | indole-3-acetic acids | drug metabolite; human metabolite; mouse metabolite |
| phenanthridone phenanthridone: coal tar derivative; structure given in first source. phenanthridone : A member of the class of phenanthridines that is phenanthridine with an oxo substituent at position 6. A poly(ADP-ribose) polymerase (PARP) inhibitor, it has been shown to exhibit immunosuppressive activity. | 2.44 | 2 | 0 | lactam; phenanthridines | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; immunosuppressive agent; mutagen |
| 6-chloromelatonin [no description available] | 2.03 | 1 | 0 | acetamides | |
| 6-hydroxymelatonin 6-hydroxymelatonin : A member of the class of tryptamines that is melatonin with a hydroxy group substituent at position 6. | 2.03 | 1 | 0 | acetamides; tryptamines | metabolite; mouse metabolite |
| 6-methoxytryptoline 6-methoxytryptoline: RN given refers to parent cpd; structure | 2.03 | 1 | 0 | ||
| 6-nitroso-1,2-benzopyrone [no description available] | 2.44 | 2 | 0 | ||
| 7-chlorokynurenic acid 7-chlorokynurenic acid: selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex; structure given in first source. 7-chlorokynurenic acid : A quinolinemonocarboxylic acid that is quinaldic acid which is substituted by a hydroxy group at position 4 and by a chlorine at position 7. It is a potent NMDA glutamate receptor antagonist which antagonizes the strychnine-insensitive glycine site of the NMDA receptor. It also prevents neurodegeneration produced by quinolinic acid. | 2.03 | 1 | 0 | organochlorine compound; quinolinemonocarboxylic acid | neuroprotective agent; NMDA receptor antagonist |
| 7-nitroindazole 7-nitroindazole: an inhibitor of nitric oxide synthase; exhibits anti-nociceptive activity without increasing blood pressure | 2.03 | 1 | 0 | ||
| 8-(4-sulfophenyl)theophylline 8-(4-sulfophenyl)theophylline: adenosine antagonist | 2.44 | 2 | 0 | ||
| 8-cyclopentyl-1,3-dimethylxanthine 8-cyclopentyl-1,3-dimethylxanthine: prolongs epileptic seizures in rats | 2.03 | 1 | 0 | oxopurine | |
| 8-phenyltheophylline 8-phenyltheophylline: purinergic P1 receptor antagonist | 2.03 | 1 | 0 | ||
| aa 861 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone: structure given in first source. docebenone : A member of the class of benzoquinones that is p-benzoquinone in which the hydrogens are substituted by three methyl groups and a 12-hydroxydodeca-5,10-diyn-1-yl group. | 2.05 | 1 | 0 | 1,4-benzoquinones; acetylenic compound; primary alcohol | EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor; ferroptosis inhibitor |
| acetazolamide Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337) | 2.03 | 1 | 0 | monocarboxylic acid amide; sulfonamide; thiadiazoles | anticonvulsant; diuretic; EC 4.2.1.1 (carbonic anhydrase) inhibitor |
| acetohexamide Acetohexamide: A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide.. acetohexamide : An N-sulfonylurea that is urea in which a hydrogen attached to one of the nitrogens is replaced by a p-acetylphenylsulfonyl group, while a hydrogen attached to the other nitrogen is replaced by a cyclohexyl group. | 2.03 | 1 | 0 | acetophenones; N-sulfonylurea | hypoglycemic agent; insulin secretagogue |
| ag 127 tyrphostin AG 126: inhibits development of postoperative ileus induced by surgical manipulation of murine colon | 2.44 | 2 | 0 | nitrophenol | |
| rtki cpd [no description available] | 2.44 | 2 | 0 | aromatic ether; monochlorobenzenes; quinazolines | antineoplastic agent; antiviral agent; epidermal growth factor receptor antagonist; geroprotector |
| tyrphostin a23 tyrphostin A23: inhibits EGF-stimulated thymidine incorporation as well as EGF-stimulated receptor autophosphorylation & tyrosine phosphorylation & cell proliferation; structure given in first source | 2.44 | 2 | 0 | catechols | |
| tyrphostin 25 [no description available] | 2.44 | 2 | 0 | benzenetriol | |
| tyrphostin a1 [no description available] | 2.03 | 1 | 0 | methoxybenzenes | geroprotector |
| 1-aminoindan-1,5-dicarboxylic acid 1-aminoindan-1,5-dicarboxylic acid: structure given in first source | 2.03 | 1 | 0 | ||
| albuterol Albuterol: A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.. albuterol : A member of the class of phenylethanolamines that is 4-(2-amino-1-hydroxyethyl)-2-(hydroxymethyl)phenol having a tert-butyl group attached to the nirogen atom. It acts as a beta-adrenergic agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). | 2.97 | 4 | 0 | phenols; phenylethanolamines; secondary amino compound | beta-adrenergic agonist; bronchodilator agent; environmental contaminant; xenobiotic |
| alpha-methyltyrosine methyl ester alpha-methyltyrosine methyl ester: RN given refers to parent cpd | 2.03 | 1 | 0 | ||
| altretamine Altretamine: A hexamethyl-2,4,6-triamine derivative of 1,3,5-triazine. | 2.03 | 1 | 0 | triamino-1,3,5-triazine | |
| amfonelic acid amfonelic acid: CNS-stimulant | 2.03 | 1 | 0 | ||
| amifostine anhydrous Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.. amifostine : An organic thiophosphate that is the S-phospho derivative of 2-[(3-aminopropyl)amino]ethanethiol. A prodrug for the free thiol, WR-1065, which is used as a cytoprotectant in cancer chemotherapy and radiotherapy. | 2.03 | 1 | 0 | diamine; organic thiophosphate | antioxidant; prodrug; radiation protective agent |
| theophylline [no description available] | 2.03 | 1 | 0 | dimethylxanthine | adenosine receptor antagonist; anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; drug metabolite; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; fungal metabolite; human blood serum metabolite; immunomodulator; muscle relaxant; vasodilator agent |
| amoxapine Amoxapine: The N-demethylated derivative of the antipsychotic agent LOXAPINE that works by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used for the treatment of depression.. amoxapine : A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position. | 2.44 | 2 | 0 | dibenzooxazepine | adrenergic uptake inhibitor; antidepressant; dopaminergic antagonist; geroprotector; serotonin uptake inhibitor |
| aniracetam [no description available] | 2.03 | 1 | 0 | N-acylpyrrolidine; pyrrolidin-2-ones | |
| 2-amino-4-phosphonobutyric acid 2-amino-4-phosphonobutyric acid: glutamate antagonist in locust muscle; structure; do not confuse with L-AP4, which is the propionic acid version | 2.03 | 1 | 0 | ||
| aspirin Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5). acetylsalicylate : A benzoate that is the conjugate base of acetylsalicylic acid, arising from deprotonation of the carboxy group.. acetylsalicylic acid : A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with cyclooxygenase inhibitor activity. | 2.03 | 1 | 0 | benzoic acids; phenyl acetates; salicylates | anticoagulant; antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; EC 1.1.1.188 (prostaglandin-F synthase) inhibitor; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug; plant activator; platelet aggregation inhibitor; prostaglandin antagonist; teratogenic agent |
| atenolol Atenolol: A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.. atenolol : An ethanolamine compound having a (4-carbamoylmethylphenoxy)methyl group at the 1-position and an N-isopropyl substituent. | 2.03 | 1 | 0 | ethanolamines; monocarboxylic acid amide; propanolamine | anti-arrhythmia drug; antihypertensive agent; beta-adrenergic antagonist; environmental contaminant; sympatholytic agent; xenobiotic |
| alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate: a glutamate agonist | 2.03 | 1 | 0 | alpha-amino acid | |
| aurintricarboxylic acid Aurintricarboxylic Acid: A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues.. aurintricarboxylic acid : A member of the class of quinomethanes that is 3-methylidene-6-oxocyclohexa-1,4-diene-1-carboxylic acid in which the methylidene hydrogens are replaced by 4-carboxy-3-hydroxyphenyl groups. The trisodium salt is the biological stain 'chrome violet CG' while the triammonium salt is 'aluminon'. | 2.44 | 2 | 0 | monohydroxybenzoic acid; quinomethanes; tricarboxylic acid | fluorochrome; histological dye; insulin-like growth factor receptor 1 antagonist |
| azathioprine Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed). azathioprine : A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS. | 2.44 | 2 | 0 | aryl sulfide; C-nitro compound; imidazoles; thiopurine | antimetabolite; antineoplastic agent; carcinogenic agent; DNA synthesis inhibitor; hepatotoxic agent; immunosuppressive agent; prodrug |
| azelaic acid nonanedioic acid : An alpha,omega-dicarboxylic acid that is heptane substituted at positions 1 and 7 by carboxy groups. | 2.03 | 1 | 0 | alpha,omega-dicarboxylic acid; dicarboxylic fatty acid | antibacterial agent; antineoplastic agent; dermatologic drug; plant metabolite |
| baclofen [no description available] | 2.03 | 1 | 0 | amino acid zwitterion; gamma-amino acid; monocarboxylic acid; monochlorobenzenes; primary amino compound | central nervous system depressant; GABA agonist; muscle relaxant |
| bay-k-8644 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester: A dihydropyridine derivative, which, in contrast to NIFEDIPINE, functions as a calcium channel agonist. The compound facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels, thereby causing vasoconstrictor and positive inotropic effects. It is used primarily as a research tool.. Bay-K-8644 : A racemate comprising equimolar amounts of (R)- and (S)-Bay-K-8644. methyl 2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylate : A pentasubstituted dihydropyridine carrying methoxycarbonyl, 2-(trifluoromethyl)phenyl and nitro substituents at positions 3, 4 and 5 respectively as well as two methyl substituents at positions 2 and 6. | 2.44 | 2 | 0 | (trifluoromethyl)benzenes; C-nitro compound; dihydropyridine; methyl ester | |
| benzamide benzamide : An aromatic amide that consists of benzene bearing a single carboxamido substituent. The parent of the class of benzamides. | 2.03 | 1 | 0 | benzamides | |
| bepridil Bepridil: A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist.. bepridil : A tertiary amine in which the substituents on nitrogen are benzyl, phenyl and 3-(2-methylpropoxy)-2-(pyrrolidin-1-yl)propyl. | 2.03 | 1 | 0 | pyrrolidines; tertiary amine | anti-arrhythmia drug; antihypertensive agent; calcium channel blocker; vasodilator agent |
| bml 190 indomethacin morpholinylamide: an inverse agonist of the cannabinoid CB2 receptor | 2.44 | 2 | 0 | N-acylindole | |
| brimonidine [no description available] | 2.44 | 2 | 0 | imidazoles; quinoxaline derivative; secondary amine | adrenergic agonist; alpha-adrenergic agonist; antihypertensive agent |
| bu 224 BU 224: a selective imidazoline 2-receptor blocker | 2.05 | 1 | 0 | quinolines | |
| bumetanide [no description available] | 2.03 | 1 | 0 | amino acid; benzoic acids; sulfonamide | diuretic; EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor |
| caffeine [no description available] | 2.03 | 1 | 0 | purine alkaloid; trimethylxanthine | adenosine A2A receptor antagonist; adenosine receptor antagonist; adjuvant; central nervous system stimulant; diuretic; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; environmental contaminant; food additive; fungal metabolite; geroprotector; human blood serum metabolite; mouse metabolite; mutagen; plant metabolite; psychotropic drug; ryanodine receptor agonist; xenobiotic |
| carbamazepine Carbamazepine: A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties.. carbamazepine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine carrying a carbamoyl substituent at the azepine nitrogen, used as an anticonvulsant. | 2.03 | 1 | 0 | dibenzoazepine; ureas | analgesic; anticonvulsant; antimanic drug; drug allergen; EC 3.5.1.98 (histone deacetylase) inhibitor; environmental contaminant; glutamate transporter activator; mitogen; non-narcotic analgesic; sodium channel blocker; xenobiotic |
| carbetapentane carbetapentane: RN given refers to parent cpd | 2.03 | 1 | 0 | benzenes | |
| carisoprodol Carisoprodol: A centrally acting skeletal muscle relaxant whose mechanism of action is not completely understood but may be related to its sedative actions. It is used as an adjunct in the symptomatic treatment of musculoskeletal conditions associated with painful muscle spasm. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1202). carisoprodol : A carbamate ester that is the mono-N-isopropyl derivative of meprobamate (which is a significant metabolite). Carisoprodol interrupts neuronal communication within the reticular formation and spinal cord, resulting in sedation and alteration in pain perception. It is used as a muscle relaxant in the symptomatic treatment of musculoskeletal conditions associated with painful muscle spasm. | 2.03 | 1 | 0 | carbamate ester | muscle relaxant |
| carmustine Carmustine: A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed). carmustine : A member of the class of N-nitrosoureas that is 1,3-bis(2-chloroethyl)urea in which one of the nitrogens is substituted by a nitroso group. | 2.03 | 1 | 0 | N-nitrosoureas; organochlorine compound | alkylating agent; antineoplastic agent |
| cgs 12066 4-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline : A pyrroloquinoxaline that is pyrrolo[1,2-a]quinoxaline bearing additional 4-methylpiperazin-1-yl and trifluoromethyl substituents at positions 4 and 7 respectively. A 5-hydroxytryptamine receptor 1B (5-HT1B) full agonist, 10-fold selective over 5-HT1A and 1000-fold selective over 5-HT2C receptors. Centrally active following systemic administration. | 2.03 | 1 | 0 | N-arylpiperazine; organofluorine compound; pyrroloquinoxaline | serotonergic agonist |
| cgs 15943 9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine: non-xanthine triazoloquinazoline adenosine antagonist. CGS 15943 : A member of the class of triazoloquinazolines that is [1,2,4]triazolo[1,5-c]quinazoline substited at positions 2, 5 and 9 by furan-2-yl, amino and chloro groups respectively. A potent antagonist at adenosine A1 and adenosine A2A receptors. | 2.44 | 2 | 0 | aromatic amine; biaryl; furans; organochlorine compound; primary amino compound; quinazolines; triazoloquinazoline | adenosine A1 receptor antagonist; adenosine A2A receptor antagonist; antineoplastic agent; central nervous system stimulant |
| chlorambucil Chlorambucil: A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed). chlorambucil : A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia. | 2.44 | 2 | 0 | aromatic amine; monocarboxylic acid; nitrogen mustard; organochlorine compound; tertiary amino compound | alkylating agent; antineoplastic agent; carcinogenic agent; drug allergen; immunosuppressive agent |
| chlormezanone Chlormezanone: A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm.. chlormezanone : A 1,3-thiazine that is 1,3-thiazinan-4-one S,S-dioxide in which a hydrogen at position 2 is substituted by a 4-chlorophenyl group and the hydrogen attached to the nitrogen is substituted by methyl. A non-benzodiazepine muscle relaxant, it was used in the management of anxiety and in the treatment of muscle spasms until being discontinued worldwide by its manufacturer in 1996, due to rare but serious cutaneous reactions. | 2.03 | 1 | 0 | 1,3-thiazine; lactam; monochlorobenzenes; sulfone | antipsychotic agent; anxiolytic drug; muscle relaxant |
| chloroquine Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. chloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis. | 2.05 | 1 | 0 | aminoquinoline; organochlorine compound; secondary amino compound; tertiary amino compound | anticoronaviral agent; antimalarial; antirheumatic drug; autophagy inhibitor; dermatologic drug |
| chlorothiazide Chlorothiazide: A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812). thiazide : Heterocyclic compound with sulfur and nitrogen in the ring.. chlorothiazide : 4H-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position is substituted by chlorine and that at position 7 is substituted by a sulfonamide group. A diuretic, it is used for treatment of oedema and hypertension. | 2.03 | 1 | 0 | benzothiadiazine | antihypertensive agent; diuretic |
| chlorpropamide Chlorpropamide: A sulfonylurea hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. (From Martindale, The Extra Pharmacopoeia, 30th ed, p277). chlorpropamide : An N-sulfonylurea that is urea in which a hydrogen attached to one of the nitrogens is substituted by 4-chlorobenzenesulfonyl group and a hydrogen attached to the other nitrogen is substituted by propyl group. Chlorpropamide is a hypoglycaemic agent used in the treatment of type 2 (non-insulin-dependent) diabetes mellitus not responding to dietary modification. | 2.03 | 1 | 0 | monochlorobenzenes; N-sulfonylurea | hypoglycemic agent; insulin secretagogue |
| chlorzoxazone Chlorzoxazone: A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202). chlorzoxazone : A member of the class of 1,3-benzoxazoles that is 1,3-benzoxazol-2-ol in which the hydrogen atom at position 5 is substituted by chlorine. A centrally acting muscle relaxant with sedative properties, it is used for the symptomatic treatment of painful muscle spasm. | 2.03 | 1 | 0 | 1,3-benzoxazoles; heteroaryl hydroxy compound; organochlorine compound | muscle relaxant; sedative |
| cilostamide cilostamide: selective inhibitor of cyclic AMP phosphodiesterase & platelet aggregation; structure | 2.44 | 2 | 0 | quinolines | |
| cilostazol [no description available] | 2.44 | 2 | 0 | lactam; tetrazoles | anticoagulant; bronchodilator agent; EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor; fibrin modulating drug; neuroprotective agent; platelet aggregation inhibitor; vasodilator agent |
| cimetidine Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.. cimetidine : A member of the class of guanidines that consists of guanidine carrying a methyl substituent at position 1, a cyano group at position 2 and a 2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl group at position 3. It is a H2-receptor antagonist that inhibits the production of acid in stomach. | 2.44 | 2 | 0 | aliphatic sulfide; guanidines; imidazoles; nitrile | adjuvant; analgesic; anti-ulcer drug; H2-receptor antagonist; P450 inhibitor |
| cinoxacin Cinoxacin: Synthetic antimicrobial related to OXOLINIC ACID and NALIDIXIC ACID and used in URINARY TRACT INFECTIONS.. cinoxacin : A member of the class of cinnolines that is 6,7-methylenedioxycinnolin-4(1H)-one bearing an ethyl group at position 1 and a carboxylic acid group at position 3. An analogue of oxolinic acid, it has similar antibacterial actions. It was formerly used for the treatment of urinary tract infections. | 2.44 | 2 | 0 | cinnolines; oxacycle; oxo carboxylic acid | antibacterial drug; antiinfective agent |
| ciprofibrate [no description available] | 2.03 | 1 | 0 | cyclopropanes; monocarboxylic acid; organochlorine compound | antilipemic drug |
| clenbuterol Clenbuterol: A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma.. clenbuterol : A substituted aniline that is 2,6-dichloroaniline in which the hydrogen at position 4 has been replaced by a 2-(tert-butylamino)-1-hydroxyethyl group. | 2.08 | 1 | 0 | amino alcohol; dichlorobenzene; ethanolamines; primary arylamine; secondary amino compound; substituted aniline | beta-adrenergic agonist; bronchodilator agent; sympathomimetic agent |
| clofibrate angiokapsul: contains clofibrate & insoitolnicotinate | 2.03 | 1 | 0 | aromatic ether; ethyl ester; monochlorobenzenes | anticholesteremic drug; antilipemic drug; geroprotector; PPARalpha agonist |
| clotrimazole [no description available] | 2.44 | 2 | 0 | conazole antifungal drug; imidazole antifungal drug; imidazoles; monochlorobenzenes | antiinfective agent; environmental contaminant; xenobiotic |
| cx546 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine: structure in first source | 2.03 | 1 | 0 | ||
| cyclothiazide cyclothiazide: inhibits the desensitization of AMPA-type receptors; structure. cyclothiazide : 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted at positions 3, 5 and 6 by a 2-norbornen-5-yl group, chlorine, and a sulfonamide group, respectively. A thiazide diuretic, it has been used in the management of hypertension and oedema. | 2.03 | 1 | 0 | benzothiadiazine | antihypertensive agent; diuretic |
| dephostatin dephostatin: from Streptomyces sp. MJ742-NF5; structure given in first source | 2.03 | 1 | 0 | ||
| nonivamide nonivamide: has effect on sensory neurons. nonivamide : A capsaicinoid that is the carboxamide resulting from the formal condensation of the amino group of 4-hydroxy-3-methoxybenzylamine with the carboxy group of nonanoic acid. It is the active ingredient in many pepper sprays. | 2.03 | 1 | 0 | capsaicinoid; phenols | lachrymator |
| r 59022 R 59022: diacylglycerol kinase inhibitor; structure given in first source; platelet activator factor antagonist | 2.03 | 1 | 0 | diarylmethane | |
| diazoxide Diazoxide: A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.. diazoxide : A benzothiadiazine that is the S,S-dioxide of 2H-1,2,4-benzothiadiazine which is substituted at position 3 by a methyl group and at position 7 by chlorine. A peripheral vasodilator, it increases the concentration of glucose in the plasma and inhibits the secretion of insulin by the beta- cells of the pancreas. It is used orally in the management of intractable hypoglycaemia and intravenously in the management of hypertensive emergencies. | 2.03 | 1 | 0 | benzothiadiazine; organochlorine compound; sulfone | antihypertensive agent; beta-adrenergic agonist; bronchodilator agent; cardiotonic drug; diuretic; K-ATP channel agonist; sodium channel blocker; sympathomimetic agent; vasodilator agent |
| pentetic acid Pentetic Acid: An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium. | 2.03 | 1 | 0 | pentacarboxylic acid | copper chelator |
| diphenyleneiodonium diphenyleneiodonium: structure in first source; NADPH oxidase inhibitor. dibenziodolium : An organic cation that is fluorene in which the methylene group is replaced by a positively charged iodine. | 2.03 | 1 | 0 | organic cation | |
| dipyridamole Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752). dipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots. | 2.44 | 2 | 0 | piperidines; pyrimidopyrimidine; tertiary amino compound; tetrol | adenosine phosphodiesterase inhibitor; EC 3.5.4.4 (adenosine deaminase) inhibitor; platelet aggregation inhibitor; vasodilator agent |
| disopyramide Disopyramide: A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.. disopyramide : A monocarboxylic acid amide that is butanamide substituted by a diisopropylamino group at position 4, a phenyl group at position 2 and a pyridin-2-yl group at position 2. It is used as a anti-arrhythmia drug. | 2.03 | 1 | 0 | monocarboxylic acid amide; pyridines; tertiary amino compound | anti-arrhythmia drug |
| disulfiram [no description available] | 2.44 | 2 | 0 | organic disulfide; organosulfur acaricide | angiogenesis inhibitor; antineoplastic agent; apoptosis inducer; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; EC 3.1.1.1 (carboxylesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; ferroptosis inducer; fungicide; NF-kappaB inhibitor |
| 2-amino-7-phosphonoheptanoic acid 2-amino-7-phosphonoheptanoic acid: (D)-isomer active as an antagonist of N-methyl-D-aspartate excitation of central neurons; (L)-isomer inactive; RN given refers to cpd without isomeric designation | 2.03 | 1 | 0 | ||
| thiorphan Thiorphan: A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms. | 2.03 | 1 | 0 | N-acyl-amino acid | |
| 2,3-dimethoxy-1,4-naphthoquinone 2,3-dimethoxynaphthalene-1,4-dione : A naphthoquinone that is 1,4-naphthoquinone bearing two methoxy substituents at positions 2 and 3. Redox-cycling agent that induces intracellular superoxide anion formation and, depending on the concentration, induces cell proliferation, apoptosis or necrosis. Used to study the role of ROS in cell toxicity, apoptosis, and necrosis. | 2.44 | 2 | 0 | 1,4-naphthoquinones | |
| domperidone Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.. domperidone : 1-[3-(Piperidin-1-yl)propyl]-1,3-dihydro-2H-benzimidazol-2-one in which the 4-position of the piperidine ring is substituted by a 5-chloro-1,3-dihydro-2H-benzimidazol-2-on-1-yl group. A dopamine antagonist, it is used as an antiemetic for the short-term treatment of nausea and vomiting, and to control gastrointestinal effects of dopaminergic drugs given in the management of parkinsonism. The free base is used in oral suspensions, while the maleate salt is used in tablet preparations. | 2.44 | 2 | 0 | benzimidazoles; heteroarylpiperidine | antiemetic; dopaminergic antagonist |
| droperidol Droperidol: A butyrophenone with general properties similar to those of HALOPERIDOL. It is used in conjunction with an opioid analgesic such as FENTANYL to maintain the patient in a calm state of neuroleptanalgesia with indifference to surroundings but still able to cooperate with the surgeon. It is also used as a premedicant, as an antiemetic, and for the control of agitation in acute psychoses. (From Martindale, The Extra Pharmacopoeia, 29th ed, p593). droperidol : An organofluorine compound that is haloperidol in which the hydroxy group has been eliminated with the introduction of a double bond in the piperidine ring, and the 4-chlorophenyl group has been replaced by a benzimidazol-2-on-1-yl group. It is used in the management of chemotherapy-induced nausea and vomiting, and in conjunction with an opioid analgesic such as fentanyl to maintain the patient in a calm state of neuroleptanalgesia with indifference to surroundings but still able to cooperate with the surgeon. | 2.44 | 2 | 0 | aromatic ketone; benzimidazoles; organofluorine compound | anaesthesia adjuvant; antiemetic; dopaminergic antagonist; first generation antipsychotic |
| ebselen ebselen : A benzoselenazole that is 1,2-benzoselenazol-3-one carrying an additional phenyl substituent at position 2. Acts as a mimic of glutathione peroxidase. | 2.44 | 2 | 0 | benzoselenazole | anti-inflammatory drug; antibacterial agent; anticoronaviral agent; antifungal agent; antineoplastic agent; antioxidant; apoptosis inducer; EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor; EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor; EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor; EC 2.5.1.7 (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) inhibitor; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; EC 3.1.3.25 (inositol-phosphate phosphatase) inhibitor; EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor; EC 3.5.4.1 (cytosine deaminase) inhibitor; EC 5.1.3.2 (UDP-glucose 4-epimerase) inhibitor; enzyme mimic; ferroptosis inhibitor; genotoxin; hepatoprotective agent; neuroprotective agent; radical scavenger |
| ellipticine ellipticine : A organic heterotetracyclic compound that is pyrido[4,3-b]carbazole carrying two methyl substituents at positions 5 and 11. | 2.44 | 2 | 0 | indole alkaloid; organic heterotetracyclic compound; organonitrogen heterocyclic compound; polycyclic heteroarene | antineoplastic agent; plant metabolite |
| emodin Emodin: Purgative anthraquinone found in several plants, especially RHAMNUS PURSHIANA. It was formerly used as a laxative, but is now used mainly as a tool in toxicity studies.. emodin : A trihydroxyanthraquinone that is 9,10-anthraquinone which is substituted by hydroxy groups at positions 1, 3, and 8 and by a methyl group at position 6. It is present in the roots and barks of numerous plants (particularly rhubarb and buckthorn), moulds, and lichens. It is an active ingredient of various Chinese herbs. | 2.44 | 2 | 0 | trihydroxyanthraquinone | antineoplastic agent; laxative; plant metabolite; tyrosine kinase inhibitor |
| ethosuximide Ethosuximide: An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures.. ethosuximide : A dicarboximide that is pyrrolidine-2,5-dione in which the hydrogens at position 3 are substituted by one methyl and one ethyl group. An antiepileptic, it is used in the treatment of absence seizures and may be used for myoclonic seizures, but is ineffective against tonic-clonic seizures. | 2.03 | 1 | 0 | dicarboximide; pyrrolidinone | anticonvulsant; geroprotector; T-type calcium channel blocker |
