Page last updated: 2024-11-12

olodaterol

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID11504295
CHEMBL ID605846
CHEBI ID82700
SCHEMBL ID560926
MeSH IDM0546842

Synonyms (53)

Synonym
CHEMBL605846
chebi:82700 ,
olodaterol ,
bi 1744
olodaterol (usan/inn)
striverdi respimat (tn)
868049-49-4
D10145
6-hydroxy-8-((1r)-1-hydroxy-2-((2-(4-methoxyphenyl)-1,1-dimethylethyl)amino)ethyl)-2h-1,4-benzoxazin-3(4h)-one
6-hydroxy-8-(1-hydroxy-2-((2-(4-methoxyphenyl)-1,1-dimethylethyl)amino)ethyl)-2h-1,4-benzoxazin-3(4h)-one
olodaterol [usan:inn]
unii-vd2ysn1afd
vd2ysn1afd ,
2h-1,4-benzoxazin-3(4h)-one, 6-hydroxy-8-((1r)-1-hydroxy-2-((2-(4-methoxyphenyl)- 1,1-dimethylethyl)amino)ethyl)-
S4485
olodaterol [vandf]
olodaterol [mi]
olodaterol [usan]
olodaterol [who-dd]
6-hydroxy-8-((1r)-1-hydroxy-2-((1-(4-methoxyphenyl)-2-methylpropan-2-yl)amino)ethyl)-2h-1,4-benzoxazin-3(4h)-one
olodaterol [inn]
bi-1744
olodaterol hydrochloride [jan]
2h-1,4-benzoxazin-3(4h)-one, 6-hydroxy-8-((1r)-1-hydroxy-2-((2-(4-methoxyphenyl)-1,1-dimethylethyl)amino)ethyl)-
SCHEMBL560926
6-hydroxy-8-[(1r)-1-hydroxy-2-[[2-(4-methoxyphenyl)-1,1-dimethylethyl]amino]ethyl]-2h-1,4-benzoxazin-3(4h)-one
6-hydroxy-8-[(1r)-1-hydroxy-2-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]ethyl]-4h-1,4-benzoxazin-3-one
striverdi
gtpl7543
6-hydroxy-8-[(1r)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl]-2h-1,4-benzoxazin-3(4h)-one
AC-29048
DB09080
AKOS026674098
(r)-6-hydroxy-8-(1-hydroxy-2-((1-(4-methoxyphenyl)-2-methylpropan-2-yl)amino)ethyl)-2h-benzo[b][1,4]oxazin-3(4h)-one
6-hydroxy-8-[(1r)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino}ethyl]-3,4-dihydro-2h-1,4-benzoxazin-3-one
AS-74944
EX-A1729
HY-14301
CS-6275
olodaterol free base
868049-49-4 (free base)
bi1744
BCP11473
Q7088466
AMY16614
NCGC00522533-01
C76830
olodaterol (bi 1744)
DTXSID601024792
EN300-20331067
olodaterolum
r03ac19
bdbm50569861

Research Excerpts

Overview

Olodaterol is a novel long-acting β2-agonist with a 24-hour bronchodilator profile. It has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life.

ExcerptReferenceRelevance
"Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile. "( Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2-4 COPD: results from two replicate 48-week studies.
Allen, L; Feldman, GJ; Ferguson, GT; Hamilton, A; Hofbauer, P; Korducki, L; Sachs, P, 2014
)
2.16
"Olodaterol is a novel long-acting β2-agonist (LABA) with ≥24-h duration of action in preclinical and clinical studies."( A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting β2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease.
Beck, E; Fogarty, C; Hamilton, AL; Koker, P; Korducki, L; Maleki-Yazdi, MR, 2015
)
2.08
"Olodaterol is a novel, inhaled long-acting β2-agonist (LABA) with >24-hour duration of action investigated in asthma and chronic obstructive pulmonary disease."( Dose-finding evaluation of once-daily treatment with olodaterol, a novel long-acting β2-agonist, in patients with asthma: results of a parallel-group study and a crossover study.
Beck, E; Beeh, KM; Blahova, Z; D'Urzo, T; Fležar, M; Gahlemann, M; Hart, L; O'Byrne, PM; Toorawa, R, 2015
)
2.11
"Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies."( Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease.
Fukuchi, Y; Hamilton, AL; Ichinose, M; Izumoto, T; Kunz, C; Tadayasu, Y; Takizawa, A, 2015
)
2.11
"Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile."( Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.
Al Assir, SA; El