| etodolac Etodolac: A non-steroidal anti-inflammatory agent and cyclooxygenase-2 (COX-2) inhibitor with potent analgesic and anti-arthritic properties. It has been shown to be effective in the treatment of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; and in the alleviation of postoperative pain (PAIN, POSTOPERATIVE).. etodolac : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is substituted by a 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl moiety. A preferential inhibitor of cyclo-oxygenase 2 and non-steroidal anti-inflammatory, it is used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. Administered as the racemate, only the (S)-enantiomer is active. | 2.03 | 1 | 0 | monocarboxylic acid; organic heterotricyclic compound | antipyretic; cyclooxygenase 2 inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| felbamate Felbamate: A PEGylated phenylcarbamate derivative that acts as an antagonist of NMDA RECEPTORS. It is used as an anticonvulsant, primarily for the treatment of SEIZURES in severe refractory EPILEPSY.. felbamate : The bis(carbamate ester) of 2-phenylpropane-1,3-diol. An anticonvulsant, it is used in the treatment of epilepsy. | 2.03 | 1 | 0 | carbamate ester | anticonvulsant; neuroprotective agent |
| felodipine Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.. felodipine : The mixed (methyl, ethyl) diester of 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid. A calcium-channel blocker, it lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. It is used in the management of hypertension and angina pectoris. | 2.44 | 2 | 0 | dichlorobenzene; dihydropyridine; ethyl ester; methyl ester | anti-arrhythmia drug; antihypertensive agent; calcium channel blocker; vasodilator agent |
| fenofibrate Pharmavit: a polyvitamin product, comprising vitamins A, D2, B1, B2, B6, C, E, nicotinamide, & calcium pantothene; may be a promising agent for application to human populations exposed to carcinogenic and genetic hazards of ionizing radiation; RN from CHEMLINE | 2.44 | 2 | 0 | aromatic ether; chlorobenzophenone; isopropyl ester; monochlorobenzenes | antilipemic drug; environmental contaminant; geroprotector; xenobiotic |
| berotek Fenoterol: A synthetic adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic.. fenoterol : A member of the class resorcinols that is 5-(1-hydroxyethyl)benzene-1,3-diol in which one of the methyl hydrogens is replaced by a 1-(4-hydroxyphenyl)propan-2-amino group. A beta2-adrenergic agonist, it is used (as the hydrobromide salt) as a bronchodilator in the management of reversible airway obstruction. | 2.08 | 1 | 0 | resorcinols; secondary alcohol; secondary amino compound | beta-adrenergic agonist; bronchodilator agent; sympathomimetic agent; tocolytic agent |
| flumazenil Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.. flumazenil : An organic heterotricyclic compound that is 5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted at positions 3, 5, 6, and 8 by ethoxycarbonyl, methyl, oxo, and fluoro groups, respectively. It is used as an antidote to benzodiazepine overdose. | 2.03 | 1 | 0 | ethyl ester; imidazobenzodiazepine; organofluorine compound | antidote to benzodiazepine poisoning; GABA antagonist |
| fluorouracil Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth. | 2.44 | 2 | 0 | nucleobase analogue; organofluorine compound | antimetabolite; antineoplastic agent; environmental contaminant; immunosuppressive agent; radiosensitizing agent; xenobiotic |
| fluspirilene Fluspirilene: A long-acting injectable antipsychotic agent used for chronic schizophrenia. | 2.44 | 2 | 0 | diarylmethane | |
| flutamide Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. | 2.44 | 2 | 0 | (trifluoromethyl)benzenes; monocarboxylic acid amide | androgen antagonist; antineoplastic agent |
| fpl 64176 FPL 64176: an activator of L-type calcium channels; structure given in first source. FPL 64176 : 1H-Pyrrole substituted at C-2 and -5 by methyl groups, at C-3 by methoxycarbonyl and at C-4 by a 2-benzylbenzoyl group. | 2.44 | 2 | 0 | carboxylic ester; pyrroles | calcium channel agonist |
| furafylline [no description available] | 2.03 | 1 | 0 | oxopurine | |
| furosemide Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.. furosemide : A chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2-ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure. | 2.44 | 2 | 0 | chlorobenzoic acid; furans; sulfonamide | environmental contaminant; loop diuretic; xenobiotic |
| fusaric acid Fusaric Acid: A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis. | 2.03 | 1 | 0 | aromatic carboxylic acid; pyridines | |
| gabapentin Gabapentin: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. gabapentin : A gamma-amino acid that is cyclohexane substituted at position 1 by aminomethyl and carboxymethyl groups. Used for treatment of neuropathic pain and restless legs syndrome. | 2.03 | 1 | 0 | gamma-amino acid | anticonvulsant; calcium channel blocker; environmental contaminant; xenobiotic |
| 4-amino-5-hexynoic acid 4-amino-5-hexynoic acid: structure | 2.03 | 1 | 0 | ||
| glipizide Glipizide: An oral hypoglycemic agent which is rapidly absorbed and completely metabolized.. glipizide : An N-sulfonylurea that is glyburide in which the (5-chloro-2-methoxybenzoyl group is replaced by a (5-methylpyrazin-2-yl)carbonyl group. An oral hypoglycemic agent, it is used in the treatment of type 2 diabetes mellitus. | 2.03 | 1 | 0 | aromatic amide; monocarboxylic acid amide; N-sulfonylurea; pyrazines | EC 2.7.1.33 (pantothenate kinase) inhibitor; hypoglycemic agent; insulin secretagogue |
| glyburide Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide. glyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group. | 2.44 | 2 | 0 | monochlorobenzenes; N-sulfonylurea | anti-arrhythmia drug; EC 2.7.1.33 (pantothenate kinase) inhibitor; EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor; hypoglycemic agent |
| 1-(5-isoquinolinesulfonyl)piperazine [no description available] | 2.03 | 1 | 0 | isoquinolines | |
| haloperidol Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279). haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. | 2.44 | 2 | 0 | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| hemicholinium 3 [no description available] | 2.03 | 1 | 0 | morpholines | |
| 4-fluorohexahydrosiladifenidol [no description available] | 2.03 | 1 | 0 | ||
| hydrochlorothiazide Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.. hydrochlorothiazide : A benzothiadiazine that is 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide substituted by a chloro group at position 6 and a sulfonamide at 7. It is diuretic used for the treatment of hypertension and congestive heart failure. | 2.03 | 1 | 0 | benzothiadiazine; organochlorine compound; sulfonamide | antihypertensive agent; diuretic; environmental contaminant; xenobiotic |
| hydroxyurea [no description available] | 2.03 | 1 | 0 | one-carbon compound; ureas | antimetabolite; antimitotic; antineoplastic agent; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; genotoxin; immunomodulator; radical scavenger; teratogenic agent |
| ibudilast [no description available] | 2.03 | 1 | 0 | pyrazolopyridine | |
| ibuprofen Midol: combination of cinnamedrine, phenacetin, aspirin & caffeine | 2.03 | 1 | 0 | monocarboxylic acid | antipyretic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; drug allergen; environmental contaminant; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug; radical scavenger; xenobiotic |
| ic 261 [no description available] | 2.44 | 2 | 0 | indoles | |
| ifenprodil ifenprodil: NMDA receptor antagonist | 2.03 | 1 | 0 | piperidines | |
| indirubin-3'-monoxime indirubin-3'-monoxime: has antiangiogenic activity. indirubin-3'-monoxime : A member of the class of biindoles that is indirubin in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime. | 2.44 | 2 | 0 | ||
| indomethacin Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.. indometacin : A member of the class of indole-3-acetic acids that is indole-3-acetic acid in which the indole ring is substituted at positions 1, 2 and 5 by p-chlorobenzoyl, methyl, and methoxy groups, respectively. A non-steroidal anti-inflammatory drug, it is used in the treatment of musculoskeletal and joint disorders including osteoarthritis, rheumatoid arthritis, gout, bursitis and tendinitis. | 2.03 | 1 | 0 | aromatic ether; indole-3-acetic acids; monochlorobenzenes; N-acylindole | analgesic; drug metabolite; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; gout suppressant; non-steroidal anti-inflammatory drug; xenobiotic metabolite; xenobiotic |
| iodoacetamide [no description available] | 2.03 | 1 | 0 | ||
| 1-methyl-3-isobutylxanthine 1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES. 3-isobutyl-1-methylxanthine : An oxopurine that is xanthine which is substituted at positions 1 and 3 by methyl and isobutyl groups, respectively. | 2.03 | 1 | 0 | 3-isobutyl-1-methylxanthine | |
| isoetharine Isoetharine: Adrenergic beta-2 agonist used as bronchodilator for emphysema, bronchitis and asthma. | 2.08 | 1 | 0 | catecholamine | |
| 4-piperidinecarboxylic acid 4-piperidinecarboxylic acid: structure in first source | 2.44 | 2 | 0 | ||
| isoproterenol Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.. isoprenaline : A secondary amino compound that is noradrenaline in which one of the hydrogens attached to the nitrogen is replaced by an isopropyl group. A sympathomimetic acting almost exclusively on beta-adrenergic receptors, it is used (mainly as the hydrochloride salt) as a bronghodilator and heart stimulant for the management of a variety of cardiac disorders. | 3.17 | 5 | 0 | catechols; secondary alcohol; secondary amino compound | beta-adrenergic agonist; bronchodilator agent; cardiotonic drug; sympathomimetic agent |
| 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline WHI P131: a quinazoline derivative, inhibitor of glioblastoma cell adhesion and migration | 2.03 | 1 | 0 | ||
| jl 18 JL 18: a pyridobenzodiazepine derivative bioisoster of clozapine | 2.44 | 2 | 0 | ||
| nsc 664704 kenpaullone: inhibits CDK1/cyclin B; structure in first source. kenpaullone : An indolobenzazepine that is paullone in which the hydrogen at position 9 is replaced by a bromo substituent. It is an ATP-competitive inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3beta (GSK3beta). | 2.44 | 2 | 0 | indolobenzazepine; lactam; organobromine compound | cardioprotective agent; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor; EC 2.7.11.26 (tau-protein kinase) inhibitor; geroprotector |
| ketoconazole 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively. | 2.44 | 2 | 0 | dichlorobenzene; dioxolane; ether; imidazoles; N-acylpiperazine; N-arylpiperazine | |
| ketoprofen Ketoprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.. ketoprofen : An oxo monocarboxylic acid that consists of propionic acid substituted by a 3-benzoylphenyl group at position 2. | 2.03 | 1 | 0 | benzophenones; oxo monocarboxylic acid | antipyretic; drug allergen; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; non-steroidal anti-inflammatory drug; xenobiotic |
| kynurenic acid Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool.. kynurenic acid : A quinolinemonocarboxylic acid that is quinoline-2-carboxylic acid substituted by a hydroxy group at C-4. | 2.03 | 1 | 0 | monohydroxyquinoline; quinolinemonocarboxylic acid | G-protein-coupled receptor agonist; human metabolite; neuroprotective agent; nicotinic antagonist; NMDA receptor antagonist; Saccharomyces cerevisiae metabolite |
| 2-amino-3-phosphonopropionic acid 2-amino-3-phosphonopropionic acid: metabotropic glutamate receptor antagonist; do not confuse AP-3 used as an abbreviation for this with enhancer-binding protein AP-3 (a trans-activator) or clathrin assembly protein AP-3. 2-amino-3-phosphonopropanoic acid : A non-proteinogenc alpha-amino acid that is alanine in which one of the hydrogens of the terminal methyl group has been replaced by a dihydroxy(oxido)-lambda(5)-phosphanyl group. | 2.03 | 1 | 0 | alanine derivative; non-proteinogenic alpha-amino acid; phosphonic acids | human metabolite; metabotropic glutamate receptor antagonist |
| lamotrigine [no description available] | 2.03 | 1 | 0 | 1,2,4-triazines; dichlorobenzene; primary arylamine | anticonvulsant; antidepressant; antimanic drug; calcium channel blocker; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; excitatory amino acid antagonist; geroprotector; non-narcotic analgesic; xenobiotic |
| lansoprazole Lansoprazole: A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers. | 2.44 | 2 | 0 | benzimidazoles; pyridines; sulfoxide | anti-ulcer drug; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor |
| beta-lapachone beta-lapachone: antineoplastic inhibitor of reverse transcriptase, DNA topoisomerase, and DNA polymerase. beta-lapachone : A benzochromenone that is 3,4-dihydro-2H-benzo[h]chromene-5,6-dione substituted by geminal methyl groups at position 2. Isolated from Tabebuia avellanedae, it exhibits antineoplastic and anti-inflammatory activities. | 2.44 | 2 | 0 | benzochromenone; orthoquinones | anti-inflammatory agent; antineoplastic agent; plant metabolite |
| leflunomide Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.. leflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide. | 2.03 | 1 | 0 | (trifluoromethyl)benzenes; isoxazoles; monocarboxylic acid amide | antineoplastic agent; antiparasitic agent; EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; hepatotoxic agent; immunosuppressive agent; non-steroidal anti-inflammatory drug; prodrug; pyrimidine synthesis inhibitor; tyrosine kinase inhibitor |
| linopirdine linopirdine: acetylcholine releasing drug | 2.44 | 2 | 0 | indoles | |
| loratadine Loratadine: A second-generation histamine H1 receptor antagonist used in the treatment of allergic rhinitis and urticaria. Unlike most classical antihistamines (HISTAMINE H1 ANTAGONISTS) it lacks central nervous system depressing effects such as drowsiness.. loratadine : A benzocycloheptapyridine that is 6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine substituted by a chloro group at position 8 and a 1-(ethoxycarbonyl)piperidin-4-ylidene group at position 11. It is a H1-receptor antagonist commonly employed in the treatment of allergic disorders. | 2.44 | 2 | 0 | benzocycloheptapyridine; ethyl ester; N-acylpiperidine; organochlorine compound; tertiary carboxamide | anti-allergic agent; cholinergic antagonist; geroprotector; H1-receptor antagonist |
| loxoprofen loxoprofen: RN given refers to parent cpd without isomeric designation; structure in first source. loxoprofen : A monocarboxylic acid that is propionic acid in which one of the hydrogens at position 2 is substituted by a 4-[(2-oxocyclopentyl)methyl]phenyl group. A prodrug that is rapidly converted into its active trans-alcohol metabolite following oral administration. | 2.03 | 1 | 0 | cyclopentanones; monocarboxylic acid | antipyretic; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug; prodrug |
| 2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source | 2.03 | 1 | 0 | chromones; morpholines; organochlorine compound | autophagy inhibitor; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; geroprotector |
| meclofenamate sodium anhydrous [no description available] | 2.03 | 1 | 0 | organic sodium salt | |
| metaproterenol Metaproterenol: A beta-2 adrenergic agonist used in the treatment of ASTHMA and BRONCHIAL SPASM.. orciprenaline : A racemate composed of equimolar amounts of (R)- and (S)-orciprenaline. Used (as its sulfate salt) to relax the airway muscles and improve breathing for patients suffering from asthma or bronchitis.. 5-[1-hydroxy-2-(isopropanylamino)ethyl]benzene-1,3-diol : A member of the class of resorcinols bearing an additional 1-hydroxy-2-(isopropanylamino)ethyl substituent at position 5 of resorcinol itself. | 2.08 | 1 | 0 | aralkylamino compound; phenylethanolamines; resorcinols; secondary alcohol; secondary amino compound | |
| methiothepin Methiothepin: A serotonin receptor antagonist in the CENTRAL NERVOUS SYSTEM used as an antipsychotic.. methiothepin : A dibenzothiepine that is 10,11-dihydrodibenzo[b,f]thiepine bearing additional methylthio and 4-methylpiperazin-1-yl substituents at positions 8 and 10 respectively. Potent 5-HT2 antagonist, also active as 5-HT1 antagonist. Differentiates 5-HT1D sub-types. Also displays affinity for rodent 5-HT5B, 5-HT5A, 5-HT7 and 5-HT6 receptors (pK1 values are 6.6, 7.0, 8.4 and 8.7 respectively). | 2.03 | 1 | 0 | aryl sulfide; dibenzothiepine; N-alkylpiperazine; tertiary amino compound | antipsychotic agent; dopaminergic antagonist; geroprotector; serotonergic antagonist |
| methoctramine [no description available] | 2.03 | 1 | 0 | aromatic ether; tetramine | muscarinic antagonist |
| nocodazole [no description available] | 2.44 | 2 | 0 | aromatic ketone; benzimidazoles; carbamate ester; thiophenes | antimitotic; antineoplastic agent; microtubule-destabilising agent; tubulin modulator |
| 3-Hydroxy-alpha-methyl-DL-tyrosine [no description available] | 2.03 | 1 | 0 | benzenes; monocarboxylic acid | |
| metolazone Metolazone: A quinazoline-sulfonamide derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS.. metolazone : A quinazoline that consists of 1,2,3,4-tetrahydroquinazolin-4-one bearing additional methyl, 2-tolyl, sulfamyl and chloro substituents at positions 2, 3, 6 and 7 respectively. A quinazoline diuretic, with properties similar to thiazide diuretics. | 2.44 | 2 | 0 | organochlorine compound; quinazolines; sulfonamide | antihypertensive agent; diuretic; ion transport inhibitor |
| milrinone [no description available] | 2.03 | 1 | 0 | bipyridines; nitrile; pyridone | cardiotonic drug; EC 3.1.4.17 (3',5'-cyclic-nucleotide phosphodiesterase) inhibitor; platelet aggregation inhibitor; vasodilator agent |
| minoxidil Minoxidil: A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371). minoxidil : A pyrimidine N-oxide that is pyrimidine-2,4-diamine 3-oxide substituted by a piperidin-1-yl group at position 6. | 2.03 | 1 | 0 | dialkylarylamine; tertiary amino compound | |
| mitotane Mitotane: A derivative of the insecticide DICHLORODIPHENYLDICHLOROETHANE that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression. | 2.03 | 1 | 0 | diarylmethane | |
| mitoxantrone Mitoxantrone: An anthracenedione-derived antineoplastic agent.. mitoxantrone : A dihydroxyanthraquinone that is 1,4-dihydroxy-9,10-anthraquinone which is substituted by 6-hydroxy-1,4-diazahexyl groups at positions 5 and 8. | 2.44 | 2 | 0 | dihydroxyanthraquinone | analgesic; antineoplastic agent |
| ml 7 ML-7 : An N-sulfonyldiazepane resullting from the formal condensation of 5-iodo-1-naphthylsulfonic acid with one of the nitrogens of 1,4-diazepane. It is a selective inhibitor of myosin light chain kinase (EC 2.7.11.18). | 2.44 | 2 | 0 | N-sulfonyldiazepane; organoiodine compound | EC 2.7.11.18 (myosin-light-chain kinase) inhibitor |
| ml 9 [no description available] | 2.05 | 1 | 0 | naphthalenes; sulfonic acid derivative | |
| n-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide: calmodulin antagonist; structure given in first source. N-(4-aminobutyl)-5-chloronaphthalene-2-sulfonamide : A sulfonamide that is 5-chloronaphthalene-2-sulfonamide in which one of the hydrogens of the nitrogen atom is substituted by a 4-aminobutyl group. | 2.03 | 1 | 0 | naphthalenes; organochlorine compound; primary amino compound; sulfonamide | |
| n-bromoacetamide [no description available] | 2.03 | 1 | 0 | ||
| ethylmaleimide Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies. | 2.03 | 1 | 0 | maleimides | anticoronaviral agent; EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor; EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor; EC 2.7.1.1 (hexokinase) inhibitor |
| fg 7142 FG 7142: benzodiazepine receptor agonist | 2.44 | 2 | 0 | beta-carbolines | |
| fenamic acid fenamic acid: has chloride and potassium channel-blocking activity; RN given refers to parent cpd. fenamic acid : An aminobenzoic acid that is the N-phenyl derivative of anthranilic acid. It acts as a parent skeleton for the synthesis of several non-steroidal anti-inflammatory drugs. | 2.03 | 1 | 0 | aminobenzoic acid; secondary amino compound | membrane transport modulator |
| n 0840 N(6)-cyclopentyl-9-methyladenine: selective, orally active A(1) adenosine receptor antagonist | 2.44 | 2 | 0 | ||
| nialamide Nialamide: An MAO inhibitor that is used as an antidepressive agent. | 2.44 | 2 | 0 | organonitrogen compound; organooxygen compound | |
| niclosamide Niclosamide: An antihelmintic that is active against most tapeworms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p48). niclosamide : A secondary carboxamide resulting from the formal condensation of the carboxy group of 5-chlorosalicylic acid with the amino group of 2-chloro-4-nitroaniline. It is an oral anthelmintic drug approved for use against tapeworm infections. | 2.44 | 2 | 0 | benzamides; C-nitro compound; monochlorobenzenes; salicylanilides; secondary carboxamide | anthelminthic drug; anticoronaviral agent; antiparasitic agent; apoptosis inducer; molluscicide; piscicide; STAT3 inhibitor |
| nifedipine Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. | 2.44 | 2 | 0 | C-nitro compound; dihydropyridine; methyl ester | calcium channel blocker; human metabolite; tocolytic agent; vasodilator agent |
| niflumic acid Niflumic Acid: An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis. | 2.03 | 1 | 0 | aromatic carboxylic acid; pyridines | |
| nilutamide [no description available] | 2.03 | 1 | 0 | (trifluoromethyl)benzenes; C-nitro compound; imidazolidinone | androgen antagonist; antineoplastic agent |
| nimesulide nimesulide: structure. nimesulide : An aromatic ether having phenyl and 2-methylsulfonamido-5-nitrophenyl as the two aryl groups. | 2.03 | 1 | 0 | aromatic ether; C-nitro compound; sulfonamide | cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug |
| nimodipine Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.. nimodipine : A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a (2-methoxyethoxy)carbonyl group at position 3, a m-nitrophenyl group at position 4, and an isopropoxycarbonyl group at position 5. An L-type calcium channel blocker, it acts particularly on cerebral circulation, and is used both orally and intravenously for the prevention and treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm. | 2.44 | 2 | 0 | 2-methoxyethyl ester; C-nitro compound; dicarboxylic acids and O-substituted derivatives; diester; dihydropyridine; isopropyl ester | antihypertensive agent; calcium channel blocker; cardiovascular drug; vasodilator agent |
| nipecotic acid nipecotic acid: RN given refers to cpd without isomeric designation. nipecotic acid : A piperidinemonocarboxylic acid that is piperidine in which one of the hydrogens at position 3 is substituted by a carboxylic acid group. | 2.03 | 1 | 0 | beta-amino acid; piperidinemonocarboxylic acid | |
| nisoxetine nisoxetine: potent inhibitor for norepinephrine uptake into rat brain synaptosomes & brain; NM refers to (+-)-isomer; RN given refers to parent cpd; structure. nisoxetine : A secondary amino compound that is N-methyl-3-phenylpropan-1-amine substituted at position 3 by a 2-methoxyphenoxy group. | 2.08 | 1 | 0 | aromatic ether; secondary amino compound | adrenergic uptake inhibitor; antidepressant |
| nitrendipine Nitrendipine: A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.. nitrendipine : A dihydropyridine that is 1,4-dihydropyridine substituted by methyl groups at positions 2 and 6, a 3-nitrophenyl group at position 4, a ethoxycarbonyl group at position 3 and a methoxycarbonyl group at position 5. It is a calcium-channel blocker used in the treatment of hypertension. | 2.44 | 2 | 0 | C-nitro compound; dicarboxylic acids and O-substituted derivatives; diester; dihydropyridine; ethyl ester; methyl ester | antihypertensive agent; calcium channel blocker; geroprotector; vasodilator agent |
| masoprocol nordihydroguaretic acid: antioxidant compound found in the creosote bush (Larrea tridentata) | 2.44 | 2 | 0 | catechols; lignan; tetrol | antioxidant; ferroptosis inhibitor; geroprotector; plant metabolite |
| 5-nitro-2-(3-phenylpropylamino)benzoic acid 5-nitro-2-(3-phenylpropylamino)benzoic acid: structure given in first source; chloride channel antagonist | 2.44 | 2 | 0 | nitrobenzoic acid | |
| ns 2028 NS 2028: structure in first source | 2.03 | 1 | 0 | ||
| ns 1619 NS 1619: structure given in first source. NS 1619 : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which the hydrogens at positions 1 and 5 are replaced are replaced by 2-hydroxy-5-(trifluoromethyl)phenyl and trifluoromethyl groups, respectively. It is an opener/activator of the large-conductance calcium-activated potassium channel (Bkca). | 2.44 | 2 | 0 | (trifluoromethyl)benzenes; benzimidazoles; phenols | potassium channel opener |
| o(6)-benzylguanine O(6)-benzylguanine: a suicide inhibitor of O(6)-methylguanine-DNA methyltransferase activity | 2.03 | 1 | 0 | ||
| ofloxacin Ofloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.. 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid : An oxazinoquinoline that is 2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinolin-7-one substituted by methyl, carboxy, fluoro, and 4-methylpiperazin-1-yl groups at positions 3, 6, 9, and 10, respectively.. ofloxacin : A racemate comprising equimolar amounts of levofloxacin and dextrofloxacin. It is a synthetic fluoroquinolone antibacterial agent which inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. | 2.44 | 2 | 0 | 3-oxo monocarboxylic acid; N-arylpiperazine; N-methylpiperazine; organofluorine compound; oxazinoquinoline | |
| olomoucine olomoucine: inhibits protein P34CDC2. olomoucine : A 9H-purine that is substituted by a (2-hydroxyethyl)nitrilo, benzylnitrilo and a methyl group at positions 2,6 and 9, respectively. It is a cyclin-dependent kinase inhibitor. | 2.44 | 2 | 0 | 2,6-diaminopurines; ethanolamines | EC 2.7.11.22 (cyclin-dependent kinase) inhibitor |
| oxaprozin Oxaprozin: An oxazole-propionic acid derivative, cyclooxygenase inhibitor, and non-steroidal anti-inflammatory drug that is used in the treatment of pain and inflammation associated with of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; and ARTHRITIS, JUVENILE.. oxaprozin : A monocarboxylic acid that is a propionic acid derivative having a 4,5-diphenyl-1,3-oxazol-2-yl substituent at position 3. It is non-steroidal anti-inflammatory drug commonly used to relieve the pain and inflammatory responses associated with osteoarthritis and rheumatoid arthritis. | 2.44 | 2 | 0 | 1,3-oxazoles; monocarboxylic acid | analgesic; non-steroidal anti-inflammatory drug |
| oxatomide oxatomide: structure; an anti-allergic & an anti-asthmatic. oxatomide : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one substituted by a 3-[4-(diphenylmethyl)piperazin-1-yl]propyl group at position 1. It is an anti-allergic drug. | 2.44 | 2 | 0 | benzimidazoles; diarylmethane; N-alkylpiperazine | anti-allergic agent; anti-inflammatory agent; geroprotector; H1-receptor antagonist; serotonergic antagonist |
| oxiracetam oxiracetam: structure in first source | 2.03 | 1 | 0 | organonitrogen compound; organooxygen compound | |
| oxolinic acid quinolone antibiotic : An organonitrogen heterocyclic antibiotic whose structure contains a quinolone or quinolone-related skeleton. | 2.03 | 1 | 0 | aromatic carboxylic acid; organic heterotricyclic compound; oxacycle; quinolinemonocarboxylic acid; quinolone antibiotic | antibacterial drug; antifungal agent; antiinfective agent; antimicrobial agent; enzyme inhibitor |
| quinone benzoquinone : The simplest members of the class of benzoquinones, consisting of cyclohexadiene which is substituted by two oxo groups.. 1,4-benzoquinone : The simplest member of the class of 1,4-benzoquinones, obtained by the formal oxidation of hydroquinone to the corresponding diketone. It is a metabolite of benzene.. quinone : Compounds having a fully conjugated cyclic dione structure, such as that of benzoquinones, derived from aromatic compounds by conversion of an even number of -CH= groups into -C(=O)- groups with any necessary rearrangement of double bonds (polycyclic and heterocyclic analogues are included). | 2.03 | 1 | 0 | 1,4-benzoquinones | cofactor; human xenobiotic metabolite; mouse metabolite |
| fenclonine Fenclonine: A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin. | 2.03 | 1 | 0 | phenylalanine derivative | |
| palmidrol palmidrol: a cannabinoid receptor-inactive eCB-related molecule used as prophylactic in helping to prevent respiratory viral infection. palmitoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of palmitic (hexadecanoic) acid. | 2.44 | 2 | 0 | endocannabinoid; N-(long-chain-acyl)ethanolamine; N-(saturated fatty acyl)ethanolamine | anti-inflammatory drug; anticonvulsant; antihypertensive agent; neuroprotective agent |
| 1,7-dimethylxanthine 1,7-dimethylxanthine : A dimethylxanthine having the two methyl groups located at positions 1 and 7. It is a metabolite of caffeine and theobromine in animals. | 2.03 | 1 | 0 | dimethylxanthine | central nervous system stimulant; human blood serum metabolite; human xenobiotic metabolite; mouse metabolite |
| pd 169316 2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole: p38 MAP kinase inhibitor | 2.05 | 1 | 0 | imidazoles | |
| pd 98059 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one: inhibits MAP kinase kinase (MEK) activity, p42 MAPK and p44 MAPK; structure in first source. 2-(2-amino-3-methoxyphenyl)chromen-4-one : A member of the class of monomethoxyflavones that is 3'-methoxyflavone bearing an additional amino substituent at position 2'. | 2.44 | 2 | 0 | aromatic amine; monomethoxyflavone | EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor; geroprotector |
| pentamidine Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects.. pentamidine : A diether consisting of pentane-1,5-diol in which both hydroxyl hydrogens have been replaced by 4-amidinophenyl groups. A trypanocidal drug that is used for treatment of cutaneous leishmaniasis and Chagas disease. | 2.03 | 1 | 0 | aromatic ether; carboxamidine; diether | anti-inflammatory agent; antifungal agent; calmodulin antagonist; chemokine receptor 5 antagonist; EC 2.3.1.48 (histone acetyltransferase) inhibitor; NMDA receptor antagonist; S100 calcium-binding protein B inhibitor; trypanocidal drug; xenobiotic |
| pentoxifylline [no description available] | 2.03 | 1 | 0 | oxopurine | |
| perphenazine Perphenazine: An antipsychotic phenothiazine derivative with actions and uses similar to those of CHLORPROMAZINE.. perphenazine : A phenothiazine derivative in which the phenothiazine tricycle carries a chloro substituent at the 2-position and a 3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl group at N-10. | 2.44 | 2 | 0 | N-(2-hydroxyethyl)piperazine; N-alkylpiperazine; organochlorine compound; phenothiazines | antiemetic; dopaminergic antagonist; phenothiazine antipsychotic drug |
| phenyl biguanide phenyl biguanide: RN given refers to parent cpd. phenyl biguanide : A member of the class of biguanides that is biguanide in which one of the terminal nitrogen atoms is substituted by a phenyl group. | 2.44 | 2 | 0 | guanidines | central nervous system drug |
| phenylbutazone Phenylbutazone: A butyl-diphenyl-pyrazolidinedione that has anti-inflammatory, antipyretic, and analgesic activities. It has been used in ANKYLOSING SPONDYLITIS; RHEUMATOID ARTHRITIS; and REACTIVE ARTHRITIS.. phenylbutazone : A member of the class of pyrazolidines that is 1,2-diphenylpyrazolidine-3,5-dione carrying a butyl group at the 4-position. | 2.44 | 2 | 0 | pyrazolidines | antirheumatic drug; EC 1.1.1.184 [carbonyl reductase (NADPH)] inhibitor; metabolite; non-narcotic analgesic; non-steroidal anti-inflammatory drug; peripheral nervous system drug |
| phloretin [no description available] | 2.44 | 2 | 0 | dihydrochalcones | antineoplastic agent; plant metabolite |
| picotamide picotamide: has anticoagulant & fibrinolytic properties; structure | 2.44 | 2 | 0 | benzamides | |
| pinacidil Pinacidil: A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed) | 2.44 | 2 | 0 | pyridines | |
| pindolol Pindolol: A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638). pindolol : A member of the class of indols which is the 2-hydroxy-3-(isopropylamino)propyl ether derivative of 1H-indol-4-ol. | 2.03 | 1 | 0 | indoles; secondary amine | antiglaucoma drug; antihypertensive agent; beta-adrenergic antagonist; serotonergic antagonist; vasodilator agent |
| piperidine-4-sulfonic acid piperidine-4-sulfonic acid: specific GABA agonist | 2.03 | 1 | 0 | ||
| piracetam Piracetam: A compound suggested to be both a nootropic and a neuroprotective agent. | 2.03 | 1 | 0 | organonitrogen compound; organooxygen compound | |
| pirenperone [no description available] | 2.44 | 2 | 0 | aromatic ketone | |
| praziquantel azinox: Russian drug | 2.44 | 2 | 0 | isoquinolines | |
| primidone Primidone: A barbiturate derivative that acts as a GABA modulator and anti-epileptic agent. It is partly metabolized to PHENOBARBITAL in the body and owes some of its actions to this metabolite.. primidone : A pyrimidone that is dihydropyrimidine-4,6(1H,5H)-dione substituted by an ethyl and a phenyl group at position 5. It is used as an anticonvulsant for treatment of various types of seizures. | 2.03 | 1 | 0 | pyrimidone | anticonvulsant; environmental contaminant; xenobiotic |
| procaterol Procaterol: A long-acting beta-2-adrenergic receptor agonist. | 3.69 | 3 | 0 | quinolines | |
| proglumide Proglumide: A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers.. proglumide : A racemate composed of equal amounts of (R)- and (S)-proglumide. A non-selective CCK antagonist that was used primarily for treatment of stomach ulcers, but has been replaced by newer drugs.. N(2)-benzoyl-N,N-dipropyl-alpha-glutamine : A dicarboxylic acid monoamide obtained by formal condensation of the alpha-carboxy group of N-benzoylglutamic acid with dippropylamine. | 2.03 | 1 | 0 | benzamides; dicarboxylic acid monoamide; glutamine derivative; racemate | anti-ulcer drug; cholecystokinin antagonist; cholinergic antagonist; delta-opioid receptor agonist; drug metabolite; gastrointestinal drug; opioid analgesic; xenobiotic metabolite |
| propentofylline [no description available] | 2.44 | 2 | 0 | oxopurine | |
| propofol Propofol: An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.. propofol : A phenol resulting from the formal substitution of the hydrogen at the 2 position of 1,3-diisopropylbenzene by a hydroxy group. | 2.03 | 1 | 0 | phenols | anticonvulsant; antiemetic; intravenous anaesthetic; radical scavenger; sedative |
| pf 5901 alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol: structure given in first source; platelet activating factor antagonist | 2.44 | 2 | 0 | quinolines | |
| riluzole Riluzole: A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS. | 2.44 | 2 | 0 | benzothiazoles | |
| risperidone Risperidone: A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.. risperidone : A member of the class of pyridopyrimidines that is 2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one carrying an additional 2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl group at position 2. | 2.44 | 2 | 0 | 1,2-benzoxazoles; heteroarylpiperidine; organofluorine compound; pyridopyrimidine | alpha-adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; H1-receptor antagonist; psychotropic drug; second generation antipsychotic; serotonergic antagonist |
| ritanserin Ritanserin: A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure.. ritanserin : A thiazolopyrimidine that is 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one which is substituted at position 7 by a methyl group and at position 6 by a 2-{4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl}ethyl group. A potent and long-acting seratonin (5-hydroxytryptamine, 5-HT) antagonist of the subtype 5-HT2 (Ki = 0.39 nM), it is used in the treatment of a variety of disorders including anxiety, depression and schizophrenia. It has little sedative action. | 2.44 | 2 | 0 | organofluorine compound; piperidines; thiazolopyrimidine | antidepressant; antipsychotic agent; anxiolytic drug; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; serotonergic antagonist |
| 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone 4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases. | 2.03 | 1 | 0 | methoxybenzenes | |
| rolipram [no description available] | 2.03 | 1 | 0 | pyrrolidin-2-ones | antidepressant; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor |
| salmeterol xinafoate salmeterol : A racemate consisting of equal parts of (R)- and (S)-salmeterol. It is a potent and selective beta2-adrenoceptor agonist (EC50 = 5.3 nM). Unlike other beta2 agonists, it binds to the exo-site domain of beta2 receptors, producing a slow onset of action and prolonged activation.. 2-(hydroxymethyl)-4-(1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl)phenol : A phenol having a hydroxymethyl group at C-2 and a 1-hydroxy-2-{[6-(4-phenylbutoxy)hexyl]amino}ethyl group at C-4; derivative of phenylethanolamine. | 5.23 | 18 | 0 | ether; phenols; primary alcohol; secondary alcohol; secondary amino compound | |
| sb 202190 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole: structure given in first source; inhibits p38 MAP kinase | 2.44 | 2 | 0 | imidazoles; organofluorine compound; phenols; pyridines | apoptosis inducer; EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor |
| sobuzoxane sobuzoxane: used in treatment of leukemia L1210 | 2.03 | 1 | 0 | organic molecular entity | |
| spiroxatrine spiroxatrine: structure | 2.44 | 2 | 0 | imidazolidines | |
| sq 22536 9-(tetrahydrofuryl)adenine : A nucleoside analogue that is adenine in which the nitrogen at position 9 has been substituted by a tetrahydrofuran-2-yl group. It is an adenylate cyclase inhibitor. | 2.03 | 1 | 0 | nucleoside analogue; oxolanes | EC 4.6.1.1 (adenylate cyclase) inhibitor |
| sulfaphenazole Sulfaphenazole: A sulfonilamide anti-infective agent.. sulfaphenazole : A sulfonamide that is sulfanilamide in which the sulfonamide nitrogen is substituted by a 1-phenyl-1H-pyrazol-5-yl group. It is a selective inhibitor of cytochrome P450 (CYP) 2C9 isozyme, and antibacterial agent. | 2.03 | 1 | 0 | primary amino compound; pyrazoles; substituted aniline; sulfonamide antibiotic; sulfonamide | antibacterial drug; EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor; EC 1.14.13.67 (quinine 3-monooxygenase) inhibitor; P450 inhibitor |
| sulpiride Sulpiride: A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed). sulpiride : A member of the class of benzamides obtained from formal condensation between the carboxy group of 2-methoxy-5-sulfamoylbenzoic acid and the primary amino group of (1-ethylpyrrolidin-2-yl)methylamine. | 2.03 | 1 | 0 | benzamides; N-alkylpyrrolidine; sulfonamide | antidepressant; antiemetic; antipsychotic agent; dopaminergic antagonist |
| t0156 [no description available] | 2.44 | 2 | 0 | naphthyridine derivative | |
| 1,4-bis(2-(3,5-dichloropyridyloxy))benzene 1,4-bis(2-(3,5-dichloropyridyloxy))benzene: potent phenobarbital-like inducer of microsomal monooxygenase activity; structure given in first source | 2.03 | 1 | 0 | ||
| terbutaline Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.. terbutaline : A member of the class of phenylethanolamines that is catechol substituted at position 5 by a 2-(tert-butylamino)-1-hydroxyethyl group. | 2.48 | 2 | 0 | phenylethanolamines; resorcinols | anti-asthmatic drug; beta-adrenergic agonist; bronchodilator agent; EC 3.1.1.7 (acetylcholinesterase) inhibitor; hypoglycemic agent; sympathomimetic agent; tocolytic agent |
| terfenadine Terfenadine: A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME. | 2.44 | 2 | 0 | diarylmethane | |
| tetraisopropylpyrophosphamide Tetraisopropylpyrophosphamide: N,N',N'',N'''-Tetraisopropylpyrophosphamide. A specific inhibitor of pseudocholinesterases. It is commonly used experimentally to determine whether pseudo- or acetylcholinesterases are involved in an enzymatic process. | 2.44 | 2 | 0 | phosphoramide | |
| thalidomide Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group. | 2.03 | 1 | 0 | phthalimides; piperidones | |
| theobromine Theobromine: 3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than THEOPHYLLINE and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9). theobromine : A dimethylxanthine having the two methyl groups located at positions 3 and 7. A purine alkaloid derived from the cacao plant, it is found in chocolate, as well as in a number of other foods, and is a vasodilator, diuretic and heart stimulator. | 2.03 | 1 | 0 | dimethylxanthine | adenosine receptor antagonist; bronchodilator agent; food component; human blood serum metabolite; mouse metabolite; plant metabolite; vasodilator agent |
| 8-(n,n-diethylamino)octyl-3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate: intracellular calcium antagonist; RN given refers to parent cpd | 2.03 | 1 | 0 | trihydroxybenzoic acid | |
| tolazamide Tolazamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE.. tolazamide : An N-sulfonylurea that is 1-tosylurea in which a hydrogen attached to the nitrogen at position 3 is replaced by an azepan-1-yl group. A hypoglycemic agent, it is used for the treatment of type 2 diabetes mellitus. | 2.03 | 1 | 0 | N-sulfonylurea | hypoglycemic agent; potassium channel blocker |
| tolbutamide Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290). tolbutamide : An N-sulfonylurea that consists of 1-butylurea having a tosyl group attached at the 3-position. | 2.03 | 1 | 0 | N-sulfonylurea | human metabolite; hypoglycemic agent; insulin secretagogue; potassium channel blocker |
| (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid: a GABA-C receptor antagonist; structure in first source | 2.03 | 1 | 0 | ||
| ici 136,753 [no description available] | 2.44 | 2 | 0 | pyrazolopyridine | |
| triamterene Triamterene: A pteridinetriamine compound that inhibits SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS.. triamterene : Pteridine substituted at positions 2, 4 and 7 with amino groups and at position 6 with a phenyl group. A sodium channel blocker, it is used as a diuretic in the treatment of hypertension and oedema. | 2.44 | 2 | 0 | pteridines | diuretic; sodium channel blocker |
| trimethoprim Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.. trimethoprim : An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge. | 2.44 | 2 | 0 | aminopyrimidine; methoxybenzenes | antibacterial drug; diuretic; drug allergen; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; environmental contaminant; xenobiotic |
| tropicamide Tropicamide: One of the MUSCARINIC ANTAGONISTS with pharmacologic action similar to ATROPINE and used mainly as an ophthalmic parasympatholytic or mydriatic. | 2.03 | 1 | 0 | acetamides | |
| tyrphostin a9 [no description available] | 2.44 | 2 | 0 | alkylbenzene | geroprotector |
| vigabatrin [no description available] | 2.03 | 1 | 0 | gamma-amino acid | anticonvulsant; EC 2.6.1.19 (4-aminobutyrate--2-oxoglutarate transaminase) inhibitor |
| 8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine 8-(4-((2-aminoethyl)aminocarbonylmethyloxy)phenyl)-1,3-dipropylxanthine: adenosine receptor antagonist | 2.44 | 2 | 0 | ||
| 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole: antineoplastic; activates platelet guanylate cyclase; a radiosensitizing agent and guanylate cyclase activator; structure in first source. lificiguat : A member of the class of indazoles that is 1H-indazole which is substituted by a benzyl group at position 1 and a 5-(hydroxymethyl)-2-furyl group at position 3. It is an activator of soluble guanylate cyclase and inhibits platelet aggregation. | 2.44 | 2 | 0 | aromatic primary alcohol; furans; indazoles | antineoplastic agent; apoptosis inducer; platelet aggregation inhibitor; soluble guanylate cyclase activator; vasodilator agent |
| zardaverine zardaverine: structure given in first source. zardaverine : A pyridazinone derivative in which pyridazin-3(2H)-one is substituted at C-6 with a 4-(difluoromethoxy)-3-methoxyphenyl group. It is a phosphodiesterase inhibitor, selective for PDE3 and 4. | 2.03 | 1 | 0 | organofluorine compound; pyridazinone | anti-asthmatic drug; bronchodilator agent; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; peripheral nervous system drug |
| cortisone acetate Cortisone Acetate: The acetate ester of cortisone that is used mainly for replacement therapy in adrenocortical insufficiency and in the treatment of many allergic and inflammatory disorders. | 2.03 | 1 | 0 | corticosteroid hormone | |
| corticosterone [no description available] | 2.44 | 2 | 0 | 11beta-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(4) steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone | human metabolite; mouse metabolite |
| reserpine Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.. reserpine : An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. | 2.44 | 2 | 0 | alkaloid ester; methyl ester; yohimban alkaloid | adrenergic uptake inhibitor; antihypertensive agent; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; first generation antipsychotic; plant metabolite; xenobiotic |
| procaine hydrochloride Gerovital H3: Contains mainly procaine & small amounts of benzoic acid, potassium metabisulfite & disodium phosphate | 2.03 | 1 | 0 | organic molecular entity | |
| isoproterenol hydrochloride [no description available] | 2.44 | 2 | 0 | catechols | |
| histamine dihydrochloride Ceplene: Tradename for histamine dihydrochloride. | 2.03 | 1 | 0 | ||
| carbachol Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. | 2.03 | 1 | 0 | ammonium salt; carbamate ester | cardiotonic drug; miotic; muscarinic agonist; nicotinic acetylcholine receptor agonist; non-narcotic analgesic |
| spironolactone Spironolactone: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827). spironolactone : A steroid lactone that is 17alpha-pregn-4-ene-21,17-carbolactone substituted by an oxo group at position 3 and an alpha-acetylsulfanyl group at position 7. | 2.44 | 2 | 0 | 3-oxo-Delta(4) steroid; oxaspiro compound; steroid lactone; thioester | aldosterone antagonist; antihypertensive agent; diuretic; environmental contaminant; xenobiotic |
| estrone Hydroxyestrones: Estrone derivatives substituted with one or more hydroxyl groups in any position. They are important metabolites of estrone and other estrogens. | 2.44 | 2 | 0 | 17-oxo steroid; 3-hydroxy steroid; phenolic steroid; phenols | antineoplastic agent; bone density conservation agent; estrogen; human metabolite; mouse metabolite |
| androsterone [no description available] | 2.44 | 2 | 0 | 17-oxo steroid; 3alpha-hydroxy steroid; androstanoid; C19-steroid | androgen; anticonvulsant; human blood serum metabolite; human metabolite; human urinary metabolite; mouse metabolite; pheromone |
| promazine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | |
| pilocarpine hydrochloride pilocarpine hydrochloride : The hydrochloride salt of (+)-pilocarpine, a medication used to treat increased pressure inside the eye and dry mouth. | 2.03 | 1 | 0 | hydrochloride | |
| dimethylphenylpiperazinium iodide Dimethylphenylpiperazinium Iodide: A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction. | 2.44 | 2 | 0 | N-arylpiperazine; organic iodide salt; piperazinium salt; quaternary ammonium salt | nicotinic acetylcholine receptor agonist |
| pentylenetetrazole Pentylenetetrazole: A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.. pentetrazol : An organic heterobicyclic compound that is 1H-tetrazole in which the hydrogens at positions 1 and 5 are replaced by a pentane-1,5-diyl group. A central and respiratory stimulant, it was formerly used for the treatment of cough and other respiratory tract disorders, cardiovascular disorders including hypotension, and pruritis. | 2.03 | 1 | 0 | organic heterobicyclic compound; organonitrogen heterocyclic compound | |
| racepinephrine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| (4-(m-chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium chloride (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride: A drug that selectively activates certain subclasses of muscarinic receptors and also activates postganglionic nicotinic receptors. It is commonly used experimentally to distinguish muscarinic receptor subtypes. | 2.44 | 2 | 0 | ||
| hexamethonium bromide [no description available] | 2.03 | 1 | 0 | ||
| cystamine dihydrochloride [no description available] | 2.03 | 1 | 0 | ||
| cantharidin Cantharidin: A toxic compound, isolated from the Spanish fly or blistering beetle (Lytta (Cantharis) vesicatoria) and other insects. It is a potent and specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.. cantharidin : A monoterpenoid with an epoxy-bridged cyclic dicarboxylic anhydride structure secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. Natural toxin inhibitor of protein phosphatases 1 and 2A. | 2.44 | 2 | 0 | cyclic dicarboxylic anhydride; monoterpenoid | EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; herbicide |
| tetraethylammonium chloride tetraethylammonium chloride : A quarternary ammonium chloride salt in which the cation has four ethyl substituents around the central nitrogen. | 2.44 | 2 | 0 | organic chloride salt; quaternary ammonium salt | potassium channel blocker |
| aspartic acid Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.. aspartic acid : An alpha-amino acid that consists of succinic acid bearing a single alpha-amino substituent. L-aspartic acid : The L-enantiomer of aspartic acid. | 2.03 | 1 | 0 | aspartate family amino acid; aspartic acid; L-alpha-amino acid; proteinogenic amino acid | Escherichia coli metabolite; mouse metabolite; neurotransmitter |
| glutamine Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.. L-glutamine : An optically active form of glutamine having L-configuration.. glutamine : An alpha-amino acid that consists of butyric acid bearing an amino substituent at position 2 and a carbamoyl substituent at position 4. | 2.03 | 1 | 0 | amino acid zwitterion; glutamine family amino acid; glutamine; L-alpha-amino acid; polar amino acid zwitterion; proteinogenic amino acid | EC 1.14.13.39 (nitric oxide synthase) inhibitor; Escherichia coli metabolite; human metabolite; metabolite; micronutrient; mouse metabolite; nutraceutical; Saccharomyces cerevisiae metabolite |
| vincristine [no description available] | 2.03 | 1 | 0 | acetate ester; formamides; methyl ester; organic heteropentacyclic compound; organic heterotetracyclic compound; tertiary alcohol; tertiary amino compound; vinca alkaloid | antineoplastic agent; drug; microtubule-destabilising agent; plant metabolite; tubulin modulator |
| physostigmine Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. | 2.44 | 2 | 0 | carbamate ester; indole alkaloid | antidote to curare poisoning; EC 3.1.1.8 (cholinesterase) inhibitor; miotic |
| apomorphine Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. | 2.03 | 1 | 0 | aporphine alkaloid | alpha-adrenergic drug; antidyskinesia agent; antiparkinson drug; dopamine agonist; emetic; serotonergic drug |
| promethazine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | anti-allergic agent; anticoronaviral agent; antiemetic; antipruritic drug; geroprotector; H1-receptor antagonist; local anaesthetic; sedative |
| bromodeoxyuridine Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. | 2.03 | 1 | 0 | pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent |
| levodopa Levodopa: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.. L-dopa : An optically active form of dopa having L-configuration. Used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease | 2.03 | 1 | 0 | amino acid zwitterion; dopa; L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | allelochemical; antidyskinesia agent; antiparkinson drug; dopaminergic agent; hapten; human metabolite; mouse metabolite; neurotoxin; plant growth retardant; plant metabolite; prodrug |
| methoxamine hydrochloride [no description available] | 2.44 | 2 | 0 | dimethoxybenzene | |
| papaverine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| bretylium tosylate Bretylium Tosylate: An agent that blocks the release of adrenergic transmitters and may have other actions. It was formerly used as an antihypertensive agent, but is now proposed as an anti-arrhythmic.. bretylium tosylate : The tosylate salt of bretylium. It blocks noradrenaline release from the peripheral sympathetic nervous system, and is used in emergency medicine, cardiology, and other specialties for the acute management of ventricular tachycardia and ventricular fibrillation. | 2.44 | 2 | 0 | organosulfonate salt; quaternary ammonium salt | adrenergic antagonist; anti-arrhythmia drug; antihypertensive agent |
| berlition berlition: antioxidant preparation containing alpha-lipoic acid, used in the neuroprotective therapy of chronic brain ischemia for correction of free-radical processes. (R)-lipoic acid : The (R)-enantiomer of lipoic acid. A vitamin-like, C8 thia fatty acid with anti-oxidant properties.. lipoic acid : A heterocyclic thia fatty acid comprising pentanoic acid with a 1,2-dithiolan-3-yl group at the 5-position. | 2.03 | 1 | 0 | dithiolanes; heterocyclic fatty acid; lipoic acid; thia fatty acid | cofactor; nutraceutical; prosthetic group |
| methacholine chloride Methacholine Chloride: A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116) | 2.03 | 1 | 0 | quaternary ammonium salt | |
| androstenedione Androstenedione: A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.. androst-4-ene-3,17-dione : A 3-oxo Delta(4)-steroid that is androst-4-ene substituted by oxo groups at positions 3 and 17. It is a steroid hormone synthesized in the adrenal glands and gonads. | 2.44 | 2 | 0 | 17-oxo steroid; 3-oxo-Delta(4) steroid; androstanoid | androgen; Daphnia magna metabolite; human metabolite; mouse metabolite |
| colchicine (S)-colchicine : A colchicine that has (S)-configuration. It is a secondary metabolite, has anti-inflammatory properties and is used to treat gout, crystal-induced joint inflammation, familial Mediterranean fever, and many other conditions. | 2.44 | 2 | 0 | alkaloid; colchicine | anti-inflammatory agent; gout suppressant; mutagen |
| yohimbine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| gallamine triethiodide Gallamine Triethiodide: A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198) | 2.03 | 1 | 0 | ||
| cycloheximide Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.. cycloheximide : A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus. | 2.03 | 1 | 0 | antibiotic fungicide; cyclic ketone; dicarboximide; piperidine antibiotic; piperidones; secondary alcohol | anticoronaviral agent; bacterial metabolite; ferroptosis inhibitor; neuroprotective agent; protein synthesis inhibitor |
| egtazic acid Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.. ethylene glycol bis(2-aminoethyl)tetraacetic acid : A diether that is ethylene glycol in which the hydrogens of the hydroxy groups have been replaced by 2-[bis(carboxymethyl)amino]ethyl group respectively. | 2.03 | 1 | 0 | diether; tertiary amino compound; tetracarboxylic acid | chelator |
| cycloserine Cycloserine: Antibiotic substance produced by Streptomyces garyphalus.. D-cycloserine : A 4-amino-1,2-oxazolidin-3-one that has R configuration. It is an antibiotic produced by Streptomyces garyphalus or S. orchidaceus and is used as part of a multi-drug regimen for the treatment of tuberculosis when resistance to, or toxicity from, primary drugs has developed. An analogue of D-alanine, it interferes with bacterial cell wall synthesis in the cytoplasm by competitive inhibition of L-alanine racemase (which forms D-alanine from L-alanine) and D-alanine--D-alanine ligase (which incorporates D-alanine into the pentapeptide required for peptidoglycan formation and bacterial cell wall synthesis). | 2.03 | 1 | 0 | 4-amino-1,2-oxazolidin-3-one; organonitrogen heterocyclic antibiotic; organooxygen heterocyclic antibiotic; zwitterion | antiinfective agent; antimetabolite; antitubercular agent; metabolite; NMDA receptor agonist |
| 17-alpha-hydroxyprogesterone 17alpha-hydroxyprogesterone : A 17alpha-hydroxy steroid that is the 17alpha-hydroxy derivative of progesterone. | 2.44 | 2 | 0 | 17alpha-hydroxy-C21-steroid; 17alpha-hydroxy steroid; tertiary alpha-hydroxy ketone | human metabolite; metabolite; mouse metabolite; progestin |
| quinacrine monohydrochloride [no description available] | 2.44 | 2 | 0 | ||
| chlorpromazine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride; phenothiazines | anticoronaviral agent; phenothiazine antipsychotic drug |
| cytarabine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| tryptophan Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.. tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3. | 2.44 | 2 | 0 | erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid zwitterion; L-alpha-amino acid; proteinogenic amino acid; tryptophan zwitterion; tryptophan | antidepressant; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
| lidocaine hydrochloride lidocaine hydrochloride : The anhydrous form of the hydrochloride salt of lidocaine. | 2.44 | 2 | 0 | hydrochloride | anti-arrhythmia drug; local anaesthetic |
| arginine Arginine: An essential amino acid that is physiologically active in the L-form.. arginine : An alpha-amino acid that is glycine in which the alpha-is substituted by a 3-guanidinopropyl group. | 2.03 | 1 | 0 | arginine; glutamine family amino acid; L-alpha-amino acid; proteinogenic amino acid | biomarker; Escherichia coli metabolite; micronutrient; mouse metabolite; nutraceutical |
| rotenone Derris: A plant genus of the family FABACEAE. The root is a source of rotenoids (ROTENONE) and flavonoids. Some species of Pongamia have been reclassified to this genus and some to MILLETTIA. Some species of Deguelia have been reclassified to this genus.. rotenoid : Members of the class of tetrahydrochromenochromene that consists of a cis-fused tetrahydrochromeno[3,4-b]chromene skeleton and its substituted derivatives. The term was originally restricted to natural products, but is now also used to describe semi-synthetic and fully synthetic compounds. | 2.44 | 2 | 0 | organic heteropentacyclic compound; rotenones | antineoplastic agent; metabolite; mitochondrial NADH:ubiquinone reductase inhibitor; phytogenic insecticide; piscicide; toxin |
| synephrine [no description available] | 2.03 | 1 | 0 | ethanolamines; phenethylamine alkaloid; phenols | alpha-adrenergic agonist; plant metabolite |
| pyridostigmine bromide Pyridostigmine Bromide: A cholinesterase inhibitor with a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants. | 2.03 | 1 | 0 | pyridinium salt | |
| imipramine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | antidepressant |
| neostigmine bromide neostigmine bromide : The bromide salt of neostigmine. | 2.03 | 1 | 0 | bromide salt | |
| edrophonium chloride edrophonium chloride : The chloride salt of edrophonium. A reversible inhibitor of cholinesterase with a rapid onset (30-60 seconds after injection) but a short duration of action (5-15 minutes), it is used in myasthenia gravis both diagnostically and to distinguish between under- or over-treatment with other anticholinesterases. It has also been used for the reversal of neuromuscular blockade in anaesthesia, and for the management of poisoning due to tetrodotoxin, a neuromuscular blocking toxin found in puffer fish and other marine animals. | 2.03 | 1 | 0 | chloride salt; quaternary ammonium salt | antidote; diagnostic agent; EC 3.1.1.8 (cholinesterase) inhibitor |
| suramin sodium suramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness. | 2.44 | 2 | 0 | organic sodium salt | angiogenesis inhibitor; antinematodal drug; antineoplastic agent; apoptosis inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; GABA antagonist; GABA-gated chloride channel antagonist; purinergic receptor P2 antagonist; ryanodine receptor agonist; trypanocidal drug |
| pyrazolanthrone pyrazolanthrone: JNK (c-Jun N-terminal kinase) inhibitor; structure in first source. anthra[1,9-cd]pyrazol-6(2H)-one : A member of the class of anthrapyrazoles that is anthra[1,9-cd]pyrazole substituted at position 6 by an oxo group. An inhibitor of c-Jun N-terminal kinase. | 2.44 | 2 | 0 | anthrapyrazole; aromatic ketone; cyclic ketone | antineoplastic agent; c-Jun N-terminal kinase inhibitor; geroprotector |
| methapyrilene hydrochloride methapyrilene hydrochloride : A hydrochloride that is the monohydrochloride salt of methapyrilene. | 2.44 | 2 | 0 | hydrochloride | anti-allergic agent; carcinogenic agent; H1-receptor antagonist; sedative |
| tetrracaine hydrochloride leocaine: a crystal beta-modification of the beta-dimethylaminoethyl ether of n-butylaminobenzoic acid hydrochloride | 2.03 | 1 | 0 | benzoate ester | |
| chelidamic acid [no description available] | 2.03 | 1 | 0 | ||
| 2-chloroadenosine 5-chloroformycin A: structure given in first source | 2.44 | 2 | 0 | purine nucleoside | |
| diphenhydramine hydrochloride Antitussive Agents: Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally.. diphenhydramine hydrochloride : The hydrochloride salt of diphenhydramine. | 2.44 | 2 | 0 | hydrochloride; organoammonium salt | anti-allergic agent; antiemetic; antiparkinson drug; antipruritic drug; H1-receptor antagonist; local anaesthetic; muscarinic antagonist; sedative |
| cysteamine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| propantheline bromide [no description available] | 2.44 | 2 | 0 | xanthenes | |
| hydralazine hydrochloride hydralazine hydrochloride : The hydrochloride salt of hydralazine; a direct-acting vasodilator that is used as an antihypertensive agent. | 2.03 | 1 | 0 | hydrochloride | antihypertensive agent; vasodilator agent |
| ethamivan ethamivan: minor descriptor (65-72); major descriptor (73-86); on-line search BENZAMIDES (66-86); INDEX MEDICUS search BENZAMIDES (65-72); ETHAMIVAN (73-86). etamivan : Phenol substituted at C-2 and C-4 by a methoxy group and an N,N-diethylaminocarbonyl group respectively. A respiratory stimulant drug related to nikethamide, it has now fallen largely into disuse. | 2.03 | 1 | 0 | methoxybenzenes; phenols | |
| pargyline hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| aminophylline Aminophylline: A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.. aminophylline : A mixture comprising of theophylline and ethylenediamine in a 2:1 ratio. | 2.03 | 1 | 0 | mixture | bronchodilator agent; cardiotonic drug |
| azacitidine Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.. 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia. | 2.03 | 1 | 0 | N-glycosyl-1,3,5-triazine; nucleoside analogue | antineoplastic agent |
| orphenadrine hydrochloride orphenadrine hydrochloride : A hydrochloride comprising equimolar amounts of ophenadrine and hydrogen chloride. | 2.44 | 2 | 0 | hydrochloride | antiparkinson drug; H1-receptor antagonist; muscarinic antagonist; muscle relaxant; NMDA receptor antagonist; parasympatholytic |
| betamethasone Betamethasone: A glucocorticoid given orally, parenterally, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p724) | 2.44 | 2 | 0 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; fluorinated steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | anti-asthmatic agent; anti-inflammatory drug; immunosuppressive agent |
| benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(n,n-dimethyl-n-2-propenyl-), dibromide Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide: Proposed cholinesterase inhibitor. | 2.44 | 2 | 0 | ||
| cyproterone acetate [no description available] | 2.44 | 2 | 0 | 20-oxo steroid; 3-oxo-Delta(4) steroid; acetate ester; chlorinated steroid; steroid ester | androgen antagonist; geroprotector; progestin |
| bicuculline Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.. bicuculline : A benzylisoquinoline alkaloid that is 6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinoline which is substituted at the 5-pro-S position by a (6R)-8-oxo-6,8-dihydrofuro[3,4-e][1,3]benzodioxol-6-yl group. A light-sensitive competitive antagonist of GABAA receptors. It was originally identified in 1932 in plant alkaloid extracts and has been isolated from Dicentra cucullaria, Adlumia fungosa, Fumariaceae, and several Corydalis species. | 2.03 | 1 | 0 | benzylisoquinoline alkaloid; isoquinoline alkaloid; isoquinolines | agrochemical; central nervous system stimulant; GABA-gated chloride channel antagonist; GABAA receptor antagonist; neurotoxin |
| kainic acid Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. | 2.03 | 1 | 0 | dicarboxylic acid; L-proline derivative; non-proteinogenic L-alpha-amino acid; pyrrolidinecarboxylic acid | antinematodal drug; excitatory amino acid agonist |
| podophyllotoxin Podophyllum: A genus of poisonous American herbs, family BERBERIDACEAE. The roots yield PODOPHYLLOTOXIN and other pharmacologically important agents. The plant was formerly used as a cholagogue and cathartic. It is different from the European mandrake, MANDRAGORA. | 2.44 | 2 | 0 | furonaphthodioxole; lignan; organic heterotetracyclic compound | antimitotic; antineoplastic agent; keratolytic drug; microtubule-destabilising agent; plant metabolite; tubulin modulator |
| tetrahydrozoline hydrochloride tetrahydrozoline hydrochloride : The hydrochloride salt of tetryzoline. It is used as a nasal decongestant. | 2.44 | 2 | 0 | hydrochloride | nasal decongestant; sympathomimetic agent; vasoconstrictor agent |
| dequalinium chloride dequalinium chloride : An organic chloride salt that is the dichloride salt of dequalinium. | 2.44 | 2 | 0 | organic chloride salt | antifungal agent; antineoplastic agent; antiseptic drug; mitochondrial NADH:ubiquinone reductase inhibitor |
| decamethonium dibromide [no description available] | 2.44 | 2 | 0 | ||
| amitriptyline hydrochloride [no description available] | 2.44 | 2 | 0 | organic tricyclic compound | |
| naphazoline hydrochloride [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| doxylamine succinate [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| carbamylhydrazine monohydrochloride [no description available] | 2.03 | 1 | 0 | organic molecular entity | |
| formestane [no description available] | 2.44 | 2 | 0 | 17-oxo steroid; 3-oxo-Delta(4) steroid; enol; hydroxy steroid | antineoplastic agent; EC 1.14.14.14 (aromatase) inhibitor |
| debrisoquin sulfate [no description available] | 2.03 | 1 | 0 | organic sulfate salt | |
| betaine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| bethanechol chloride bethanechol chloride : The chloride salt of bethanechol. A slowly hydrolysed muscarinic agonist with no nicotinic effects, it is used to increase smooth muscle tone, as in the gastrointestinal tract following abdominal surgery, treatment of gastro-oesophageal reflux disease, and as an alternative to catheterisation in the treatment of non-obstructive urinary retention. | 2.03 | 1 | 0 | carbamate ester; chloride salt; quaternary ammonium salt | muscarinic agonist |
| acetylcysteine N-acetyl-L-cysteine : An N-acetyl-L-amino acid that is the N-acetylated derivative of the natural amino acid L-cysteine. | 2.03 | 1 | 0 | acetylcysteine; L-cysteine derivative; N-acetyl-L-amino acid | antidote to paracetamol poisoning; antiinfective agent; antioxidant; antiviral drug; ferroptosis inhibitor; geroprotector; human metabolite; mucolytic; radical scavenger; vulnerary |
| Mecamylamine hydrochloride [no description available] | 2.44 | 2 | 0 | monoterpenoid | |
| vinblastine [no description available] | 2.03 | 1 | 0 | ||
| cyproheptadine hydrochloride (anhydrous) cyproheptadine hydrochloride (anhydrous) : The hydrochloride salt of cyproheptadine. Note that the drug named cyproheptadine hydrochloride generally refers to cyproheptadine hydrochloride sesquihydrate. | 2.44 | 2 | 0 | hydrochloride | |
| 5 alpha-androstane-3 alpha,17 beta-diol 5alpha-androstane-3alpha,17beta-diol : The 5alpha-stereoisomer of androstane-3alpha,17beta-diol. | 2.03 | 1 | 0 | androstane-3alpha,17beta-diol | Daphnia magna metabolite; human metabolite |
| pimozide Pimozide: A diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to HALOPERIDOL for the suppression of vocal and motor tics in patients with Tourette syndrome. Although the precise mechanism of action is unknown, blockade of postsynaptic dopamine receptors has been postulated. (From AMA Drug Evaluations Annual, 1994, p403). pimozide : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which one of the nitrogens is substituted by a piperidin-4-yl group, which in turn is substituted on the nitrogen by a 4,4-bis(p-fluorophenyl)butyl group. | 2.44 | 2 | 0 | benzimidazoles; heteroarylpiperidine; organofluorine compound | antidyskinesia agent; dopaminergic antagonist; first generation antipsychotic; H1-receptor antagonist; serotonergic antagonist |
| azetidyl-2-carboxylic acid azetidyl-2-carboxylic acid: a proline analog (with 4-membered ring in place of 5); a toxic non-protein amino acid that is misincorporated into protein in place of proline; induces nonfunctional heat-shock proteins; inhibits acquired thermotolerance; RN given refers to (L)-isomer; found in beets and Liliaceae. (S)-azetidine-2-carboxylic acid : The (S)-enantiomer of azetidine-2-carboxylic acid.. azetidinecarboxylic acid : A member of the class of azetidines that is azetidine substituted by at least one carboxy group at unspecified position. | 2.03 | 1 | 0 | azetidine-2-carboxylic acid | |
| muscarine [no description available] | 2.03 | 1 | 0 | ||
| antazoline hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| doxifluridine doxifluridine : A pyrimidine 5'-deoxyribonucleoside that is 5-fluorouridine in which the hydroxy group at the 5' position is replaced by a hydrogen. It is an oral prodrug of the antineoplastic agent 5-fluorouracil. Designed to circumvent the rapid degradation of 5-fluorouracil by dihydropyrimidine dehydrogenase in the gut wall, it is converted into 5-fluorouracil in the presence of pyrimidine nucleoside phosphorylase. | 2.03 | 1 | 0 | organofluorine compound; pyrimidine 5'-deoxyribonucleoside | antimetabolite; antineoplastic agent; prodrug |
| meclofenoxate hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| clonidine hydrochloride [no description available] | 2.03 | 1 | 0 | dichlorobenzene | |
| beclomethasone [no description available] | 2.44 | 2 | 0 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; chlorinated steroid; corticosteroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | anti-asthmatic drug; anti-inflammatory drug |
| buthionine sulfoximine Buthionine Sulfoximine: A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7). 2-amino-4-(S-butylsulfonimidoyl)butanoic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group carries an oxo, imino and butyl groups.. S-butyl-DL-homocysteine (S,R)-sulfoximine : A sulfoximide that is the sulfoximine derivative of an analogue of DL-methionine in which the S-methyl group is replaced by S-butyl. | 2.44 | 2 | 0 | diastereoisomeric mixture; homocysteines; non-proteinogenic alpha-amino acid; sulfoximide | EC 6.3.2.2 (glutamate--cysteine ligase) inhibitor; ferroptosis inducer |
| mexiletine hydrochloride mexiletine hydrochloride : A hydrochloride composed of equimolar amounts of mexiletine and hydrogen chloride. | 2.44 | 2 | 0 | hydrochloride | anti-arrhythmia drug |
| cyclophosphamide cyclophosphamide hydrate : The monohydrate of cyclophosphamide. | 2.03 | 1 | 0 | hydrate | alkylating agent; antineoplastic agent; carcinogenic agent; immunosuppressive agent |
| suxamethonium chloride succinylcholine chloride (anhydrous) : A chloride salt in which the negative charge of the chloride ions is balanced by succinylcholine dications. | 2.03 | 1 | 0 | chloride salt | muscle relaxant |
| cyclobenzaprine hydrochloride cyclobenzaprine hydrochloride : The hydrochloride salt of cyclobenzaprine. A centrally acting skeletal muscle relaxant, it is used in the symptomatic treatment of painful muscle spasm. | 2.44 | 2 | 0 | hydrochloride | antidepressant; muscle relaxant |
| n-methylaspartate N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).. N-methyl-D-aspartic acid : An aspartic acid derivative having an N-methyl substituent and D-configuration. | 2.03 | 1 | 0 | amino dicarboxylic acid; D-alpha-amino acid; D-aspartic acid derivative; secondary amino compound | neurotransmitter agent |
| 3-deazaadenosine 3-deazaadenosine: RN given refers to parent cpd. | 2.44 | 2 | 0 | ||
| metoclopramide hydrochloride metoclopramide hydrochloride : A hydrate that is the monohydrate form of metoclopramide monohydrochloride. | 2.44 | 2 | 0 | ||
| isoetharine mesylate [no description available] | 2.44 | 2 | 0 | ||
| zalcitabine Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.. zalcitabine : A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase. | 2.03 | 1 | 0 | pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
| propionylpromazine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| camptothecin NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source | 2.44 | 2 | 0 | delta-lactone; pyranoindolizinoquinoline; quinoline alkaloid; tertiary alcohol | antineoplastic agent; EC 5.99.1.2 (DNA topoisomerase) inhibitor; genotoxin; plant metabolite |
| nsc-145,668 [no description available] | 2.03 | 1 | 0 | hydrochloride | antimetabolite; antineoplastic agent |
| clodronic acid Clodronic Acid: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.. clodronic acid : An organochlorine compound that is methylene chloride in which both hydrogens are replaced by phosphonic acid groups. It inhibits bone resorption and soft tissue calcification, and is used (often as the disodium salt tetrahydrate) as an adjunct in the treatment of severe hypercalcaemia associated with malignancy, and in the management of osteolytic lesions and bone pain associated with skeletal metastases. | 2.03 | 1 | 0 | 1,1-bis(phosphonic acid); one-carbon compound; organochlorine compound | antineoplastic agent; bone density conservation agent |
| benserazide hydrochloride benserazide hydrochloride : A hydrochloride that is the monohydrochloride salt of benserazide. An aromatic-L-amino-acid decarboxylase inhibitor (DOPA decarboxylase inhibitor) that does not enter the central nervous system, it is used as an adjunct to levodopa in the treatment of parkinsonism. By preventing the conversion of levodopa to dopamine in the periphery, it causes an increase in the amount of levodopa reaching the central nervous system and so reduces the required dose. Benserazide hydrochloride has no antiparkinson actions when given alone. | 2.44 | 2 | 0 | hydrochloride | antiparkinson drug; dopaminergic agent; EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor |
| pancuronium bromide pancuronium bromide : A bromide salt consisting of two bromide ions and one pancuronium dication. | 2.44 | 2 | 0 | bromide salt | cholinergic antagonist; muscle relaxant; nicotinic antagonist |
| tetradecanoylphorbol acetate Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.. phorbol ester : Esters of phorbol, originally found in croton oil (from Croton tiglium, of the family Euphorbiaceae). A number of phorbol esters possess activity as tumour promoters and activate the mechanisms associated with cell growth. Some of these are used in experiments as activators of protein kinase C.. phorbol 13-acetate 12-myristate : A phorbol ester that is phorbol in which the hydroxy groups at the cyclopropane ring juction (position 13) and the adjacent carbon (position 12) have been converted into the corresponding acetate and myristate esters. It is a major active constituent of the seed oil of Croton tiglium. It has been used as a tumour promoting agent for skin carcinogenesis in rodents and is associated with increased cell proliferation of malignant cells. However its function is controversial since a decrease in cell proliferation has also been observed in several cancer cell types. | 2.44 | 2 | 0 | acetate ester; diester; phorbol ester; tertiary alpha-hydroxy ketone; tetradecanoate ester | antineoplastic agent; apoptosis inducer; carcinogenic agent; mitogen; plant metabolite; protein kinase C agonist; reactive oxygen species generator |
| danazol Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. | 2.44 | 2 | 0 | 17beta-hydroxy steroid; terminal acetylenic compound | anti-estrogen; estrogen antagonist; geroprotector |
| metergoline Metergoline: A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy.. metergoline : An ergoline alkaloid that is the N-benzyloxycarbonyl derivative of lysergamine. A 5-HT2 antagonist. Also 5-HT1 antagonist and 5-HT1D ligand. Has moderate affinity for 5-HT6 and high affinity for 5-HT7. | 2.44 | 2 | 0 | carbamate ester; ergoline alkaloid | dopamine agonist; geroprotector; serotonergic antagonist |
| lisuride Lisuride: An ergot derivative that acts as an agonist at dopamine D2 receptors (DOPAMINE AGONISTS). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (SEROTONIN RECEPTOR AGONISTS). | 2.03 | 1 | 0 | monocarboxylic acid amide | antidyskinesia agent; antiparkinson drug; dopamine agonist; serotonergic agonist |
| disopyramide phosphate [no description available] | 2.44 | 2 | 0 | organoammonium phosphate | |
| 2-bromoergocryptine mesylate [no description available] | 2.05 | 1 | 0 | methanesulfonate salt | antiparkinson drug |
| bromocriptine Bromocriptine: A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. | 2.03 | 1 | 0 | indole alkaloid | antidyskinesia agent; antiparkinson drug; dopamine agonist; hormone antagonist |
| ergocristine ergocristine: an ergot alkaloid; one of the three components of ergotoxine; has alpha blocking action, stimulates smooth muscles & antagonizes serotonin; used as oxytocic & in peripheral disorders; minor descriptor (77-86); on-line & INDEX MEDICUS search EROLINES (77-86); RN given refers to ((5'alpha)-isomer). ergocristine : Ergotaman bearing benzyl, hydroxy, and isopropyl groups at the 5', 12' and 2' positions, respectively, and oxo groups at positions 3', 6', and 18. It is a natural ergot alkaloid. | 2.03 | 1 | 0 | ergot alkaloid | |
| triamcinolone Triamcinolone: A glucocorticoid given, as the free alcohol or in esterified form, orally, intramuscularly, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. (From Martindale, The Extra Pharmacopoeia, 30th ed, p739). triamcinolone : A C21-steroid hormone that is 1,4-pregnadiene-3,20-dione carrying four hydroxy substituents at positions 11beta, 16alpha, 17alpha and 21 as well as a fluoro substituent at position 9. Used in the form of its 16,17-acetonide to treat various skin infections. | 2.03 | 1 | 0 | 11beta-hydroxy steroid; 16alpha-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(4) steroid; C21-steroid hormone; fluorinated steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | anti-allergic agent; anti-inflammatory drug |
| zidovudine Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.. zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase. | 2.03 | 1 | 0 | azide; pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
| paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL). | 2.44 | 2 | 0 | taxane diterpenoid; tetracyclic diterpenoid | antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent |
| buspirone hydrochloride buspirone hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of buspirone and hydrogen chloride. | 2.44 | 2 | 0 | hydrochloride | anxiolytic drug; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; sedative; serotonergic agonist |
| etoposide [no description available] | 2.44 | 2 | 0 | beta-D-glucoside; furonaphthodioxole; organic heterotetracyclic compound | antineoplastic agent; DNA synthesis inhibitor |
| propafenone hydrochloride propafenone hydrochloride : A hydrochloride that is the monohydrochloride salt of propafenone. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used in the management of supraventricular and ventricular arrhythmias. | 2.44 | 2 | 0 | hydrochloride | anti-arrhythmia drug |
| etazolate hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| butaclamol [no description available] | 2.03 | 1 | 0 | amino alcohol; organic heteropentacyclic compound; tertiary alcohol; tertiary amino compound | dopaminergic antagonist |
| ribavirin Rebetron: Rebetron is tradename | 2.44 | 2 | 0 | 1-ribosyltriazole; aromatic amide; monocarboxylic acid amide; primary carboxamide | anticoronaviral agent; antiinfective agent; antimetabolite; antiviral agent; EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor |
| zinterol [no description available] | 3.38 | 2 | 0 | ||
| carbidopa [no description available] | 2.44 | 2 | 0 | catechols; hydrate; hydrazines; monocarboxylic acid | antidyskinesia agent; antiparkinson drug; dopaminergic agent; EC 4.1.1.28 (aromatic-L-amino-acid decarboxylase) inhibitor |
| cephradine Cephradine: A semi-synthetic cephalosporin antibiotic.. cephradine : A first-generation cephalosporin antibiotic with a methyl substituent at position 3, and a (2R)-2-amino-2-cyclohexa-1,4-dien-1-ylacetamido substituent at position 7, of the cephem skeleton. | 2.03 | 1 | 0 | beta-lactam antibiotic allergen; cephalosporin | antibacterial drug |
| methyldopa Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.. alpha-methyl-L-dopa : A derivative of L-tyrosine having a methyl group at the alpha-position and an additional hydroxy group at the 3-position on the phenyl ring. | 2.03 | 1 | 0 | L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | alpha-adrenergic agonist; antihypertensive agent; hapten; peripheral nervous system drug; sympatholytic agent |
| lonidamine lonidamine: structure. lonidamine : A member of the class of indazoles that is 1H-indazole that is substituted at positions 1 and 3 by 2,4-dichlorobenzyl and carboxy groups, respectively. | 2.03 | 1 | 0 | dichlorobenzene; indazoles; monocarboxylic acid | antineoplastic agent; antispermatogenic agent; EC 2.7.1.1 (hexokinase) inhibitor; geroprotector |
| dexibuprofen dexibuprofen: structure in first source | 2.03 | 1 | 0 | ibuprofen | non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| quisqualic acid Quisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis. | 2.03 | 1 | 0 | non-proteinogenic alpha-amino acid | |
| pirfenidone pirfenidone : A pyridone that is 2-pyridone substituted at positions 1 and 5 by phenyl and methyl groups respectively. An anti-inflammatory drug used for the treatment of idiopathic pulmonary fibrosis. | 2.03 | 1 | 0 | pyridone | antipyretic; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| flecainide acetate flecainide acetate : An acetate salt obtained by combining flecainide with one molar equivalent of acetic acid. An antiarrhythmic agent used to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart). | 2.44 | 2 | 0 | acetate salt | anti-arrhythmia drug |
| nicardipine hydrochloride [no description available] | 2.44 | 2 | 0 | dihydropyridine | geroprotector |
| idarubicin Idarubicin: An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA. | 2.44 | 2 | 0 | anthracycline antibiotic; deoxy hexoside; monosaccharide derivative | |
| captopril Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.. captopril : A L-proline derivative in which L-proline is substituted on nitrogen with a (2S)-2-methyl-3-sulfanylpropanoyl group. It is used as an anti-hypertensive ACE inhibitor drug. | 2.03 | 1 | 0 | alkanethiol; L-proline derivative; N-acylpyrrolidine; pyrrolidinemonocarboxylic acid | antihypertensive agent; EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor |
| terazosin hydrochloride anhydrous [no description available] | 2.44 | 2 | 0 | ||
| pergolide mesylate pergolide mesylate : A methanesulfonate salt obtained from pergolide by mixing eqimolar amount of pergolide and methanesulfonic acid. A dopamine D2 receptor agonist which also has D1 and D2 agonist properties, it is used in the management of Parkinson's disease, although it was withdrawn from the U.S. and Canadian markets in 2007 due to an increased risk of cardiac valve dysfunction. | 2.44 | 2 | 0 | methanesulfonate salt | antiparkinson drug; dopamine agonist; geroprotector |
| ranitidine hydrochloride label : A role played by a part of a molecular entity distinguishable by the observer but not by the system and used to identify a tracer. | 2.03 | 1 | 0 | ||
| colforsin Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. | 2.03 | 1 | 0 | acetate ester; cyclic ketone; labdane diterpenoid; organic heterotricyclic compound; tertiary alpha-hydroxy ketone; triol | adenylate cyclase agonist; anti-HIV agent; antihypertensive agent; plant metabolite; platelet aggregation inhibitor; protein kinase A agonist |
| cefaclor anhydrous Cefaclor: Semisynthetic, broad-spectrum antibiotic derivative of CEPHALEXIN.. cefaclor : A cephalosporin bearing chloro and (R)-2-amino-2-phenylacetamido groups at positions 3 and 7, respectively, of the cephem skeleton. | 2.03 | 1 | 0 | cephalosporin | antibacterial drug; drug allergen |
| alo 2145 apraclonidine hydrochloride : The hydrochloride salt of apraclonidine. | 2.03 | 1 | 0 | hydrochloride | alpha-adrenergic agonist; antiglaucoma drug |
| enoximone Enoximone: A selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with CONGESTIVE HEART FAILURE. | 2.03 | 1 | 0 | aromatic ketone | |
| quinpirole Quinpirole: A dopamine D2/D3 receptor agonist.. quinpirole : A pyrazoloquinoline that is (4aR,8aR)-4,4a,5,6,7,8,8a,9-octahydro-1H-pyrazolo[3,4-g]quinoline substituted by a propyl group at position 5. It acts as a dopamine agonist. | 2.13 | 1 | 0 | pyrazoloquinoline | dopamine agonist |
| atomoxetine atomoxetine : A secondary amino compound having methyl and 3-(2-methylphenoxy)-3-phenylpropan-1-yl substituents. | 2.74 | 3 | 0 | aromatic ether; secondary amino compound; toluenes | adrenergic uptake inhibitor; antidepressant; environmental contaminant; xenobiotic |
| raloxifene hydrochloride Raloxifene Hydrochloride: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.. raloxifene hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of raloxifene and hydrogen chloride. | 2.44 | 2 | 0 | hydrochloride | bone density conservation agent; estrogen antagonist; estrogen receptor modulator |
| mifepristone Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary CUSHING SYNDROME. | 2.44 | 2 | 0 | 3-oxo-Delta(4) steroid; acetylenic compound; tertiary amino compound | abortifacient; contraceptive drug; hormone antagonist; synthetic oral contraceptive |
| quinpirole hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| imazodan imazodan: RN & structure given in first source; | 2.03 | 1 | 0 | ||
| salmeterol xinafoate Salmeterol Xinafoate: A selective ADRENERGIC BETA-2 RECEPTOR agonist that functions as a BRONCHODILATOR when administered by inhalation. It is used to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE. | 2.05 | 1 | 0 | naphthoic acid | |
| finasteride Finasteride: An orally active 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE inhibitor. It is used as a surgical alternative for treatment of benign PROSTATIC HYPERPLASIA.. finasteride : An aza-steroid that is a synthetic drug for the treatment of benign prostatic hyperplasia. | 2.05 | 1 | 0 | 3-oxo steroid; aza-steroid; delta-lactam | androgen antagonist; antihyperplasia drug; EC 1.3.1.22 [3-oxo-5alpha-steroid 4-dehydrogenase (NADP(+))] inhibitor |
| mibefradil dihydrochloride [no description available] | 2.44 | 2 | 0 | ||
| eliprodil 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol : A member of the class of piperidines that is piperidine substituted by a 2-(4-chlorophenyl)-2-hydroxyethyl group at position 1 and by a 4-fluorobenzyl group at position 4. | 2.05 | 1 | 0 | monochlorobenzenes; monofluorobenzenes; piperidines; secondary alcohol; tertiary amino compound | |
| aptiganel hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| adenosine quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | 2.03 | 1 | 0 | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| phenelzine sulfate [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| fluoxetine hydrochloride fluoxetine hydrochloride : A racemate comprising equimolar amounts of (R)- and (S)-fluoxetine hydrochloride. A selective serotonin reuptake inhibitor (SSRI), it is used for the treatment of depression (and the depressive phase of bipolar disorder), bullimia nervosa, and obsessive-compulsive disorder. | 2.44 | 2 | 0 | hydrochloride; N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine | |
| propranolol hydrochloride Inderex: combination of above cpds; used in treatment of hypertension | 2.44 | 2 | 0 | hydrochloride | |
| bupropion hydrochloride [no description available] | 2.44 | 2 | 0 | aromatic ketone | |
| diltiazem hydrochloride Carex: fluoride (1.8%) containing varnish; no further information available 8/91. diltiazem hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of diltiazem and hydrogen chloride. A calcium-channel blocker and vasodilator, it is used in the management of angina pectoris and hypertension. | 2.03 | 1 | 0 | hydrochloride | antihypertensive agent; calcium channel blocker; vasodilator agent |
| trazodone hydrochloride Triticum: A plant genus of the family POACEAE that is the source of EDIBLE GRAIN. A hybrid with rye (SECALE CEREALE) is called TRITICALE. The seed is ground into FLOUR and used to make BREAD, and is the source of WHEAT GERM AGGLUTININS.. trazodone hydrochloride : A hydrochloride salt prepared from equimolar amounts of trazodone and hydrogen chloride. | 2.44 | 2 | 0 | hydrochloride | adrenergic antagonist; antidepressant; H1-receptor antagonist; sedative; serotonin uptake inhibitor |
| verapamil hydrochloride verapamil hydrochloride : A racemate comprising equimolar amounts of dexverapamil hydrochloride and (S)-verapamil hydrochloride. | 2.44 | 2 | 0 | ||
| doxazosin mesylate Cardura: Trade name in United States. | 2.44 | 2 | 0 | methanesulfonate salt | geroprotector |
| terfenadine [no description available] | 2.44 | 2 | 0 | diarylmethane | |
| sertraline hydrochloride sertraline hydrochloride : A hydrochloride resulting from the reaction of equimolar amounts of sertraline and hydrogen chloride. A selective serotonin-reuptake inhibitor (SSRI), it is administered orally as an antidepressant for the treatment of depression, obsessive-compulsive disorder, panic disorder and post-traumatic stress disorder. | 2.05 | 1 | 0 | hydrochloride | antidepressant; serotonin uptake inhibitor |
| carmoterol carmoterol: CHF4226.01 and CHF4232.01 are diastereoisomers; structure in first source | 2.05 | 1 | 0 | ||
| amantadine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | antiviral agent; dopamine agonist; NMDA receptor antagonist |
| mevastatin mevastatin: antifungal metabolite from Penicillium brevicopactum; potent inhibitory activity to sterol synthesis; structure. mevastatin : A carboxylic ester that is pravastatin that is lacking the allylic hydroxy group. A hydroxymethylglutaryl-CoA reductase inhibitor (statin) isolated from Penicillium citrinum and from Penicillium brevicompactum, its clinical use as a lipid-regulating drug ceased following reports of toxicity in animals. | 2.03 | 1 | 0 | 2-pyranones; carboxylic ester; hexahydronaphthalenes; polyketide; statin (naturally occurring) | antifungal agent; apoptosis inducer; EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor; fungal metabolite; Penicillium metabolite |
| chloroquine diphosphate [no description available] | 2.44 | 2 | 0 | ||
| dobutamine hydrochloride dobutamine hydrochloride : The hydrochloride salt of dobutamine. A beta1-adrenergic receptor agonist that has cardiac stimulant action without evoking vasoconstriction or tachycardia, it is used to increase the contractility of the heart in the management of acute heart failure. | 2.44 | 2 | 0 | hydrochloride | beta-adrenergic agonist; cardiotonic drug; sympathomimetic agent |
| desipramine hydrochloride desipramine hydrochloride : The hydrochloride salt of desipramine. | 2.44 | 2 | 0 | hydrochloride | drug allergen |
| dopamine hydrochloride P 498: structure in first source; do not confuse with dopamine chloride, also known as P 498 | 2.44 | 2 | 0 | catecholamine | |
| proadifen hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| 4-nitrobenzylthioinosine 4-nitrobenzylthioinosine: inhibitor of nucleoside transport; acts on ENT1 | 2.44 | 2 | 0 | purine nucleoside | |
| metrifudil [no description available] | 2.03 | 1 | 0 | ||
| rutecarpine rutacarpine: from Evodia rutaecarpa; an ingredient in zhuyu hewei zhitong capsules | 2.44 | 2 | 0 | beta-carbolines | |
| trihexyphenidyl hydrochloride [no description available] | 2.44 | 2 | 0 | aralkylamine | |
| thioridazine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | first generation antipsychotic; geroprotector |
| procainamide hydrochloride procainamide hydrochloride : A hydrochloride which has procainamide as the amino component. | 2.03 | 1 | 0 | hydrochloride | anti-arrhythmia drug |
| siquil [no description available] | 2.44 | 2 | 0 | hydrochloride | anticoronaviral agent |
| sotalol hydrochloride sotalol hydrochloride : A hydrochloride salt that is the monohydrochloride of sotalol. It has both beta-adrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. It is used (usually as the hydrochloride salt) for the management of ventricular and supraventricular arrhythmias. | 2.03 | 1 | 0 | hydrochloride | anti-arrhythmia drug; beta-adrenergic antagonist |
| oxymetazoline hydrochloride oxymetazoline hydrochloride : A hydrochloride salt resulting from the reaction of equimolar quantities of oxymetazoline and hydrogen chloride. A direct-acting sympathomimetic with marked alpha-adrenergic activity, it is a vasoconstrictor that is used to relieve nasal congestion. | 2.44 | 2 | 0 | hydrochloride | alpha-adrenergic agonist; nasal decongestant; sympathomimetic agent; vasoconstrictor agent |
| alprenolol hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | |
| 2-methoxyestradiol 2-methoxy-17beta-estradiol : A 17beta-hydroxy steroid, being 17beta-estradiol methoxylated at C-2. | 2.44 | 2 | 0 | 17beta-hydroxy steroid; 3-hydroxy steroid | angiogenesis modulating agent; antimitotic; antineoplastic agent; human metabolite; metabolite; mouse metabolite |
| fluphenazine hydrochloride [no description available] | 2.44 | 2 | 0 | phenothiazines | anticoronaviral agent |
| tryptamine monohydrochloride [no description available] | 2.44 | 2 | 0 | ||
| clomipramine hydrochloride clomipramine hydrochloride : A hydrochloride resulting from the reaction of equimolar amounts of clomipramine and hydrogen chloride. One of the more sedating tricyclic antidepressants, it is used for the treatment of depression as well as obsessive-compulsive disorder and phobias. | 2.44 | 2 | 0 | hydrochloride | anticoronaviral agent; antidepressant; serotonergic antagonist; serotonergic drug |
| amiloride hydrochloride amiloride hydrochloride dihydrate : A hydrate that is the dihydrate of amiloride hydrochloride. | 2.44 | 2 | 0 | hydrate | diuretic; sodium channel blocker |
| prazosin hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | |
| mianserin hydrochloride mianserin hydrochloride : The hydrochloride salt of mianserin, a tetracyclic compound with antidepressant effects. | 2.44 | 2 | 0 | hydrochloride | geroprotector |
| lomefloxacin hydrochloride lomefloxacin hydrochloride : The hydrochloride salt of lomefloxacin. It is administered by mouth to treat bacterial infections including bronchitis and urinary tract infections. It is also used topically as eye drops for the treatment of bacterial conjunctivitis, and as ear drops for the treatment of otitis externa and otitis media. | 2.44 | 2 | 0 | hydrochloride | antimicrobial agent; antitubercular agent; photosensitizing agent |
| fenspiride hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| nilverm [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| sanguinarine chloride [no description available] | 2.44 | 2 | 0 | ||
| ropinirole hydrochloride [no description available] | 2.44 | 2 | 0 | indoles | |
| plasmenylserine plasmenylserine: RN given refers to (L)-isomer. O-phospho-L-serine : The L-enantiomer of O-phosphoserine.. O-phosphoserine : A serine derivative that is serine substituted at the oxygen atom by a phosphono group. | 2.03 | 1 | 0 | O-phosphoserine | EC 1.4.7.1 [glutamate synthase (ferredoxin)] inhibitor; EC 2.5.1.49 (O-acetylhomoserine aminocarboxypropyltransferase) inhibitor; EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| 5-aminovaleric acid hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| n-acetyltryptamine N-acetyltryptamine: antagonizes the melatonin-induced inhibition of dopamine release from retina; RN given refers to parent cpd. N-acetyltryptamine : A tryptamine compound having an acetyl substituent attached to the side-chain amino function. | 2.03 | 1 | 0 | acetamides; indoles | |
| D-serine [no description available] | 2.03 | 1 | 0 | D-alpha-amino acid; serine zwitterion; serine | Escherichia coli metabolite; human metabolite; NMDA receptor agonist |
| dihydroergotamine mesylate dihydroergotamine mesylate : The methanesulfonic acid salt of dihydroergotamine, a semisynthetic ergot alkaloid with weaker oxytocic and vasoconstrictor properties than ergotamine. Both the mesylate and the tartrate salts are used for the treatment of migraine and orthostatic hypotension. | 2.44 | 2 | 0 | methanesulfonate salt | non-narcotic analgesic; serotonergic agonist; vasoconstrictor agent |
| ranolazine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| loxapine succinate [no description available] | 2.44 | 2 | 0 | succinate salt | geroprotector |
| guanfacine hydrochloride [no description available] | 2.44 | 2 | 0 | acetamides | geroprotector |
| pirenzepine dihydrochloride [no description available] | 2.03 | 1 | 0 | hydrochloride | |
| labetalol hydrochloride [no description available] | 2.44 | 2 | 0 | salicylamides | |
| acecainide hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| loperamide hydrochloride loperamide hydrochloride : A hydrochloride obtained by combining loperamide with one equivalent of hydrochloric acid. Used for treatment of diarrhoea resulting from gastroenteritis or inflammatory bowel disease. | 2.44 | 2 | 0 | hydrochloride | anticoronaviral agent; antidiarrhoeal drug; mu-opioid receptor agonist |
| maprotiline hydrochloride [no description available] | 2.44 | 2 | 0 | anthracenes | |
| protoporphyrin ix, disodium salt [no description available] | 2.03 | 1 | 0 | ||
| opipramol hydrochloride [no description available] | 2.05 | 1 | 0 | ||
| siguazodan [no description available] | 2.03 | 1 | 0 | pyridazinone | |
| 3-octadecanamido-2-ethoxypropylphosphocholine 3-octadecanamido-2-ethoxypropylphosphocholine: anti-HIV agent; RN & structure given in first source | 2.03 | 1 | 0 | ||
| chelerythrine chloride [no description available] | 2.44 | 2 | 0 | ||
| tosyllysine chloromethyl ketone [no description available] | 2.44 | 2 | 0 | ||
| 5-(n-methyl-n-isobutyl)amiloride 5-(N-methyl-N-isobutyl)amiloride: inhibitor of the Na+-H+ antiporter | 2.44 | 2 | 0 | ||
| 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride : A hydrochloride salt prepared from anileridine and two molar equivalents of hydrogen chloride. | 2.44 | 2 | 0 | hydrochloride | EC 2.7.11.13 (protein kinase C) inhibitor |
| amperozide hydrochloride amperozide hydrochloride : The hydrochloride salt of amperozide. | 2.44 | 2 | 0 | hydrochloride | anxiolytic drug; dopamine uptake inhibitor; geroprotector; second generation antipsychotic; serotonergic antagonist |
| pyrrolidine dithiocarbamic acid [no description available] | 2.44 | 2 | 0 | ||
| agroclavine agroclavine: structure. agroclavine : An ergot alkaloid that is ergoline which contains a double bond between positions 8 and 9, and which is substituted by methyl groups at positions 6 and 8. | 2.03 | 1 | 0 | ergot alkaloid | |
| s-methylisothiourea sulfate [no description available] | 2.03 | 1 | 0 | ||
| p-Aminobenzamidine dihydrochloride [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| benzamidine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| ketorolac tromethamine Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.. ketorolac tromethamine : An organoammonium salt resulting from the mixture of equimolar amounts of ketorolac and tromethamine (tris). It has potent non-sedating analgesic and moderate anti-inflammatory effects. It is used in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. | 2.03 | 1 | 0 | organoammonium salt | analgesic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor |
| methionine sulfoximine L-methionine sulfoximine : A methionine sulfoximine in which the amino group has S-stereochemistry. | 2.03 | 1 | 0 | L-alpha-amino acid zwitterion; L-methionine derivative; methionine sulfoximine; non-proteinogenic L-alpha-amino acid | EC 6.3.1.2 (glutamate--ammonia ligase) inhibitor; geroprotector |
| tretazicar tretazicar: minor descriptor (75-84); on-line & Index Medicus search AZIRIDINES (75-84) | 2.03 | 1 | 0 | ||
| carbetapentane citrate [no description available] | 2.44 | 2 | 0 | carbonyl compound | |
| phentolamine mesylate [no description available] | 2.44 | 2 | 0 | ||
| mephentermine sphinganine : A 2-aminooctadecane-1,3-diol having (2S,3R)-configuration. | 2.44 | 2 | 0 | 2-aminooctadecane-1,3-diol | EC 2.7.11.13 (protein kinase C) inhibitor; human metabolite; mouse metabolite |
| oxybutynin hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | |
| nimustine nimustine hydrochloride : A hydrochloride obtained by combining nimustine with one equivalent of hydrochloric acid. An antineoplastic agent especially effective against malignant brain tumors. | 2.03 | 1 | 0 | hydrochloride | antineoplastic agent |
| cordium bepridil hydrochloride monohydrate : The hydrochloride monohydrate of bepridril. | 2.03 | 1 | 0 | hydrate; hydrochloride | |
| L-2-aminoadipic acid L-2-aminoadipic acid : The L-enantiomer of 2-aminoadipic acid. | 2.03 | 1 | 0 | 2-aminoadipic acid | Escherichia coli metabolite; human metabolite |
| prilocaine hydrochloride prilocaine hydrochloride : The monohydrochloride salt of prilocaine. | 2.44 | 2 | 0 | hydrochloride | local anaesthetic |
| mor-14 N-methyldeoxynojirimycin: glucosidase inhibitor | 2.03 | 1 | 0 | hydroxypiperidine; piperidine alkaloid; tertiary amino compound | anti-HIV agent; cardioprotective agent; EC 3.2.1.20 (alpha-glucosidase) inhibitor; plant metabolite |
| brexanolone brexanolone: a mixture of allopregnanolone and sulfobutylether‐beta‐cyclodextrin for treatment of postpartum depression. brexanolone : A 3-hydroxy-5alpha-pregnan-20-one in which the hydroxy group at position 3 has alpha-configuration. It is a metabolite of the sex hormone progesterone and used for the treatment of postpartum depression in women. | 2.44 | 2 | 0 | 3-hydroxy-5alpha-pregnan-20-one | antidepressant; GABA modulator; human metabolite; intravenous anaesthetic; sedative |
| phenylisopropyladenosine [no description available] | 2.03 | 1 | 0 | aromatic amine; benzenes; hydrocarbyladenosine; purine nucleoside; secondary amino compound | adenosine A1 receptor agonist; neuroprotective agent |
| hexamethonium chloride [no description available] | 2.03 | 1 | 0 | ||
| 6-(4-nitrobenzylthio)guanosine 6-(4-nitrobenzylthio)guanosine: inhibitor of nucleoside transport | 2.44 | 2 | 0 | ||
| 3-aminopropylphosphonic acid 3-aminopropylphosphonic acid: RN given refers to parent cpd; structure. (3-aminopropyl)phosphonic acid : A phosphonic acid in which the hydrogen attached to the phosphorus of phosphonic acid is substituted by a 3-aminopropyl group. It is a partial agonist of GABAB receptors. | 2.03 | 1 | 0 | phosphonic acids; primary amino compound; zwitterion | GABAB receptor agonist |
| 5'-n-methylcarboxamideadenosine 5'-N-methylcarboxamideadenosine: RN given refers to (beta-D)-isomer | 2.03 | 1 | 0 | ||
| 3,7-dimethyl-1-propargylxanthine 3,7-dimethyl-1-propargylxanthine: potent & selective in vivo antagonist of adenosine analogs | 2.03 | 1 | 0 | ||
| zpck ZPCK: alkylates histidine residue at active center of bovine chymotrypsin | 2.44 | 2 | 0 | ||
| n(6)-phenyladenosine [no description available] | 2.03 | 1 | 0 | purine nucleoside | |
| tetrahydrodeoxycorticosterone tetrahydrodeoxycorticosterone: RN given refers to (3alpha,5beta)-isomer | 2.44 | 2 | 0 | 21-hydroxy steroid | |
| n-methyladenosine N-methyladenosine: is a inhibitor of cell differentiation. N(6)-methyladenosine : A methyladenosine compound with one methyl group attached to N(6) of the adenine nucleobase. | 2.03 | 1 | 0 | methyladenosine | |
| mizoribine [no description available] | 2.03 | 1 | 0 | imidazoles | anticoronaviral agent |
| 1-amino-1,3-dicarboxycyclopentane 1-amino-1,3-dicarboxycyclopentane: RN given refers to (cis)-isomer | 2.03 | 1 | 0 | ||
| u 73122 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione: structure given in first source. U-73122 : An aza-steroid that is 3-O-methyl-17beta-estradiol in which the 17beta-hydroxy group is replaced by a 6-(maleimid-1-yl)hexylamino group. An inibitor of phospholipase C. | 2.03 | 1 | 0 | aromatic ether; aza-steroid; maleimides | EC 3.1.4.11 (phosphoinositide phospholipase C) inhibitor |
| alphaxalone alphaxalone: RN given refers to (3alpha,5alpha)-isomer; structure | 2.03 | 1 | 0 | corticosteroid hormone | |
| s-nitrosoglutathione [no description available] | 2.03 | 1 | 0 | glutathione derivative; nitrosothio compound | bronchodilator agent; nitric oxide donor; platelet aggregation inhibitor; signalling molecule |
| cp-55,940 [no description available] | 2.44 | 2 | 0 | ||
| vanoxerine vanoxerine dihydrochloride : A hydrochloride salt that is obtained by reaction of vanoxerine with two equivalents of hydrogen chloride. Potent, competitive inhibitor of dopamine uptake (Ki = 1 nM for inhibition of striatal dopamine uptake). Has > 100-fold lower affinity for the noradrenalin and 5-HT uptake carriers. Also a potent sigma ligand (IC50 = 48 nM). Centrally active following systemic administration. | 2.44 | 2 | 0 | hydrochloride | dopamine uptake inhibitor |
| 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1h-imidazole 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole: inhibits platelet aggregation & Ca2+ entry into platelets. SKF-96365 free base : An ether that is 2-(1H-imidazol-1-yl)-1-(4-methoxyphenyl)ethanol in which the hydrogen of the hydroxy group has been substituted by a 3-(4-methoxyphenyl)propyl group. | 2.05 | 1 | 0 | ether; imidazoles; monomethoxybenzene | TRP channel blocker |
| methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate: structure given in first source | 2.44 | 2 | 0 | beta-carbolines | |
| u 69593 U 69593: selective ligand for opioid K-receptor. U69593 : A monocarboxylic acid amide obtained by formal condensation between the carboxy group of phenylacetic acid and the secodary amino group of (5R,7S,8S)-N-methyl-7-(pyrrolidin-1-yl)-1-oxaspiro[4.5]decan-8-amine. | 2.44 | 2 | 0 | monocarboxylic acid amide; N-alkylpyrrolidine; organic heterobicyclic compound; oxaspiro compound | anti-inflammatory agent; diuretic; kappa-opioid receptor agonist |
| u 78517f U 78517F: iron-catalyzed lipid peroxidation inhibitor; structure given in first source; RN given is for diHCl | 2.05 | 1 | 0 | ||
| cv 3988 CV 3988: platelet activating factor antagonist; structure given in first source | 2.44 | 2 | 0 | ||
| beta-carboline-3-carboxylic acid methyl ester beta-carboline-3-carboxylic acid methyl ester: structure given in first source | 2.44 | 2 | 0 | beta-carbolines | |
| methoctramine methoctramine: structure given in first source. methoctramine : A tetramine that is N,N'-bis(6-aminohexyl)octane-1,8-diamine where the primary amino groups both carry 2-methoxybenzyl substituents.. methoctramine tetrahydrochloride : A hydrochloride obtained by combining methoctramine with four molar equivalents of hydrochloric acid. | 2.44 | 2 | 0 | hydrochloride | muscarinic antagonist |
| hypotaurine [no description available] | 2.03 | 1 | 0 | aminosulfinic acid; zwitterion | human metabolite; metabolite; mouse metabolite |
| dihydrokainate [no description available] | 2.03 | 1 | 0 | dicarboxylic acid | |
| gabazine [no description available] | 2.03 | 1 | 0 | ||
| cl 218872 CL 218872: shows specific action on benzodiazepine receptors; structure | 2.03 | 1 | 0 | pyridazines; ring assembly | |
| betaxolol hydrochloride betaxolol hydrochloride : The hydrochloride salt of betaxolol. | 2.44 | 2 | 0 | hydrochloride | antihypertensive agent; beta-adrenergic antagonist |
| catechin (+)-catechin monohydrate : The monohydrate of (+)-catechin. | 2.03 | 1 | 0 | hydrate | geroprotector |
| 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine NAN 190 hydrobromide : A hydrobromide obtained by reaction of NAN 190 with one equivalent of hydrobromic acid. | 2.44 | 2 | 0 | hydrobromide | serotonergic antagonist |
| s-methylthiocitrulline S-methylthiocitrulline: a nitric oxide synthase inhibitor; structure in first source. S-methyl-L-thiocitrulline : An L-arginine derivative in which the guanidino NH2 group of L-arginine is replaced by a methylsufanyl group. | 2.03 | 1 | 0 | imidothiocarbamic ester; L-arginine derivative; L-ornithine derivative; non-proteinogenic L-alpha-amino acid | EC 1.14.13.39 (nitric oxide synthase) inhibitor; neuroprotective agent |
| dihydrocapsaicin [no description available] | 2.03 | 1 | 0 | capsaicinoid | |
| ml 9 [no description available] | 2.03 | 1 | 0 | ||
| parthenolide [no description available] | 2.44 | 2 | 0 | germacranolide | |
| 3',4'-dichlorobenzamil 3',4'-dichlorobenzamil: inhibits Na-Ca exchange in membrane vesicle & papillary muscle preparations from guinea pig heart | 2.44 | 2 | 0 | guanidines; pyrazines | |
| 1-(carboxymethylthio)tetradecane 1-(carboxymethylthio)tetradecane: structure given in first source; alkylthio acetic acid, non-beta-oxidizable | 2.03 | 1 | 0 | straight-chain fatty acid | |
| 2-iodomelatonin [no description available] | 2.03 | 1 | 0 | acetamides | |
| arcaine, sulfate [no description available] | 2.03 | 1 | 0 | ||
| gr 113808 GR 113808: structure given in first source; a 5-HT(4) receptor antagonist: GR 125487 is the HCl salt. GR 113808 : An indolyl carboxylate ester obtained by formal condensation between the carboxy group of 1-methylindole-3-carboxylic acid with the hydroxy group of N-{2-[4-(hydroxymethyl)piperidin-1-yl]ethyl}methanesulfonamide. | 2.44 | 2 | 0 | indolyl carboxylate ester; piperidines; sulfonamide | serotonergic antagonist |
| gallopamil hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| gamma-glutamylaminomethylsulfonic acid [no description available] | 2.03 | 1 | 0 | ||
| buthionine sulfoximine L-buthionine-(S,R)-sulfoximine : A 2-amino-4-(S-butylsulfonimidoyl)butanoic acid which has S-configuration. It is a inhibitor of gamma-glutamylcysteine synthetase and glutathione (GSH) biosynthesis and is capable of enhancing the apoptotic effects of several chemotherapeutic agents. | 2.44 | 2 | 0 | 2-amino-4-(S-butylsulfonimidoyl)butanoic acid | EC 6.3.2.2 (glutamate--cysteine ligase) inhibitor; ferroptosis inducer |
| pramipexole Pramipexole: A benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of PARKINSON DISEASE and RESTLESS LEGS SYNDROME.. pramipexole : A member of the class of benzothiazoles that is 4,5,6,7-tetrahydro-1,3-benzothiazole in which the hydrogens at the 2 and 6-pro-S-positions are substituted by amino and propylamino groups, respectively. | 2.13 | 1 | 0 | benzothiazoles; diamine | antidyskinesia agent; antiparkinson drug; dopamine agonist; radical scavenger |
| sb 204070a SB 204070A: structure given in first source; a selective 5-HT(4) receptor antagonist | 2.44 | 2 | 0 | ||
| 1-(2-(4-aminophenyl)ethyl)-4-(3-trifluoromethylphenyl)piperazine LY 165163: structure given in first source; a serotonin agonist. LY-165163 : A N-arylpiperazine that is piperazine substituted by 2-(4-aminophenyl)ethyl and 3-(trifluoromethyl)phenyl groups at positions 1 and 4, respectively. It is a selective 5-HT1A serotonin receptor agonist and 5-HT1D serotonin receptor antagonist. | 2.44 | 2 | 0 | (trifluoromethyl)benzenes; N-alkylpiperazine; N-arylpiperazine; primary arylamine; substituted aniline | geroprotector; serotonergic agonist |
| l 655240 L 655240: thromboxane and prostaglandin endoperoxide receptor antagonist; structure given in first source; RN given is for parent cpd | 2.03 | 1 | 0 | methylindole | |
| san 58035 [no description available] | 2.44 | 2 | 0 | ||
| mk 912 [no description available] | 2.05 | 1 | 0 | ||
| nnc 711 NNC 711: structure in first source | 2.03 | 1 | 0 | ||
| 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-n,n-diethylbenzamide 4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide: a highly-selective, nonpeptide delta opioid receptor agonist; structure given in first source | 2.44 | 2 | 0 | diarylmethane | |
| sk&f 86466 benalfocin: RN & RR given from first source; RN not in Chemline 9/28/83; structure given in first source | 2.05 | 1 | 0 | benzazepine | |
| e 64 E 64: cysteine protease inhibitor of microbial origin, which inhibits cathepsin B (EC 3.4.22.1) and cathepsin L (EC 3.4.22.-) | 2.44 | 2 | 0 | dicarboxylic acid monoamide; epoxy monocarboxylic acid; guanidines; L-leucine derivative; zwitterion | antimalarial; antiparasitic agent; protease inhibitor |
| azetidine-2,4-dicarboxylic acid azetidine-2,4-dicarboxylic acid: activates neuronal metabotropic receptors; RN given refers to (trans-isomer); RN for cpd without isomeric designation not avail 10/93 | 2.03 | 1 | 0 | ||
| w 7 [no description available] | 2.05 | 1 | 0 | ||
| pre 084 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate: structure given in first source | 2.44 | 2 | 0 | morpholines | |
| methotrexate [no description available] | 2.44 | 2 | 0 | dicarboxylic acid; monocarboxylic acid amide; pteridines | abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent |
| 1-(2-allylphenoxy)-3-((8-bromoacetylamino-4-menthane-1-yl)amino)-1-propanol 1-(2-allylphenoxy)-3-((8-bromoacetylamino-4-menthane-1-yl)amino)-1-propanol: irreversibly inactivates the dihydroalprenolol binding site; alprenolol analog; isopropylamino group of alprenolol replaced by 8-bromoacetylamino-1-amino-p-menthane moiety in the 1 position; structure given in first source | 2.44 | 2 | 0 | ||
| sr 2640 SR 2640: leukotriene D4 and E4 antagonist | 2.44 | 2 | 0 | quinolines | |
| ici 204448 [no description available] | 2.03 | 1 | 0 | ||
| 4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride 4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride: has high affinity and selectivity for 5-HT3 receptors; structure given in first source | 2.03 | 1 | 0 | ||
| n,n-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide: binds with high affinity to glial mitochondrial diazepam binding inhibitor receptors & increases mitochondrial steroidogenesis | 2.44 | 2 | 0 | phenylindole | |
| 4-(benzodioxan-5-yl)-1-(indan-2-yl)piperazine [no description available] | 2.05 | 1 | 0 | ||
| 3,5-bis(trifluoromethyl)benzyl n-acetyltryptophan 3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan: structure given in first source; substance P and neurokinin receptor antagonist | 2.03 | 1 | 0 | ||
| 8-cyclopentyl-3-(3-((4-(fluorosulfonyl)benzoyl)oxy)propyl)-1-propylxanthine 8-cyclopentyl-3-(3-((4-(fluorosulfonyl)benzoyl)oxy)propyl)-1-propylxanthine: structure given in first source | 2.44 | 2 | 0 | ||
| l 741626 3-(4-(4-chlorophenyl-4-hydroxypiperidino)methyl)indole: structure in first source | 2.44 | 2 | 0 | piperidines | |
| nisoxetine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| ng-nitroarginine methyl ester N(gamma)-nitro-L-arginine methyl ester hydrochloride : A hydrochloride obtained by combining N(gamma)-nitro-L-arginine methyl ester with one equivalent of hydrochloric acid. | 2.03 | 1 | 0 | hydrochloride | EC 1.14.13.39 (nitric oxide synthase) inhibitor |
| tilarginine acetate [no description available] | 2.03 | 1 | 0 | ||
| alpha-guanidinoglutaric acid alpha-guanidinoglutaric acid: identified in the convulsive period of cobalt-induced seizures from cat cerebral cortex; RN given for cpd with unspecified guanidino-locant | 2.03 | 1 | 0 | L-glutamic acid derivative | |
| 3,4-dichloro-n-methyl-n-(2-(1-pyrrolidinyl)cyclohexyl)-benzeneacetamide, (trans)-(+-)-isomer [no description available] | 2.44 | 2 | 0 | ||
| imidazole-4-acetic acid hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| nsc-141549 [no description available] | 2.44 | 2 | 0 | ||
| 2-chloro-2-deoxyglucose [no description available] | 2.03 | 1 | 0 | ||
| idazoxan hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| isoguvacine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| 8-methoxymethyl-3-isobutyl-1-methylxanthine 8-methoxymethyl-3-isobutyl-1-methylxanthine: inhibitor of phosphodiesterase I | 2.03 | 1 | 0 | oxopurine | |
| cyc 202 seliciclib : 2,6-Diaminopurine carrying benzylamino, (2R)-1-hydroxybutan-2-yl and isopropyl substituents at C-6, C-2-N and N-9 respectively. It is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors. | 2.44 | 2 | 0 | 2,6-diaminopurines | antiviral drug; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor |
| Serotonin hydrochloride [no description available] | 2.03 | 1 | 0 | tryptamines | |
| n-phthaloylglutamic acid N-phthaloyl-L-glutamic acid : A glutamic acid derivative that is L-glutamic acid in which the two hydrogens on the amino group are substituted by a phthaloyl group. | 2.03 | 1 | 0 | L-glutamic acid derivative; phthalimides | |
| 1,3-dipropyl-7-methylxanthine 1,3-dipropyl-7-methylxanthine: structure given in first source | 2.03 | 1 | 0 | ||
| ag 3-5 icilin: a cooling compound that activates TRPM8 | 2.03 | 1 | 0 | C-nitro compound | |
| n-n-propylnorapomorphine [no description available] | 2.03 | 1 | 0 | aporphine alkaloid | |
| urapidil monohydrochloride [no description available] | 2.44 | 2 | 0 | ||
| aminopterin Aminopterin: A folic acid derivative used as a rodenticide that has been shown to be teratogenic. | 2.44 | 2 | 0 | dicarboxylic acid | EC 1.5.1.3 (dihydrofolate reductase) inhibitor; mutagen |
| azepexole, dihydrochloride [no description available] | 2.03 | 1 | 0 | ||
| 2,5-dimethoxy-4-iodoamphetamine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| abt 980 [no description available] | 2.44 | 2 | 0 | ||
| sk&f 75670 SK&F 75670: RN refers to HBr; N-methyl derivative of SK&F 38393 | 2.44 | 2 | 0 | ||
| esatenolol esatenolol : The (S)-enantiomer of atenolol. | 2.03 | 1 | 0 | atenolol | beta-adrenergic antagonist |
| nbi 27914 [no description available] | 2.44 | 2 | 0 | dialkylarylamine; tertiary amino compound | |
| sb 216763 [no description available] | 2.44 | 2 | 0 | indoles; maleimides | |
| dizocilpine [no description available] | 2.05 | 1 | 0 | secondary amino compound; tetracyclic antidepressant | anaesthetic; anticonvulsant; neuroprotective agent; nicotinic antagonist; NMDA receptor antagonist |
| (R)-atenolol (R)-atenolol : The (R)-enantiomer of atenolol. | 2.03 | 1 | 0 | atenolol | |
| memantine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | antidepressant; antiparkinson drug; dopaminergic agent; neuroprotective agent; NMDA receptor antagonist |
| sibenadet sibenadet: structure in first source | 2.77 | 3 | 0 | ||
| pefabloc [no description available] | 2.03 | 1 | 0 | ||
| pongidae [no description available] | 2.44 | 2 | 0 | ||
| succinylproline [no description available] | 2.03 | 1 | 0 | N-acyl-amino acid | |
| sb 205384 SB 205384: structure in first source | 2.44 | 2 | 0 | thienopyridine | |
| hydrastine [no description available] | 2.44 | 2 | 0 | isoquinolines | metabolite |
| gabaculine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| etiron monohydrobromide [no description available] | 2.03 | 1 | 0 | ||
| bmy 7378 [no description available] | 2.03 | 1 | 0 | ||
| vesamicol [no description available] | 2.03 | 1 | 0 | ||
| cortisone [no description available] | 2.03 | 1 | 0 | 11-oxo steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(4) steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | human metabolite; mouse metabolite |
| vincristine sulfate [no description available] | 2.44 | 2 | 0 | organic sulfate salt | antineoplastic agent; geroprotector |
| n-methylserotonin oxalate salt [no description available] | 2.03 | 1 | 0 | ||
| nsc 95397 [no description available] | 2.44 | 2 | 0 | 1,4-naphthoquinones | |
| wortmannin [no description available] | 2.44 | 2 | 0 | acetate ester; cyclic ketone; delta-lactone; organic heteropentacyclic compound | anticoronaviral agent; antineoplastic agent; autophagy inhibitor; EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor; geroprotector; Penicillium metabolite; radiosensitizing agent |
| lithium chloride Lithium Chloride: A salt of lithium that has been used experimentally as an immunomodulator.. lithium chloride : A metal chloride salt with a Li(+) counterion. | 2.03 | 1 | 0 | inorganic chloride; lithium salt | antimanic drug; geroprotector |
| canavanine L-canavanine : A non-proteinogenic L-alpha-amino acid that is L-homoserine substituted at oxygen with a guanidino (carbamimidamido) group. Although structurally related to L-arginine, it is non-proteinogenic. | 2.03 | 1 | 0 | amino acid zwitterion; non-proteinogenic L-alpha-amino acid | phytogenic insecticide; plant metabolite |
| 5-hydroxytryptophan hydroxytryptophan : A hydroxy-amino acid that is tryptophan substituted by at least one hydroxy group at unspecified position.. 5-hydroxy-L-tryptophan : The L-enantiomer of 5-hydroxytryptophan. | 2.03 | 1 | 0 | 5-hydroxytryptophan; amino acid zwitterion; hydroxy-L-tryptophan; non-proteinogenic L-alpha-amino acid | human metabolite; mouse metabolite; plant metabolite |
| ouabain Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.. cardiac glycoside : Steroid lactones containing sugar residues that act on the contractile force of the cardiac muscles.. ouabain : A steroid hormone that is a multi-hydroxylated alpha-L-rhamnosyl cardenoloide. It binds to and inhibits the plasma membrane Na(+)/K(+)-ATPase (sodium pump). It has been isolated naturally from Strophanthus gratus. | 2.44 | 2 | 0 | 11alpha-hydroxy steroid; 14beta-hydroxy steroid; 5beta-hydroxy steroid; alpha-L-rhamnoside; cardenolide glycoside; steroid hormone | anti-arrhythmia drug; cardiotonic drug; EC 2.3.3.1 [citrate (Si)-synthase] inhibitor; EC 3.1.3.41 (4-nitrophenylphosphatase) inhibitor; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor; ion transport inhibitor; plant metabolite |
| tosylphenylalanyl chloromethyl ketone Tosylphenylalanyl Chloromethyl Ketone: An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.. N-tosyl-L-phenylalanyl chloromethyl ketone : The N-tosyl derivative of L-phenylalanyl chloromethyl ketone. | 2.03 | 1 | 0 | alpha-chloroketone; sulfonamide | alkylating agent; serine proteinase inhibitor |
| monoiodotyrosine Monoiodotyrosine: A product from the iodination of tyrosine. In the biosynthesis of thyroid hormones (THYROXINE and TRIIODOTHYRONINE), tyrosine is first iodized to monoiodotyrosine.. iodotyrosine : A tyrosine derivative which has at least one iodo-substituent on the benzyl moiety.. monoiodotyrosine : An iodotyrosine carrying a single iodo substituent.. 3-iodo-L-tyrosine : The monoiodotyrosine that is L-tyrosine carrying an iodo-substituent at position C-3 of the benzyl group. | 2.03 | 1 | 0 | amino acid zwitterion; L-tyrosine derivative; monoiodotyrosine; non-proteinogenic L-alpha-amino acid | EC 1.14.16.2 (tyrosine 3-monooxygenase) inhibitor; human metabolite; mouse metabolite |
| nitroarginine Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6). N(gamma)-nitro-L-arginine : An L-arginine derivative that is L-arginine in which the terminal nitrogen of the guanidyl group is replaced by a nitro group. | 2.03 | 1 | 0 | guanidines; L-arginine derivative; N-nitro compound; non-proteinogenic L-alpha-amino acid | |
| willardiine willardiine: isolated from seeds of Acacia willariana; structure. 3-(uracil-1-yl)-L-alanine : The 3-(uracil-1-yl) derivative of L-alanine. | 2.03 | 1 | 0 | amino acid zwitterion; L-alanine derivative; non-proteinogenic L-alpha-amino acid | |
| cortodoxone Cortodoxone: 17,21-Dihydroxypregn-4-ene-3,20-dione. A 17-hydroxycorticosteroid with glucocorticoid and anti-inflammatory activities.. 11-deoxycortisol : A deoxycortisol that is cortisol in which the hydroxy group at position 11 has been replaced by a hydrogen. | 2.44 | 2 | 0 | deoxycortisol; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | human metabolite; mouse metabolite |
| amiodarone hydrochloride [no description available] | 2.44 | 2 | 0 | aromatic ketone | |
| dicyclomine hydrochloride dicyclomine hydrochloride : The hydrochloride salt of dicyclomine. An anticholinergic, it is used to treat or prevent spasm in the muscles of the gastrointestinal tract, particularly that associated with irritable bowel syndrome. | 2.44 | 2 | 0 | hydrochloride | antispasmodic drug; muscarinic antagonist |
| metyrosine alpha-methyl-L-tyrosine : An L-tyrosine derivative that consists of L-tyrosine bearing an additional methyl substituent at position 2. An inhibitor of the enzyme tyrosine 3-monooxygenase, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with pheochromocytoma. | 2.03 | 1 | 0 | L-tyrosine derivative; non-proteinogenic L-alpha-amino acid | antihypertensive agent; EC 1.14.16.2 (tyrosine 3-monooxygenase) inhibitor |
| nortriptyline hydrochloride [no description available] | 2.44 | 2 | 0 | organic tricyclic compound | geroprotector |
| paromomycin sulfate paromomycin sulfate : An aminoglycoside sulfate salt resulting from the treatment of paromomycin with sulfuric acid. A broad-spectrum antibiotic, it is used for the treatment of acute and chronic intestinal protozoal infections, but is not effective for extraintestinal protozoal infections. It is also used as a therapeutic against visceral leishmaniasis. | 2.03 | 1 | 0 | ||
| Dubinidine [no description available] | 2.03 | 1 | 0 | organic heterotricyclic compound; organonitrogen heterocyclic compound; oxacycle | |
| cyclopamine [no description available] | 2.03 | 1 | 0 | piperidines | glioma-associated oncogene inhibitor |
| s-(4-azidophenacyl)glutathione S-(4-azidophenacyl)glutathione: photoaffinity label deriv of glutathione; inhibits glyoxalase I (EC 4.4.1.5) | 2.03 | 1 | 0 | peptide | |
| hydroxylamine hydrochloride [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| sb 228357 SB 228357: a neuroleptic with equivalent or higher antagonist affinity for 5-HT2 than for dopamine D2 receptor | 2.44 | 2 | 0 | indolyl carboxylic acid | |
| 3,5-dihydroxyphenylglycine (S)-3,5-dihydroxyphenylglycine : A glycine derivative that is L-alpha-phenylglycine substituted at positions 3 and 5 on the phenyl ring by hydroxy groups. | 2.03 | 1 | 0 | amino acid zwitterion; non-proteinogenic L-alpha-amino acid; resorcinols | |
| actinonin actinonin: natural hydroxamic acid, pseudopeptide antibiotic isolated from Streptomyces species; structure | 2.44 | 2 | 0 | ||
| vinpocetine vinpocetine: whole issue of Arzneim Forsch (23 articles) discuss this drug; Arzneim Forsch 26(10a);1976; RN given refers to parent cpd with unspecified isomeric designation | 2.44 | 2 | 0 | alkaloid | geroprotector |
| darifenacin darifenacin : 2-[(3S)-1-Ethylpyrrolidin-3-yl]-2,2-diphenylacetamide in which one of the hydrogens at the 2-position of the ethyl group is substituted by a 2,3-dihydro-1-benzofuran-5-yl group. It is a selective antagonist for the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions, and is used as the hydrobromide salt in the management of urinary incontinence. | 2.47 | 2 | 0 | 1-benzofurans; monocarboxylic acid amide; pyrrolidines | antispasmodic drug; muscarinic antagonist |
| dihydroergocristine monomesylate dihydroergocristine mesylate : The methanesulfonic acid salt of dihydroergocristine. It has been used as the for the symptomatic treatment of mental deterioration associated with cerebrovascular insufficiency and in peripheral vascular disease. It is also a component of ergoloid mesylate (codergocrine mesilate), a mixture of ergot alkaloid derivatives that is used as a vasodilator and has shown mild benefits in the treatment of vascular dementia. | 2.44 | 2 | 0 | methanesulfonate salt | alpha-adrenergic antagonist; geroprotector; vasodilator agent |
| tretinoin Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).. retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).. all-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry. | 2.44 | 2 | 0 | retinoic acid; vitamin A | anti-inflammatory agent; antineoplastic agent; antioxidant; AP-1 antagonist; human metabolite; keratolytic drug; retinoic acid receptor agonist; retinoid X receptor agonist; signalling molecule |
| resveratrol trans-resveratrol : A resveratrol in which the double bond has E configuration. | 2.44 | 2 | 0 | resveratrol | antioxidant; phytoalexin; plant metabolite; quorum sensing inhibitor; radical scavenger |
| oleic acid Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed). oleic acid : An octadec-9-enoic acid in which the double bond at C-9 has Z (cis) stereochemistry. | 2.03 | 1 | 0 | octadec-9-enoic acid | antioxidant; Daphnia galeata metabolite; EC 3.1.1.1 (carboxylesterase) inhibitor; Escherichia coli metabolite; mouse metabolite; plant metabolite; solvent |
| thapsigargin Thapsigargin: A sesquiterpene lactone found in roots of THAPSIA. It inhibits SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES.. thapsigargin : An organic heterotricyclic compound that is a hexa-oxygenated 6,7-guaianolide isolated fron the roots of Thapsia garganica L., Apiaceae. A potent skin irritant, it is used in traditional medicine as a counter-irritant. Thapsigargin inhibits Ca(2+)-transporting ATPase mediated uptake of calcium ions into sarcoplasmic reticulum and is used in experimentation examining the impacts of increasing cytosolic calcium concentrations. | 2.44 | 2 | 0 | butyrate ester; organic heterotricyclic compound; sesquiterpene lactone | calcium channel blocker; EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor |
| brivudine brivudine: anti-herpes agent | 2.03 | 1 | 0 | ||
| 5,11-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol 5,11-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol: estrogen receptor ligand; structure in first source. (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol : A carbotetracyclic compound that is 5,6,11,12-tetrahydrochrysene substituted by hydroxy groups at positions 2 and 8 and by ethyl groups at positions 5 and 11 (the 5R,11R-stereoisomer). It is an agonist of ER-alpha and antagonist of ER-beta receptors. | 2.44 | 2 | 0 | carbotetracyclic compound; polyphenol | estrogen receptor agonist; estrogen receptor antagonist; geroprotector; neuroprotective agent |
| 2-amino-3-(5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl)propionic acid 2-amino-3-(5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl)propionic acid: structure in first source | 2.03 | 1 | 0 | ||
| adenosine-5'-(n-ethylcarboxamide) Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.. N-ethyl-5'-carboxamidoadenosine : A derivative of adenosine in which the 5'-hydroxymethyl group is replaced by an N-ethylcarboxamido group. | 2.03 | 1 | 0 | adenosines; monocarboxylic acid amide | adenosine A1 receptor agonist; adenosine A2A receptor agonist; antineoplastic agent; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; vasodilator agent |
| 6-bromoindirubin-3'-oxime 6-bromoindirubin-3'-oxime: structure in first source. 6-bromoindirubin-3'-oxime : A member of the class of biindoles that is indirubin substituted at position 6 by a bromo group and in which the keto group at position 3' has undergone condensation with hydroxylamine to form the corresponding oxime. | 2.05 | 1 | 0 | ||
| L-cycloserine L-cycloserine : A 4-amino-1,2-oxazolidin-3-one that has S configuration. An antibiotic isolated from Erwinia uredovora. | 2.03 | 1 | 0 | 4-amino-1,2-oxazolidin-3-one | anti-HIV agent; anticonvulsant; EC 2.3.1.50 (serine C-palmitoyltransferase) inhibitor |
| h 89 N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide: structure given in first source. N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide : A member of the class of isoquinolines that is the sulfonamide obtained by formal condensation of the sulfo group of isoquinoline-5-sulfonic acid with the primary amino group of N(1)-[3-(4-bromophenyl)prop-2-en-1-yl]ethane-1,2-diamine. It is a protein kinase A inhibitor.. (E)-N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide : A N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide in which the double bond adopts a trans-configuration. | 2.05 | 1 | 0 | N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide | |
| 1,4-dideoxy-1,4-imino-d-arabinitol [no description available] | 2.03 | 1 | 0 | ||
| purvalanol a 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine: purvalanol A is the (1R)-isomer; | 2.03 | 1 | 0 | purvalanol | |
| melphalan Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.. melphalan : A phenylalanine derivative comprising L-phenylalanine having [bis(2-chloroethyl)amino group at the 4-position on the phenyl ring. | 2.44 | 2 | 0 | L-phenylalanine derivative; nitrogen mustard; non-proteinogenic L-alpha-amino acid; organochlorine compound | alkylating agent; antineoplastic agent; carcinogenic agent; drug allergen; immunosuppressive agent |
| isoliquiritigenin [no description available] | 2.44 | 2 | 0 | chalcones | antineoplastic agent; biological pigment; EC 1.14.18.1 (tyrosinase) inhibitor; GABA modulator; geroprotector; metabolite; NMDA receptor antagonist |
| rauwolscine Rauwolscine: A stereoisomer of yohimbine. | 2.03 | 1 | 0 | methyl 17-hydroxy-20xi-yohimban-16-carboxylate | |
| gw9662 2-chloro-5-nitrobenzanilide: pretreatment of peroxisome proliferator activated receptors with GW9662 results in the irreversible loss of ligand binding | 2.44 | 2 | 0 | benzamides | |
| calmidazolium calmidazolium chloride : The organic choride salt of calmidazolium. | 2.44 | 2 | 0 | organic chloride salt | apoptosis inducer; calmodulin antagonist |
| tropisetron hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| Reactive blue 2 [no description available] | 2.03 | 1 | 0 | anthraquinone | |
| 5,6-dichloro-1-ethyl-1,3-dihydro-2h-benzimidazol-2-one 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one: stimulates Cl- secretion in the mouse jejunum | 2.03 | 1 | 0 | dichlorobenzene | |
| quinidine sulfate [no description available] | 2.44 | 2 | 0 | ||
| ipratropium bromide anhydrous [no description available] | 2.03 | 1 | 0 | ||
| methamilane methiodide [no description available] | 2.03 | 1 | 0 | ||
| pilocarpine nitrate [no description available] | 2.03 | 1 | 0 | ||
| r 59949 R 59949: diacylglycerol kinase inhibitor | 2.44 | 2 | 0 | diarylmethane | |
| n(6)-cyclopentyladenosine [no description available] | 2.44 | 2 | 0 | ||
| methylatropine nitrate [no description available] | 2.03 | 1 | 0 | ||
| sb 366791 N-(3-methoxyphenyl)-4-chlorocinnamanilide: a TRPV1 antagonist; structure in first source | 2.44 | 2 | 0 | ||
| ag-213 tyrphostin 47: inhibits protein-tyrosine kinase activity of EGF-R both in vitro and in living cells; | 2.44 | 2 | 0 | ||
| 3,3',4,5'-tetrahydroxystilbene 3,3',4,5'-tetrahydroxystilbene: demethyl derivative of isorhapontigenin; structure in first source; a Syk kinase inhibitor; found in heartwood of FABACEAE; inhibitor of photosynthesis in spinach chloroplasts; may be inhibitor of plant growth; RN given refers to (E)-isomer. piceatannol : A stilbenol that is trans-stilbene in which one of the phenyl groups is substituted by hydroxy groups at positions 3 and 4, while the other phenyl group is substituted by hydroxy groups at positions 3 and 5. | 2.44 | 2 | 0 | catechols; polyphenol; resorcinols; stilbenol | antineoplastic agent; apoptosis inducer; geroprotector; hypoglycemic agent; plant metabolite; protein kinase inhibitor; tyrosine kinase inhibitor |
| bemesetron [no description available] | 2.44 | 2 | 0 | ||
| (S)-(-)-pindolol [no description available] | 2.03 | 1 | 0 | pindolol | |
| levosulpiride (S)-(-)-sulpiride : An optically active form of sulpiride having (S)-configuration. The active enantiomer of the racemic drug sulpiride. Selective D2-like dopamine antagonist (Ki values are ~ 0.015. ~ 0.013, 1, ~ 45 and ~ 77 muM at D2, D3, D4, D1 and D5 receptors respectively). | 2.03 | 1 | 0 | sulpiride | antidepressant; antiemetic; antipsychotic agent; dopaminergic antagonist |
| ritodrine (1S,2R)-ritodrine : A 4-[2-[[1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]phenol that has (1S,2R)-configuration. | 2.08 | 1 | 0 | 4-[2-[[1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]phenol | |
| caffeic acid trans-caffeic acid : The trans-isomer of caffeic acid. | 2.03 | 1 | 0 | caffeic acid | geroprotector; mouse metabolite |
| 4-fluorophenyl-L-alanine 4-fluorophenyl-L-alanine : A L-phenylalanine derivative that is L-phenylalanine in which the hydrogen at position 4 on the benzene ring is replaced by a fluoro group. | 2.44 | 2 | 0 | 4-fluorophenylalanine; L-phenylalanine derivative; non-proteinogenic L-alpha-amino acid | |
| phenylthiazolylthiourea Phenylthiazolylthiourea: A dopamine-beta-hydroxylase inhibitor. | 2.05 | 1 | 0 | ||
| urocanic acid Urocanic Acid: 4-Imidazoleacrylic acid.. urocanic acid : An alpha,beta-unsaturated monocarboxylic acid that is prop-2-enoic acid substituted by a 1H-imidazol-4-yl group at position 3. It is a metabolite of hidtidine.. trans-urocanic acid : A urocanic acid in which the double bond of the carboxyethene moiety has E configuration. | 2.03 | 1 | 0 | urocanic acid | human metabolite |
| (2'-(4-aminophenyl)-(2,5'-bi-1h-benzimidazol)-5-amine) [no description available] | 2.05 | 1 | 0 | benzimidazoles | |
| cotinine Cotinine: The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.. (-)-cotinine : An N-alkylpyrrolidine that consists of N-methylpyrrolidinone bearing a pyridin-3-yl substituent at position C-5 (the 5S-enantiomer). It is an alkaloid commonly found in Nicotiana tabacum. | 2.44 | 2 | 0 | N-alkylpyrrolidine; pyridines; pyrrolidin-2-ones; pyrrolidine alkaloid | antidepressant; biomarker; human xenobiotic metabolite; plant metabolite |
| cinnarizine Cinnarizine: A piperazine derivative having histamine H1-receptor and calcium-channel blocking activity with vasodilating and antiemetic properties but it induces PARKINSONIAN DISORDERS. | 2.44 | 2 | 0 | diarylmethane; N-alkylpiperazine; olefinic compound | anti-allergic agent; antiemetic; calcium channel blocker; geroprotector; H1-receptor antagonist; histamine antagonist; muscarinic antagonist |
| sulindac Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.. sulindac : A monocarboxylic acid that is 1-benzylidene-1H-indene which is substituted at positions 2, 3, and 5 by methyl, carboxymethyl, and fluorine respectively, and in which the phenyl group of the benzylidene moiety is substituted at the para position by a methylsulfinyl group. It is a prodrug for the corresponding sulfide, a non-steroidal anti-inflammatory drug, used particularly in the treatment of acute and chronic inflammatory conditions. | 2.03 | 1 | 0 | monocarboxylic acid; organofluorine compound; sulfoxide | analgesic; antineoplastic agent; antipyretic; apoptosis inducer; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug; prodrug; tocolytic agent |
| cysteine sulfinic acid 3-sulfino-L-alanine : The organosulfinic acid arising from oxidation of the sulfhydryl group of L-cysteine. | 2.03 | 1 | 0 | organosulfinic acid; S-substituted L-cysteine | Escherichia coli metabolite; human metabolite; metabotropic glutamate receptor agonist; mouse metabolite |
| d-ap7 [no description available] | 2.03 | 1 | 0 | ||
| tg 003 TG 003: a Clk inhibitor; structure in first source | 2.05 | 1 | 0 | ||
| (1R,2S)-tranylcypromine hydrochloride (1R,2S)-tranylcypromine hydrochloride : A hydrochloride obtained by combining (1R,2S)-tranylcypromine with one equivalent of hydrochloric acid. | 2.44 | 2 | 0 | hydrochloride | |
| tacrine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| 4-bromotetramisole, oxalate (1:1), salt(s)-isomer [no description available] | 2.44 | 2 | 0 | ||
| 3-hydroxybenzylhydrazine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| 1-(3-chlorophenyl)biguanide hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| 4-chlorophenylalanine methyl ester, hydrochloride, (dl)-isomer [no description available] | 2.03 | 1 | 0 | ||
| capsazepine capsazepine: modified capsaicin molecule; a capsaicin receptor antagonist. capsazepine : A benzazepine that is 2,3,4,5-tetrahydro-1H-2-benzazepine which is substituted by hydroxy groups at positions 7 and 8 and on the nitrogen atom by a 2-(p-chlorophenyl)ethylaminothiocarbonyl group. A synthetic analogue of capsaicin, it was the first reported capsaicin receptor antagonist. | 2.44 | 2 | 0 | benzazepine; catechols; monochlorobenzenes; thioureas | capsaicin receptor antagonist |
| diphenyleneiodium chloride dibenziodolium chloride : An organic chloride salt having dibenziodolium as the counterion. | 2.44 | 2 | 0 | organic chloride salt | EC 1.6.3.1. [NAD(P)H oxidase (H2O2-forming)] inhibitor; G-protein-coupled receptor agonist |
| azetidine-2,4-dicarboxylic acid, (cis)-isomer [no description available] | 2.03 | 1 | 0 | ||
| tamoxifen citrate [no description available] | 2.44 | 2 | 0 | citrate salt | angiogenesis inhibitor; anticoronaviral agent |
| pimagedine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| Betaine Aldehyde Chloride [no description available] | 2.03 | 1 | 0 | quaternary ammonium salt | |
| eskazine [no description available] | 2.44 | 2 | 0 | ||
| 3-(n,n-dimethylsulfonamido)-4-methyl-nitrobenzene BRL-50481 : A C-nitro compound that is benzene substituted by N,N-dimethylaminosulfonyl, methyl and nitro groups at positions 1, 2 and 5, respectively. It is a phosphodiesterase inhibitor selective for the PDE7 subtype (Ki = 180 nM). | 2.05 | 1 | 0 | C-nitro compound; sulfonamide; toluenes | bone density conservation agent; EC 3.1.4.53 (3',5'-cyclic-AMP phosphodiesterase) inhibitor; geroprotector |
| monastrol monastrol: stops mitosis by fostering formation of monopolar spindles; structure in first source. (S)-monastrol : An ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate that has S configuration.. monastrol : A racemate comprising equimolar amounts of R- and S-monastrol.. ethyl 4-(3-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate : A member of the class of thioureas that is 3,4-dihydropyrimidine-2(1)-thione substituted by a 3-hydroxyphenyl group at position 4, an ethoxycarbonyl group at position 5, and a methyl group at position 6. | 2.03 | 1 | 0 | enoate ester; ethyl ester; phenols; racemate; thioureas | antileishmanial agent; antimitotic; antineoplastic agent; EC 3.5.1.5 (urease) inhibitor |
| u 0126 U 0126: protein kinase kinase inhibitor; structure in first source | 2.44 | 2 | 0 | aryl sulfide; dinitrile; enamine; substituted aniline | antineoplastic agent; antioxidant; apoptosis inducer; EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor; osteogenesis regulator; vasoconstrictor agent |
| 4-diphenylacetoxy-n-methylpiperidine methiodide 4-DAMP methiodide : A quaternary ammonium salt obtained by combining equimolar amounts of 4-diphenylacetoxy-N-methylpiperidine and iodomethane. | 2.44 | 2 | 0 | iodide salt; quaternary ammonium salt | cholinergic antagonist; muscarinic antagonist |
| quinine [no description available] | 2.05 | 1 | 0 | cinchona alkaloid | antimalarial; muscle relaxant; non-narcotic analgesic |
| 1-(4-hydroxybenzyl)imidazole-2-thiol 1-(4-hydroxybenzyl)imidazole-2-thiol: RN & structure given in first source; RN not in Chemline 3/87 | 2.03 | 1 | 0 | ||
| 2-chloro-n(6)-(3-iodobenzyl)adenosine-5'-n-methyluronamide 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide: structure given in first source | 2.44 | 2 | 0 | ||
| bp 897 BP 897: a dopamine D3 receptor agonist; structure in first source | 2.44 | 2 | 0 | naphthalenecarboxamide | |
| trequinsin hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| neboglamine neboglamine: potential memory enhancer | 2.03 | 1 | 0 | ||
| arformoterol arformoterol : An N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide in which both of the stereocentres have R configuration. The active enantiomer of formoterol, it is administered by inhalation (generally as the tartrate salt) as a direct-acting sympathomimetic and bronchodilator for the treatment of chronic obstructive pulmonary disease (any progressive respiratory disease that makes it harder to breathe over time, such as chronic bronchitis and emphysema). | 2.44 | 2 | 0 | N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide | anti-asthmatic drug; beta-adrenergic agonist; bronchodilator agent |
| benzatropine methanesulfonate benzatropine mesylate : The methanesulfonate salt of benzatropine. An acetylcholine receptor antagonist, it is used in the treatment of Parkinson's disease, and to reduce parkinsonism and akathisia side effects of antipsychotic treatments. | 2.44 | 2 | 0 | ||
| sb 203186 [no description available] | 2.03 | 1 | 0 | indolyl carboxylic acid | |
| n-(1-methyl-5-indolyl)-n'-(3-methyl-5-isothiazolyl)urea N-(1-methyl-5-indolyl)-N'-(3-methyl-5-isothiazolyl)urea: a 5-HT(2B) receptor antagonist; structure given in first source. 1-(1-methylindol-5-yl)-3-(3-methyl-1,2-thiazol-5-yl)urea : A member of ther class of ureas that is urea in which a hydrogen attached to one of the nitrogens has been replaced by an N-methylindol-5-yl group, while a hydrogen attached to the other nitrogen has been replaced by a 3-methyl-1,2-thiazol-5-yl group. It is a potent and selective antagonist for the 5-hydroxytryptamine 2B (5-HT2B) receptor. | 2.44 | 2 | 0 | 1,2-thiazoles; indoles; ureas | receptor modulator; serotonergic antagonist |
| gw 7647 GW 7647: a PPAR-alpha agonist; structure in first source. GW 7647 : A monocarboxylic acid that is 2-(phenylsulfanyl)isobutyric acid in which the phenyl group is substituted at the para- position by a 3-aza-7-cyclohexylhept-1-yl group in which the nitrogen is acylated by a (cyclohexylamino)carbonyl group. | 2.44 | 2 | 0 | aryl sulfide; monocarboxylic acid; ureas | PPARalpha agonist |
| ro 41-0960 [no description available] | 2.44 | 2 | 0 | ||
| cgp 13501 CGP 13501: structure in first source | 2.03 | 1 | 0 | alkylbenzene | |
| n-(2-(4-(4-chlorophenyl)piperazin-1-yl)ethyl)-3-methoxybenzamide N-(2-(4-(4-chlorophenyl)piperazin-1-yl)ethyl)-3-methoxybenzamide: dopamine D4 ligand; structure in first source | 2.44 | 2 | 0 | ||
| l 663536 MK-886: orally active leukotriene biosynthesis inhibitor. 3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(propan-2-yl)-1H-indol-2-yl]-2,2-dimethylpropanoic acid : A member of the class of indoles that is 1H-indole substituted by a isopropyl group at position 5, a tert-butylsulfanediyl group at position 3, a 4-chlorobenzyl group at position 1 and a 2-carboxy-2-methylpropyl group at position 2. It acts as an inhibitor of arachidonate 5-lipoxygenase. | 2.05 | 1 | 0 | aryl sulfide; indoles; monocarboxylic acid; monochlorobenzenes | antineoplastic agent; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor; leukotriene antagonist |
| brl 15572 3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol : An N-alkylpiperazine that is 1-(3-chlorophenyl)piperazine carrying a 3,3-diphenyl-2-hydroxyprop-1-yl group at position 4. A selective h5-HT1D antagonist, displaying 60-fold selectivity over h5-HT1B, and exhibiting little or no affinity for a range of other receptor types. | 2.44 | 2 | 0 | monochlorobenzenes; N-alkylpiperazine; N-arylpiperazine; secondary alcohol | geroprotector; serotonergic antagonist |
| mrs 1523 2,3-diethyl-4,5-dipropyl-6-phenylpyridine-3-thiocarboxylate-5-carboxylate: adenosine A3 receptor antagonist | 2.44 | 2 | 0 | ||
| or486 OR486: structure given in first source | 2.03 | 1 | 0 | ||
| fg 9041 FG 9041: structure given in first source | 2.44 | 2 | 0 | quinoxaline derivative | |
| iik7 IIK7: structure in first source | 2.03 | 1 | 0 | ||
| sb 415286 3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione: a glycogen synthase kinase-3 inhibitor; structure in first source | 2.44 | 2 | 0 | C-nitro compound; maleimides; monochlorobenzenes; phenols; secondary amino compound; substituted aniline | antioxidant; apoptosis inducer; EC 2.7.11.26 (tau-protein kinase) inhibitor; neuroprotective agent |
| dm 235 DM 235: structure in first source | 2.44 | 2 | 0 | ||
| jhw 015 [no description available] | 2.44 | 2 | 0 | indolecarboxamide | |
| bw 723c86 [no description available] | 2.44 | 2 | 0 | tryptamines | |
| sc 560 SC560 : A member of the class of pyrazoles that is 1H-pyrazole which is substituted at positions 1, 3 and 5 by 4-methoxyphenyl, trifluoromethyl and 4-chlorophenyl groups, respectively. Unlike many members of the diaryl heterocycle class of cyclooxygenase (COX) inhibitors, SC-560 is selective for COX-1. | 2.44 | 2 | 0 | aromatic ether; monochlorobenzenes; organofluorine compound; pyrazoles | angiogenesis modulating agent; antineoplastic agent; apoptosis inducer; cyclooxygenase 1 inhibitor; non-steroidal anti-inflammatory drug |
| sc-19220 [no description available] | 2.03 | 1 | 0 | aromatic ether | |
| le 300 [no description available] | 2.44 | 2 | 0 | indoles | |
| ly 367265 LY 367265: a 5-hydroxytryptamine transporter inhibitor; a 5-HT(2A) receptor antagonist; structure in first source. LY-367,265 : A fluoroindole that is 1H-indole in which the hydrogens at positions 3 and 6 are replaced by 1-[2-(2,2-dioxo-5,6-dihydro-4H-2lambda(6)-[1,2,5]thiadiazolo[4,3,2-ij]quinolin-1(2H)-yl)ethyl]-1,2,3,6-tetrahydropyridin-4-yl and fluoro groups, respectively. It is an inhibitor of the 5-hydroxytryptamine transporter (Ki = 2.3 nM) and an antagonist of 5-hydroxytryptamine(2A) receptor (Ki = 0.81 nM). | 2.44 | 2 | 0 | dihydropyridine; fluoroindole; tertiary amino compound; thiadiazoloquinoline | antidepressant; geroprotector; serotonergic antagonist; serotonin uptake inhibitor |
| diclofenac sodium Diclofenac Sodium: The sodium form of DICLOFENAC. It is used for its analgesic and anti-inflammatory properties.. diclofenac sodium : The sodium salt of diclofenac. | 2.03 | 1 | 0 | organic sodium salt | |
| cgp 7930 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol: structure in first source | 2.44 | 2 | 0 | alkylbenzene | |
| 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1h-pyrazole 4,4',4''-(4-propylpyrazole-1,3,5-triyl)trisphenol : A pyrazole that is 1H-pyrazole bearing three 4-hydroxyphenyl substituents at positions 1, 3 and 5 as well as a propyl substituent at position 4. Potent, subtype-selective estrogen receptor agonist (EC50 ~ 200 pM); displays 410-fold selectivity for ERalpha over ERbeta. Prevents ovariectomy-induced weight gain and loss of bone mineral density, and induces gene expression in the hypothalamus following systemic administration in vivo. | 2.44 | 2 | 0 | phenols; pyrazoles | estrogen receptor agonist |
| sib 1757 SIB 1757: a selective mGluR5 antagonist; structure in first source | 2.44 | 2 | 0 | ||
| sphingosine sphing-4-enine : A sphingenine in which the C=C double bond is located at the 4-position.. sphingenine : A 2-aminooctadecene-1,3-diol having (2S,3R)-configuration.. sphingoid : Sphinganine, its homologs and stereoisomers, and the hydroxy and unsaturated derivatives of these compounds.. 2-aminooctadec-4-ene-1,3-diol : A 2-aminooctadecene-1,3-diol having its double bond at position 4. | 2.03 | 1 | 0 | sphing-4-enine | human metabolite; mouse metabolite |
| apigenin Chamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia. | 2.44 | 2 | 0 | trihydroxyflavone | antineoplastic agent; metabolite |
| luteolin [no description available] | 2.03 | 1 | 0 | 3'-hydroxyflavonoid; tetrahydroxyflavone | angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; c-Jun N-terminal kinase inhibitor; EC 2.3.1.85 (fatty acid synthase) inhibitor; immunomodulator; nephroprotective agent; plant metabolite; radical scavenger; vascular endothelial growth factor receptor antagonist |
| daphnetin [no description available] | 2.44 | 2 | 0 | hydroxycoumarin | |
| genistein [no description available] | 2.03 | 1 | 0 | 7-hydroxyisoflavones | antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; geroprotector; human urinary metabolite; phytoestrogen; plant metabolite; tyrosine kinase inhibitor |
| pulmicort Budesonide: A glucocorticoid used in the management of ASTHMA, the treatment of various skin disorders, and allergic RHINITIS.. budesonide : A glucocorticoid steroid having a highly oxygenated pregna-1,4-diene structure. It is used mainly in the treatment of asthma and non-infectious rhinitis and for treatment and prevention of nasal polyposis. | 2.44 | 2 | 0 | 11beta-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; cyclic acetal; glucocorticoid; primary alpha-hydroxy ketone | anti-inflammatory drug; bronchodilator agent; drug allergen |
| timolol maleate (S)-timolol maleate : The maleic acid salt of the active (S)-enantiomer of timolol, comprising equimolar amounts of (S)-timolol and maleic acid. | 2.44 | 2 | 0 | maleate salt | anti-arrhythmia drug; antiglaucoma drug; antihypertensive agent; beta-adrenergic antagonist |
| brompheniramine maleate brompheniramine maleate : The maleic acid salt of brompheniramine. A histamine H1 receptor antagonist, it is used for the symptomatic relief of allergic conditions, including rhinitis and conjunctivitis. | 2.44 | 2 | 0 | maleate salt | anti-allergic agent |
| chlorpheniramine maleate [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| clemastine fumarate clemastine fumarate : The fumaric acid salt of clemastine. An antihistamine with antimuscarinic and moderate sedative properties, it is used for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin conditions. | 2.44 | 2 | 0 | fumarate salt | anti-allergic agent; antipruritic drug; H1-receptor antagonist; muscarinic antagonist |
| methylergonovine maleate [no description available] | 2.44 | 2 | 0 | ergoline alkaloid | geroprotector |
| astaxanthine astaxanthine: a keto form of carotene; pigment in flesh of Scottish salmon (Salmo salar) crustacoa-lobster (Homarus gammarus, flamingo feathers; structure; a carotenoid without vitamin A activity, has shown anti-oxidant and anti-inflammatory activities. astaxanthin : A carotenone that consists of beta,beta-carotene-4,4'-dione bearing two hydroxy substituents at positions 3 and 3' (the 3S,3'S diastereomer). A carotenoid pigment found mainly in animals (crustaceans, echinoderms) but also occurring in plants. It can occur free (as a red pigment), as an ester, or as a blue, brown or green chromoprotein. | 2.44 | 2 | 0 | carotenol; carotenone | animal metabolite; anticoagulant; antioxidant; food colouring; plant metabolite |
| harman harman: a beta-carboline; RN given refers to parent cpd; structure. harman : An indole alkaloid fundamental parent with a structure of 9H-beta-carboline carrying a methyl substituent at C-1. It has been isolated from the bark of Sickingia rubra, Symplocus racemosa, Passiflora incarnata, Peganum harmala, Banisteriopsis caapi and Tribulus terrestris, as well as from tobacco smoke. It is a specific, reversible inhibitor of monoamine oxidase A. | 2.44 | 2 | 0 | harmala alkaloid; indole alkaloid fundamental parent; indole alkaloid | anti-HIV agent; EC 1.4.3.4 (monoamine oxidase) inhibitor; plant metabolite |
| morin morin: a light yellowish pigment found in the wood of old fustic (Chlorophora tinctoria). morin : A pentahydroxyflavone that is 7-hydroxyflavonol bearing three additional hydroxy substituents at positions 2' 4' and 5. | 2.03 | 1 | 0 | 7-hydroxyflavonol; pentahydroxyflavone | angiogenesis modulating agent; anti-inflammatory agent; antibacterial agent; antihypertensive agent; antineoplastic agent; antioxidant; EC 5.99.1.2 (DNA topoisomerase) inhibitor; hepatoprotective agent; metabolite; neuroprotective agent |
| myricetin [no description available] | 2.44 | 2 | 0 | 7-hydroxyflavonol; hexahydroxyflavone | antineoplastic agent; antioxidant; cyclooxygenase 1 inhibitor; food component; geroprotector; hypoglycemic agent; plant metabolite |
| daidzein [no description available] | 2.03 | 1 | 0 | 7-hydroxyisoflavones | antineoplastic agent; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; EC 3.2.1.20 (alpha-glucosidase) inhibitor; phytoestrogen; plant metabolite |
| caffeic acid phenethyl ester phenethyl caffeate : An alkyl caffeate ester in which 2-phenylethyl is the alkyl component. | 2.44 | 2 | 0 | alkyl caffeate ester | anti-inflammatory agent; antibacterial agent; antineoplastic agent; antioxidant; antiviral agent; immunomodulator; metabolite; neuroprotective agent |
| rottlerin rottlerin: an angiogenesis inhibitor; an inhibitor of protein kinase Cdelta (PKCdelta) and calmodulin kinase III; RN refers to (E)-isomer; do not confuse this chalcone with an anthraquinone that is also called rottlerin (RN 481-72-1);. rottlerin : A chromenol that is 2,2-dimethyl-2H-chromene substituted by hydroxy groups at positions 5 and 7, a 3-acetyl-2,4,6-trihydroxy-5-methylbenzyl group at position 6 and a (1E)-3-oxo-1-phenylprop-1-en-3-yl group at position 8. A potassium channel opener, it is isolated from Mallotus philippensis. | 2.44 | 2 | 0 | aromatic ketone; benzenetriol; chromenol; enone; methyl ketone | anti-allergic agent; antihypertensive agent; antineoplastic agent; apoptosis inducer; K-ATP channel agonist; metabolite |
| flupenthixol cis-flupenthixol : A flupenthixol in which the double bond adopts a cis-configuration. | 2.03 | 1 | 0 | flupenthixol | dopaminergic antagonist |
| n-oleoyldopamine N-oleoyldopamine: putative capsaicin receptor ligand; produces hyperalgesia; isolated from the brain. N-oleoyldopamine : A fatty amide resulting from the formal condensation of the carboxy group of oleic acid with the amino group of dopamine. Synthesised in catecholaminergic neurons, it crosses the blood-brain barrier and might be considered as a carrier of dopamine into the brain. It is a transient receptor potential vanilloid type 1 (TRPV1) receptor agonist. | 2.44 | 2 | 0 | catechols; fatty amide; N-(fatty acyl)-dopamine; secondary carboxamide | TRPV1 agonist |
| pheniramine maleate Naphcon A: tradename; contains above compounds; ophthalmic solution | 2.44 | 2 | 0 | organic molecular entity | |
| tranilast tranilast: antiallergic drug; potent inhibitor of homologous passive cutaneous anaphylaxis. tranilast : An amidobenzoic acid that is anthranilic acid in which one of the anilino hydrogens is replaced by a 3,4-dimethoxycinnamoyl group. | 2.44 | 2 | 0 | amidobenzoic acid; cinnamamides; dimethoxybenzene; secondary carboxamide | anti-allergic agent; anti-asthmatic drug; antineoplastic agent; aryl hydrocarbon receptor agonist; calcium channel blocker; hepatoprotective agent; nephroprotective agent |
| trimipramine maleate [no description available] | 2.44 | 2 | 0 | maleate salt | antidepressant |
| isotretinoin Isotretinoin: A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.. isotretinoin : A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases. | 2.44 | 2 | 0 | retinoic acid | antineoplastic agent; keratolytic drug; teratogenic agent |
| xylometazoline hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| flunarizine hydrochloride [no description available] | 2.44 | 2 | 0 | diarylmethane | |
| ketotifen fumarate ketotifen fumarate : An organoammonium salt consisting of equimolar amounts of ketotifen(1+) and fumarate(1-) ions. A blocker of histamine H1 receptors with a stabilising action on mast cells, it is a non-bronchodilator anti-asthmatic drug. | 2.44 | 2 | 0 | organoammonium salt | anti-asthmatic drug; H1-receptor antagonist |
| cis-flupenthixol dihydrochloride cis-flupenthixol dihydrochloride : The dihydrochloride salt of cis-flupenthixol. | 2.44 | 2 | 0 | hydrochloride | geroprotector |
| n-arachidonylglycine N-arachidonylglycine: structure in first source. N-arachidonoylglycine : Biologically active derivative of anandamide | 2.44 | 2 | 0 | fatty amide; N-acylglycine | |
| n-oleoylethanolamine N-oleoylethanolamine: ceramidase inhibitor. oleoyl ethanolamide : An N-(long-chain-acyl)ethanolamine that is the ethanolamide of oleic acid. The monounsaturated analogue of the endocannabinoid anandamide. | 2.44 | 2 | 0 | endocannabinoid; N-(long-chain-acyl)ethanolamine; N-acylethanolamine 18:1 | EC 3.5.1.23 (ceramidase) inhibitor; geroprotector; PPARalpha agonist |
| cyclosporine ramihyphin A: one of the metabolites produced by Fusarium sp. S-435; RN given refers to cpd with unknown MF | 2.44 | 2 | 0 | homodetic cyclic peptide | anti-asthmatic drug; anticoronaviral agent; antifungal agent; antirheumatic drug; carcinogenic agent; dermatologic drug; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; geroprotector; immunosuppressive agent; metabolite |
| phenoxybenzamine hydrochloride [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| phenylephrine hydrochloride Nose: A part of the upper respiratory tract. It contains the organ of SMELL. The term includes the external nose, the nasal cavity, and the PARANASAL SINUSES.. phenylephrine hydrochloride : A hydrochloride that is the monohydrochloride salt of phenylephrine. | 2.03 | 1 | 0 | hydrochloride | |
| mepyramine maleate histosol: proprietary mixture of synthetic aromatic hydrocarbons forming an extremely nonpolar organic solvent | 2.44 | 2 | 0 | ||
| brefeldin a [no description available] | 2.44 | 2 | 0 | macrolide antibiotic | Penicillium metabolite |
| fenretinide Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.. 4-hydroxyphenyl retinamide : A retinoid obtained by formal condensation of the carboxy group of all-trans retinoic acid and the anilino group of 4-hydroxyaniline. Synthetic retinoid agonist. Antiproliferative, antioxidant and anticancer agent with a long half-life in vivo. Apoptotic effects appear to be mediated by a mechanism distinct from that of 'classical' retinoids. | 2.44 | 2 | 0 | monocarboxylic acid amide; retinoid | antineoplastic agent; antioxidant |
| su 9516 [no description available] | 2.05 | 1 | 0 | ||
| 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid: RN refers to (E)-isomer; structure given in first source. arotinoid acid : A retinoid that consists of benzoic acid substituted at position 4 by a 2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)prop-1-en-1-yl group. It is a synthetic retinoid that acts as a selective agonist for the retinoic acid receptors (RAR). | 2.44 | 2 | 0 | benzoic acids; naphthalenes; retinoid | antineoplastic agent; retinoic acid receptor agonist; teratogenic agent |
| l-2-(carboxypropyl)glycine [no description available] | 2.03 | 1 | 0 | ||
| 4-aminocrotonic acid [no description available] | 2.03 | 1 | 0 | ||
| denopamine denopamine: structure given in first source | 2.03 | 1 | 0 | dimethoxybenzene | |
| l 655,708 [no description available] | 2.44 | 2 | 0 | ||
| ml 10302 2-piperidinoethyl 4-amino-5-chloro-2-methoxybenzoate: structure in first source | 2.05 | 1 | 0 | ||
| ro 41-1049 Ro 41-1049: structure given in first source | 2.03 | 1 | 0 | ||
| sb 200646a [no description available] | 2.44 | 2 | 0 | ||
| seglitide seglitide: more potent than somatostatin for inhibition of insulin, glucagon & growth hormone release; used experimentally in treatment of Alzheimer's disease; somatostatin receptor antagonist | 2.03 | 1 | 0 | ||
| sib 1893 SIB 1893: a selective mGluR5 antagonist; structure in first source | 2.03 | 1 | 0 | ||
| su 6656 SU 6656: a c-Src kinase inhibitor; used to probe growth signaling; structure in first source. SU6656 : A member of the class of oxindoles that is 3-methyleneoxindole in which the hydrogeh at position 5 has been replaced by a dimethylaminosulfonyl group and in which one of the hydrogens of the methylene group has been replaced by a 4,5,6,7-tetrahydro-indol-2-yl group. It is a specific inhibitor of Src family kinase. | 2.44 | 2 | 0 | ||
| ag 538 AG 538: an IGF-1 receptor kinase inhibitor; structure in first source | 2.05 | 1 | 0 | ||
| tyrphostin ag 555 [no description available] | 2.44 | 2 | 0 | ||
| tyrphostin ag-494 AG 494: tyrphostin that blocks Cdk2 activation; structure in first source | 2.03 | 1 | 0 | ||
| tyrphostin b44 tyrphostin B44: inhibits protein kinases; an analog of tyrphostin B46; B44(+) is B50, and is the stereoisomer of B44(-) | 2.44 | 2 | 0 | ||
| ag-490 [no description available] | 2.44 | 2 | 0 | catechols; enamide; monocarboxylic acid amide; nitrile; secondary carboxamide | anti-inflammatory agent; antioxidant; apoptosis inducer; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; geroprotector; STAT3 inhibitor |
| ag 112 [no description available] | 2.44 | 2 | 0 | ||
| ag 183 AG 183: structure given in first source | 2.44 | 2 | 0 | ||
| semaxinib semaxanib : An oxindole that is 3-methyleneoxindole in which one of the hydrogens of the methylene group is replaced by a 3,5-dimethylpyrrol-2-yl group. | 2.44 | 2 | 0 | olefinic compound; oxindoles; pyrroles | angiogenesis modulating agent; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; vascular endothelial growth factor receptor antagonist |
| 8-(3-chlorostyryl)caffeine 8-(3-chlorostyryl)caffeine: adenosine antagonist. 8-(3-chlorostyryl)caffeine : Caffeine substituted at its 8-position by an (E)-3-chlorostyryl group. | 2.44 | 2 | 0 | monochlorobenzenes; trimethylxanthine | adenosine A2A receptor antagonist; EC 1.4.3.4 (monoamine oxidase) inhibitor |
| bay 11-7085 BAY11-7085 : A sulfone that is benzene substituted by [(E)-2-cyanoethenyl]sulfonyl and tert-butyl groups at position 1 and 4, respectively. It is an irreversible inhibitor of IkappaB-alpha phosphorylation in cells (IC50 = 10 muM) and prevents the activation of NF-kappaB. | 2.44 | 2 | 0 | benzenes; nitrile; sulfone | anti-inflammatory agent; antibacterial agent; antineoplastic agent; apoptosis inducer; autophagy inducer; EC 2.7.11.10 (IkappaB kinase) inhibitor; ferroptosis inducer; NF-kappaB inhibitor |
| bw b70c BW B70C: arachidonic acid antagonist. BW B70C : A hydroxamic acid that is urea in which both the hydrogens attached to one of the nitrogens are replaced by a hydroxy and a (1E)-1-[3-(4-fluorophenoxy)phenyl]but-1-en-3-yl group. A selective inhibitor of arachidonate 5-lipoxygenase, it can be used for the treatment of asthma. | 2.05 | 1 | 0 | aromatic ether; hydroxamic acid; organofluorine compound; ureas | EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor |
| molsidomine [no description available] | 2.03 | 1 | 0 | ethyl ester; morpholines; oxadiazole; zwitterion | antioxidant; apoptosis inhibitor; cardioprotective agent; nitric oxide donor; vasodilator agent |
| diamide Diamide: A sulfhydryl reagent which oxidizes sulfhydryl groups to the disulfide form. It is a radiation-sensitizing agent of anoxic bacterial and mammalian cells. | 2.03 | 1 | 0 | 1,1'-azobis(N,N-dimethylformamide) | |
| nomifensine maleate [no description available] | 2.44 | 2 | 0 | ||
| nalbuphine hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | |
| isoalloxazine isoalloxazine: structure | 2.03 | 1 | 0 | benzo[g]pteridine-2,4-dione | |
| vinblastine sulfate [no description available] | 2.44 | 2 | 0 | ||
| n-methylscopolamine bromide scopolamine methobromide : A quaternary ammonium salt resulting from the reaction of the amino group of scopolamine with methyl bromide. | 2.03 | 1 | 0 | ||
| dextromethorphan hydrobromide dextromethorphan hydrobromide : The hydrobromide and monohydrate of the antitussive drug dextromethorphan. | 2.44 | 2 | 0 | hydrate; hydrobromide | |
| naloxone hydrochloride naloxone hydrochloride : A hydrochloride resulting from the formal reaction of equimolar amounts of naloxone and hydrogen chloride. A specific opioid antagonist, it is used to reverse the effects of opioids, both following their use of opioids during surgery and in cases of known or suspected opioid overdose. | 2.03 | 1 | 0 | hydrochloride | antidote to opioid poisoning; central nervous system depressant; mu-opioid receptor antagonist |
| s-trans,trans-farnesylthiosalicylic acid farnesylthiosalicylic acid: structure in first source | 2.44 | 2 | 0 | sesquiterpenoid | |
| sulindac sulfone sulindac sulfone: inhibits K-ras-dependent cyclooxygenase-2; sulfated analog of indomethacin;; CP248 is an antineoplastic agent that fosters microtubule depolymerization; structure in first source. sulindac sulfone : A sulfone metabolite of sulindac that inhibits cell growth by inducing apoptosis independently of cyclooxygenase inhibition. It inhibits the development and induces regression of premalignant adenomatous polyps. Lipoxygenase and Cox-2 inhibitor. | 2.03 | 1 | 0 | monocarboxylic acid; organofluorine compound; sulfone | apoptosis inducer; cyclooxygenase 2 inhibitor; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor |
| naltrexone hydrochloride naltrexone hydrochloride : A hydrochloride obtained by reaction of oxycodone with one molar equivalent of hydrochloric acid. it is a mu-opioid receptor antagonist that is used to treat alcohol dependence. | 2.44 | 2 | 0 | hydrochloride | antidote to opioid poisoning; central nervous system depressant; mu-opioid receptor antagonist |
| guanabenz acetate [no description available] | 2.44 | 2 | 0 | dichlorobenzene | geroprotector |
| nylidrin hydrochloride [no description available] | 2.44 | 2 | 0 | alkylbenzene | |
| triprolidine hydrochloride anhydrous triprolidine hydrochloride (anh.) : A hydrochloride resulting from the formal reaction of equimolar amounts of triprolidine and hydrogen chloride. Its monohydrate is used for the symptomatic relief of uticaria, rhinitis, and various pruritic skin disorders. | 2.44 | 2 | 0 | hydrochloride | H1-receptor antagonist |
| famotidine [no description available] | 2.03 | 1 | 0 | 1,3-thiazoles; guanidines; sulfonamide | anti-ulcer drug; H2-receptor antagonist; P450 inhibitor |
| fenoterol fenoterol hydrobromide : The hydrobromide salt of fenoterol. A beta2-adrenergic agonist, it is used as a bronchodilator in the management of reversible airway obstruction. | 2.03 | 1 | 0 | hydrobromide | beta-adrenergic agonist; bronchodilator agent; sympathomimetic agent |
| tiapridex Tiapride Hydrochloride: A benzamide derivative that is used as a dopamine antagonist. | 2.03 | 1 | 0 | benzamides | |
| quipazine maleate [no description available] | 2.44 | 2 | 0 | ||
| n-(2-aminoethyl)-4-chlorobenzamide hydrochloride Ro 16-6491: structure given in first source | 2.03 | 1 | 0 | ||
| tulobuterol hydrochloride [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| hp 029 [no description available] | 2.44 | 2 | 0 | ||
| n,n,n-trimethyl-1-(4-stilbenoxy)-2-propylammonium iodide [no description available] | 2.03 | 1 | 0 | ||
| 6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2h-pyran-2-one 6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one: structure given in first source; potent irreversible, mechanism-based inhibitor of myocardial calcium-independent phospholipase A2 | 2.44 | 2 | 0 | naphthalenes | |
| nf023 [no description available] | 2.03 | 1 | 0 | ||
| nf 449 [no description available] | 2.44 | 2 | 0 | ||
| 7-chloro-4-hydroxy-2-phenyl-1,8-naphthyridine [no description available] | 2.44 | 2 | 0 | ||
| gr 46611 GR 46611: known to lower body temperature in guinea pigs | 2.03 | 1 | 0 | ||
| diacetylmonoxime diacetylmonoxime: used diagnostically for determining urea in blood; structure; myosin ATPase antagonist. diacetylmonoxime : A ketoxime obtained via formal condensation of butane-2,3-dione with hydroxylamine. It is a reversible myosin ATPase inhibitor. | 2.03 | 1 | 0 | ||
| homatropine hydrobromide, (endo-(+-)-isomer) [no description available] | 2.44 | 2 | 0 | ||
| vancomycin hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| moxisylyte hydrochloride [no description available] | 2.03 | 1 | 0 | monoterpenoid | |
| dizocilpine maleate Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.. dizocilpine maleate : A maleate salt obtained by reaction of dizocilpine with one equivalent of maleic acid. | 2.44 | 2 | 0 | maleate salt; tetracyclic antidepressant | anaesthetic; anticonvulsant; neuroprotective agent; nicotinic antagonist; NMDA receptor antagonist |
| beta-aminopropionitrile fumarate beta-aminopropionitrile fumarate: RN given refers to unspecified fumarate | 2.03 | 1 | 0 | ||
| mg 624 triethyl-(beta-4-stilbenoxyethyl)ammonium: inhibits alpha7 nicotinic receptors; structure in first source | 2.05 | 1 | 0 | ||
| flupirtine [no description available] | 2.44 | 2 | 0 | ||
| zimelidine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| pregna-4,17-diene-3,16-dione, (17z)-isomer [no description available] | 2.44 | 2 | 0 | ||
| su 4312 SU4312 : A member of the class of oxindoles that is 3-methyleneoxindole in which one of the hydrogens of the methylene group has been replaced by a p-(dimethylamino)phenyl group. SU 4312 is a vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 and platelet derived growth factor (PDGF) receptor inhibitor. It also inhibits the neuronal nitric oxide synthase (NOS) and exhibits neuroprotection against NO-mediated neurotoxicity. | 2.44 | 2 | 0 | ||
| gw 1929 GW 1929: activates peroxisome proliferator-activated receptor-gamma; structure in first source | 2.44 | 2 | 0 | benzophenones | |
| protriptyline hydrochloride [no description available] | 2.44 | 2 | 0 | hydrochloride | antidepressant |
| n(4)-chloroacetylcytosine arabinoside [no description available] | 2.03 | 1 | 0 | ||
| n-(3-(cyclohexylidene-(1h-imidazol-4-ylmethyl))phenyl)ethanesulfonamide [no description available] | 2.44 | 2 | 0 | ||
| n-(4-amino-2-chlorophenyl)phthalimide N-(4-amino-2-chlorophenyl)phthalimide: has anticonvulsant activity; structure in first source | 2.03 | 1 | 0 | ||
| cb 34 CB 34: ligand for peripheral benzodiazepine receptors; structure in first source | 2.03 | 1 | 0 | ||
| b 43 RK-24466 : A member of the class of pyrrolopyrimidines that is 7H-pyrrolo[2,3-d]pyrimidine substituted by amino, 4-phenoxyphenyl, and cyclopentyl groups at positions 4, 5 and 7, respectively. It is a potent inhibitor of Lck that inhibits Lck (64-509) and LckCD isoforms (IC50 of less than 1 and 2 nM, respectively). | 2.44 | 2 | 0 | aromatic amine; aromatic ether; cyclopentanes; primary amino compound; pyrrolopyrimidine | EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; geroprotector |
| (8R)-7-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,13,14-triol [no description available] | 2.03 | 1 | 0 | aporphine alkaloid | |
| (8R)-7-propyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,13,14-triol [no description available] | 2.03 | 1 | 0 | aporphine alkaloid | |
| 3-(6-chloro-3-pyridazinyl)-3,8-diazabicyclo(3.2.1)octane 3-(6-chloro-3-pyridazinyl)-3,8-diazabicyclo(3.2.1)octane: structure in first source | 2.03 | 1 | 0 | ||
| 2-(3,3-diphenylpropylamino)acetamide [no description available] | 2.44 | 2 | 0 | diarylmethane | |
| 4-(2-(phenylsulfonylamino)ethylthio)-2,6-difluorophenoxyacetamide 4-(2-(phenylsulfonylamino)ethylthio)-2,6-difluorophenoxyacetamide: structure given in first source | 2.03 | 1 | 0 | ||
| gw2974 GW2974: quinazoline derivative, which is able to block the activation of both the EGFR and erbB2 | 2.03 | 1 | 0 | pyridopyrimidine | |
| 7-hydroxy-2-n,n-dipropylaminotetralin, (r)-isomer [no description available] | 2.13 | 1 | 0 | ||
| l 162313 L 162313: a biphenylimidazole derivative; a non-peptide angiotensin agonist; no further information available 2/95 | 2.44 | 2 | 0 | ||
| l-165041 4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid: a PPAR-delta agonist has regulatory effects on a variety of adipokines, and these effects might explain some of their metabolic function. | 2.03 | 1 | 0 | aromatic ketone | |
| mrs 1754 [no description available] | 2.03 | 1 | 0 | oxopurine | |
| s-nitroso-n-acetylpenicillamine S-Nitroso-N-Acetylpenicillamine: A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS. | 2.03 | 1 | 0 | nitroso compound; nitrosothio compound | nitric oxide donor; vasodilator agent |
| pd 404182 [no description available] | 2.03 | 1 | 0 | ||
| 5-(4-phenylbutoxy)psoralen 5-(4-phenylbutoxy)psoralen: structure in first source. psora 4 : A member of the class of psoralens that is psoralen substituted by a 4-phenylbutoxy group at position 5. It is a potent inhibitor of the voltage-gated potassium channel Kv1.3 (EC50 = 3 nM). | 2.05 | 1 | 0 | aromatic ether; benzenes; psoralens | geroprotector; immunosuppressive agent; potassium channel blocker |
| sb 222200 [no description available] | 2.44 | 2 | 0 | quinolines | |
| dantrolene sodium dantrolene sodium (anhydrous) : The anhydrous sodium salt of dantrolene. | 2.44 | 2 | 0 | ||
| cr 2945 CR 2945: a member of non-peptide CCKB receptor antagonist | 2.44 | 2 | 0 | ||
| sb 218795 SB 218795: structure in first source | 2.44 | 2 | 0 | quinolines | |
| dihydroceramide N-acetylsphinganine : A dihydroceramide in which the ceramide acyl group is specified as acetyl. | 2.03 | 1 | 0 | N-acylsphinganine | |
| epinephrine bitartrate [no description available] | 2.44 | 2 | 0 | ||
| bicuculline methobromide [no description available] | 2.44 | 2 | 0 | ||
| butylscopolammonium bromide Butylscopolammonium Bromide: Antimuscarinic quaternary ammonium derivative of scopolamine used to treat cramps in gastrointestinal, urinary, uterine, and biliary tracts, and to facilitate radiologic visualization of the gastrointestinal tract. | 2.03 | 1 | 0 | ||
| butaclamol hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| a 38503 [no description available] | 2.44 | 2 | 0 | ||
| bisoprolol, fumarate (1:1) salt [no description available] | 2.05 | 1 | 0 | ||
| 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide [no description available] | 2.03 | 1 | 0 | ||
| sk&f 89976-a [no description available] | 2.03 | 1 | 0 | ||
| cv 1808 2-phenylaminoadenosine: has coronary & cardiohemodynamic effects | 2.44 | 2 | 0 | purine nucleoside | |
| 8-(n,n-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride [no description available] | 2.05 | 1 | 0 | ||
| indacaterol indacaterol: a beta2 adrenoceptor agonist; indacaterol is the (R)-isomer; structure in first source. indacaterol : A monohydroxyquinoline that consists of 5-[(1R)-2-amino-1-hydroxyethyl]-8-hydroxyquinolin-2-one having a 5,6-diethylindan-2-yl group attached to the amino function. Used as the maleate salt for treatment of chronic obstructive pulmonary disease. | 3.33 | 6 | 0 | indanes; monohydroxyquinoline; quinolone; secondary alcohol; secondary amino compound | beta-adrenergic agonist; bronchodilator agent |
| fluvoxamine maleate [no description available] | 2.44 | 2 | 0 | (trifluoromethyl)benzenes | |
| naloxone benzoylhydrazone [no description available] | 2.44 | 2 | 0 | ||
| 2-methyl-6-(phenylethynyl)pyridine hydrochloride 2-methyl-6-(phenylethynyl)pyridine hydrochloride : A hydrochloride salt obtained by reaction of 2-methyl-6-(phenylethynyl)pyridine with one equivalent of hydrochloric acid. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw. | 2.44 | 2 | 0 | hydrochloride | anxiolytic drug; metabotropic glutamate receptor antagonist |
| amiprilose [no description available] | 2.03 | 1 | 0 | ||
| (R)-fluoxetine hydrochloride (R)-fluoxetine hydrochloride : A hydrochloride obtained by reaction of (R)-fluoxetine with one equivalent of hydrochloric acid. | 2.44 | 2 | 0 | hydrochloride | antidepressant; serotonin uptake inhibitor |
| ro 8-4304 [no description available] | 2.05 | 1 | 0 | ||
| l 755507 L 755507: a benzenesulfonamide derivative; structure in first source | 2.97 | 1 | 0 | ||
| desmethylselegiline hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| 3-morpholino-sydnonimine monohydrochloride [no description available] | 2.44 | 2 | 0 | ||
| t 1032 T 1032: a cyclic GMP phosphodiesterase-5 inhibitor; structure in first source | 2.44 | 2 | 0 | ||
| qx-314 bromide [no description available] | 2.03 | 1 | 0 | ||
| (S)-fluoxetine hydrochloride (S)-fluoxetine hydrochloride : A hydrochloride obtained by reaction of (S)-fluoxetine with one equivalent of hydrochloric acid. | 2.44 | 2 | 0 | hydrochloride | antidepressant; serotonin uptake inhibitor |
| sr 59230a 3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate: structure given in first source | 2.44 | 2 | 0 | ||
| u 74389g [no description available] | 2.44 | 2 | 0 | ||
| 1-(2-methoxyphenyl)piperazine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| y 27632, dihydrochloride, (4(r)-trans)-isomer [no description available] | 2.03 | 1 | 0 | ||
| sb 203186 [no description available] | 2.05 | 1 | 0 | ||
| noscapine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| a 77636 (1R,3S)-3-(adamantan-1-yl)-1-(aminomethyl)-3,4-dihydroisochromene-5,6-diol hydrochloride : A hydrochloride salt obtained by mixing equimolar amounts of (1R,3S)-3-(adamantan-1-yl)-1-(aminomethyl)-3,4-dihydroisochromene-5,6-diol with hydrochloric acid. Potent and selective dopamine D1-like receptor agonist (pEC50 values are 8.97 and < 5 for D1-like and D2-like receptors respectively). Displays anti-Parkinsonian activity following oral administration in vivo. | 2.44 | 2 | 0 | hydrochloride | antiparkinson drug; dopamine agonist |
| cgp 20712a CGP 20712A: structure given in first source; CGP 26505, a beta1-selective beta-adrenoceptor antagonist, is the (S)-isomer of CGP 20712A | 2.44 | 2 | 0 | ||
| levodopa methyl ester hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| benalfocin hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| lu 19005 [no description available] | 2.44 | 2 | 0 | ||
| benoxathian hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| ((2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1h-inden-5-yl)oxy)acetic acid, (+)-isomer [no description available] | 2.44 | 2 | 0 | ||
| n-cyclopropyl adenosine-5'-carboxamide [no description available] | 2.03 | 1 | 0 | ||
| cefotaxime sodium [no description available] | 2.03 | 1 | 0 | organic sodium salt | |
| calpain inhibitor iii calpain inhibitor III: potential anticataract drug | 2.44 | 2 | 0 | ||
| 5-hydroxy-2-n,n-dipropylaminotetralin, (s)-isomer [no description available] | 2.13 | 1 | 0 | ||
| tiotropium bromide tiotropium bromide hydrate : A hydrate that is the monohydrate form of tiotropium bromide. Used for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease. | 2.06 | 1 | 0 | ||
| GR 127935 hydrochloride GR 127935 hydrochloride : A hydrochloride obtained by reaction of GR 127935 with one equivalent of hydrochloric acid. Potent and selective 5-HT1B/1D receptor antagonist (pKi values are 8.5 for both guinea pig 5-HT1D and rat 5-HT1B receptors). Displays > 100-fold selectivity over 5HT1A, 5-HT2A, 5-HT2C receptors and other receptor types. Centrally active following oral administration. | 2.44 | 2 | 0 | hydrochloride | serotonergic antagonist |
| mrs 1845 [no description available] | 2.44 | 2 | 0 | ||
| 1-aminocyclopropane-1-carboxylic acid hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| alaproclate hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| ubenimex [no description available] | 2.44 | 2 | 0 | peptide | |
| 3-chloroalanine hydrochloride, (l-ala)-isomer [no description available] | 2.03 | 1 | 0 | ||
| dsp 4 hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| calcimycin Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems. | 2.44 | 2 | 0 | benzoxazole | |
| (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzodioxan hydrochloride N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine hydrochloride : A hydrochloride salt that is obtained by reaction of N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-2-(2,6-dimethoxyphenoxy)ethanamine with one equivalent of hydrogen chloride. An alpha1A-adrenergic selective antagonist. | 2.44 | 2 | 0 | hydrochloride | alpha-adrenergic antagonist |
| 2-cyclooctyl-2-hydroxyethylamine hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| cirazoline monohydrochloride [no description available] | 2.44 | 2 | 0 | ||
| adtn [no description available] | 2.44 | 2 | 0 | ||
| apocodeine hydrochloride, (r)-isomer [no description available] | 2.44 | 2 | 0 | ||
| 2-hydroxyapomorphine, (r)-isomer [no description available] | 2.05 | 1 | 0 | ||
| Dihydro-beta-erythroidine hydrobromide [no description available] | 2.03 | 1 | 0 | indoles | |
| lilly 78335 [no description available] | 2.44 | 2 | 0 | ||
| efaroxan hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| fenoldopam hydrobromide [no description available] | 2.44 | 2 | 0 | ||
| 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride : A hydrochloride salt that is obtained by reaction of 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine with two equivalents of hydrogen chloride. Potent and selective inhibitor of dopamine uptake (KD = 5.5 nM in rat striatal membranes). | 2.44 | 2 | 0 | hydrochloride | dopamine uptake inhibitor |
| guvacine hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| 7-hydroxy-2-n,n-dipropylaminotetralin hydrobromide [no description available] | 2.44 | 2 | 0 | ||
| 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide, (r)-isomer, [no description available] | 2.44 | 2 | 0 | organic molecular entity | |
| 1-(2-(4-(4-fluoro-benzoyl)-piperidin-1-yl)-ethyl)-3,3-dimethyl-1,2-dihydro-indol-2-one LY-310762 hydrochloride : A hydrochloride resulting from the formal reation of equimolar amount of LY-310762 with hydrogen chloride. A potent and selective antagonist for the 5-hydroxytryptamine 1D (5-HT1D) receptor. | 2.44 | 2 | 0 | hydrochloride | receptor modulator; serotonergic antagonist |
| 4-iodoclonidine [no description available] | 2.44 | 2 | 0 | ||
| 4-methylpyrazole monohydrochloride [no description available] | 2.03 | 1 | 0 | ||
| tele-methylhistamine [no description available] | 2.03 | 1 | 0 | ||
| alpha-methyltyrosine methyl ester, monohydrochloride [no description available] | 2.44 | 2 | 0 | ||
| octoclothepine maleate [no description available] | 2.44 | 2 | 0 | ||
| 2-(n-phenethyl-n-propyl)amino-5-hydroxytetralin hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| du 24565 [no description available] | 2.44 | 2 | 0 | ||
| 2-methoxyidazoxan hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| N-methyl-6-chloro-1-(3-methylphenyl)-2,3,4,5-tetrahydro-3-benzazepine-7,8-diol hydrobromide N-methyl-6-chloro-1-(3-methylphenyl)-2,3,4,5-tetrahydro-3-benzazepine-7,8-diol hydrobromide : A hydrobromide salt prepared from N-methyl-6-chloro-1-(3-methylphenyl)-2,3,4,5-tetrahydro-3-benzazepine-7,8-diol and one equivalent of hydrogen bromide. Dopamine D1-like receptor partial agonist (Ki values are 1.18, 7.56, 920 and 399 nM for rat D1, D5, D2 and D3 receptors respectively). May act as an antagonist in vivo, producing anti-Parkinsonian effects and antagonising the behavioral effects of cocaine. | 2.05 | 1 | 0 | hydrobromide | dopamine agonist; prodrug |
| ro 25-6981 [no description available] | 2.44 | 2 | 0 | ||
| sk&f 77434 N-allyl-1-phenyl-2,3,4,5-tetrahydro-3-benzazepine-7,8-diol hydrobromide : A hydrobromide salt prepared from N-allyl-1-phenyl-2,3,4,5-tetrahydro-3-benzazepine-7,8-diol and one equivalent of hydrogen bromide. Selective dopamine D1-like receptor partial agonist (IC50 values are 19.7 and 2425 nM for binding to D1-like and D2-like receptors respectively). Centrally active following systemic administration in vivo. | 2.44 | 2 | 0 | hydrobromide | dopamine agonist; prodrug |
| 3-[(6aR,9R,10aR)-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-yl]-1,1-diethylurea [no description available] | 2.44 | 2 | 0 | organic heterotetracyclic compound; organonitrogen heterocyclic compound | |
| demethylcantharidin demethylcantharidin: has antineoplastic activity; structure in first source | 2.44 | 2 | 0 | ||
| atropine sulfate [no description available] | 2.44 | 2 | 0 | ||
| 1-deoxynojirimycin hydrochloride [no description available] | 2.03 | 1 | 0 | ||
| win 62577 [no description available] | 2.44 | 2 | 0 | ||
| quinine sulfate [no description available] | 2.44 | 2 | 0 | hydrate | |
| quercetin [no description available] | 2.44 | 2 | 0 | ||
| rv 538, (r-(r*,r*))-isomer [no description available] | 2.44 | 2 | 0 | ||
| 3,4-dichloro-n-methyl-n-(2-(1-pyrrolidinyl)cyclohexyl)-benzeneacetamide, (1s-cis)-isomer [no description available] | 2.44 | 2 | 0 | ||
| valproate sodium Epilim: oral sodium valproate used as antidepressive agent. sodium valproate : The sodium salt of valproic acid.. valproate : A branched-chain saturated fatty acid anion that is the conjugate base of valproic acid. | 2.03 | 1 | 0 | organic sodium salt | geroprotector |
| u 63557a [no description available] | 2.03 | 1 | 0 | ||
| taurocholic acid, monosodium salt [no description available] | 2.44 | 2 | 0 | bile salt | |
| cefmetazole sodium cefmetazole sodium : An organic sodium salt that is the sodium salt of cefmetazole. | 2.03 | 1 | 0 | organic sodium salt | antimicrobial agent |
| fusidate sodium [no description available] | 2.44 | 2 | 0 | ||
| cephapirin sodium cephapirin sodium : The sodium salt of cephapirin. A first-generation cephalosporin antibiotic, it is effective against gram-negative and gram-positive organisms. Being more resistant to beta-lactamases than penicillins, it is effective agains most staphylococci, though not methicillin-resistant staphylococci. | 2.03 | 1 | 0 | cephalosporin; organic sodium salt | antibacterial drug |
| sodium cephalothin [no description available] | 2.03 | 1 | 0 | organic sodium salt | |
| cefazolin sodium cefazolin sodium : A cephalosporin organic sodium salt having [(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl and (1H-tetrazol-1-ylacetyl)amino side-groups. | 2.44 | 2 | 0 | organic sodium salt | |
| 5-hydroxydecanoic acid, monosodium salt [no description available] | 2.03 | 1 | 0 | ||
| ro13-9904 Ceftriaxone: A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.. ceftriaxone : A third-generation cephalosporin compound having 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetylamino and [(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl side-groups. | 2.03 | 1 | 0 | ||
| phenytoin sodium [no description available] | 2.03 | 1 | 0 | ||
| cr 1409 lorglumide sodium : A racemate comprising equal amounts of (R)- and (S)-lorglumide sodium. | 2.03 | 1 | 0 | ||
| cortisol succinate, sodium salt hydrocortisone hemisuccinate: RN given refers to (11beta)-isomer; Synonyms Solu-Cortef & sopolcort H refer to Na salt | 2.44 | 2 | 0 | organic molecular entity | |
| bi167107 BI167107: structure in first source | 2.05 | 1 | 0 | ||
| piroxicam [no description available] | 2.44 | 2 | 0 | benzothiazine; monocarboxylic acid amide; pyridines | analgesic; antirheumatic drug; cyclooxygenase 1 inhibitor; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; non-steroidal anti-inflammatory drug |
| lfm a13 LFM-A13 : An enamide obtained by formal condensation of the carboxy group of (2Z)-2-cyano-3-hydroxybut-2-enoic acid with the amino group of 2,5-dibromoaniline. It is a dual-function inhibitor of Bruton's tyrosine kinase (BTK) and Polo-like kinases (PLK) that exhibits anticancer properties. | 2.03 | 1 | 0 | aromatic amide; dibromobenzene; enamide; enol; nitrile; secondary carboxamide | antineoplastic agent; apoptosis inducer; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 2.7.11.21 (polo kinase) inhibitor; geroprotector; platelet aggregation inhibitor |
| l 701324 L 701324: a glycine/NMDA receptor antagonist | 2.03 | 1 | 0 | quinolines | |
| hispidin hispidin: metabolite of Basidiomycete Polyporus hispidus. hispidin : Fungal metabolite first found in basidiomycete Inonotus hispidus (formerly Polyporus hispidus). | 2.44 | 2 | 0 | 2-pyranones; catechols | antioxidant; EC 2.7.11.13 (protein kinase C) inhibitor; fungal metabolite |
| minocycline hydrochloride [no description available] | 2.44 | 2 | 0 | ||
| demeclocycline hydrochloride demeclocycline hydrochloride : The hydrochloride salt of demeclocycline. A tetracycline antibiotic, it is used (mainly as the hydrochloride) for the treatment of Lyme disease, acne and bronchitis, as well as for hyponatraemia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) where fluid restriction alone has been ineffective. | 2.44 | 2 | 0 | ||
| acyclovir Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.. acyclovir : An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections. | 2.03 | 1 | 0 | 2-aminopurines; oxopurine | antimetabolite; antiviral drug |
| sepiapterin sepiapterin: A substrate of sepiapterin reductase | 2.03 | 1 | 0 | sepiapterin | |
| isoxanthopterin [no description available] | 2.03 | 1 | 0 | dihydroxypteridine | |
| clozapine Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.. clozapine : A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatric disorders like schizophrenia. | 2.44 | 2 | 0 | benzodiazepine; N-arylpiperazine; N-methylpiperazine; organochlorine compound | adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; GABA antagonist; histamine antagonist; muscarinic antagonist; second generation antipsychotic; serotonergic antagonist; xenobiotic |
| ganciclovir [no description available] | 2.03 | 1 | 0 | 2-aminopurines; oxopurine | antiinfective agent; antiviral drug |
| zaprinast zaprinast: anaphylaxis inhibitor; structure | 2.44 | 2 | 0 | triazolopyrimidines | |
| allopurinol Allopurinol: A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.. allopurinol : A bicyclic structure comprising a pyrazole ring fused to a hydroxy-substituted pyrimidine ring. | 2.03 | 1 | 0 | nucleobase analogue; organic heterobicyclic compound | antimetabolite; EC 1.17.3.2 (xanthine oxidase) inhibitor; gout suppressant; radical scavenger |
| thiolactomycin thiolactomycin: from actinomycetes; structure given in first source | 2.03 | 1 | 0 | ||
| 2,4-diaminohypoxanthine 2,4-diaminohypoxanthine: do not confuse abbreviation DAHP with various dehydro-deoxy-arabino-heptulosonic acid phosphates which also use DAHP; RN given refers to parent cpd; structure | 2.03 | 1 | 0 | hydroxypyrimidine | |
| quazinone [no description available] | 2.03 | 1 | 0 | ||
| 8-bromocyclic gmp, sodium salt sodium 8-bromo-3',5'-cyclic GMP : An organic sodium salt having 8-bromoguanosine 3',5'-cyclic phosphate as the counterion. A membrane permeable cGMP analogue that activates protein kinase G (PKG). It is 4.3-fold more potent than cGMP in activating PKG1alpha and promotes relaxation of tracheal and vascular smooth muscle tissue in vitro. | 2.44 | 2 | 0 | organic sodium salt | muscle relaxant; protein kinase G agonist |
| ag-879 AG-879: structure given in first source | 2.44 | 2 | 0 |
| Condition | Indicated | Relationship Strength | Studies | Trials |
|---|---|---|---|---|
| Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. | 0 | 2.44 | 2 | 0 |
| Benign Neoplasms [description not available] | 0 | 2.03 | 1 | 0 |
| Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. | 0 | 2.03 | 1 | 0 |
| Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) | 0 | 2.03 | 1 | 0 |
| Asthma, Bronchial [description not available] | 0 | 2.98 | 4 | 0 |
| Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). | 1 | 4.98 | 4 | 0 |
| Airflow Obstruction, Chronic [description not available] | 0 | 2.77 | 3 | 0 |
| Pulmonary Disease, Chronic Obstructive A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA. | 1 | 4.77 | 3 | 0 |
| Acute Liver Injury, Drug-Induced [description not available] | 0 | 2.06 | 1 | 0 |
| Adverse Drug Event [description not available] | 0 | 2.06 | 1 | 0 |
| Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. | 0 | 2.06 | 1 | 0 |
| Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals. | 0 | 2.06 | 1 | 0 |
| Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. | 0 | 2.5 | 2 | 0 |
| Obstructive Lung Diseases [description not available] | 0 | 2.1 | 1 | 0 |
| Lung Diseases, Obstructive Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent. | 1 | 4.1 | 1 | 0 |
| Idiopathic Parkinson Disease [description not available] | 0 | 2.13 | 1 | 0 |
| Parkinson Disease A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75) | 0 | 2.13 | 1 | 0 |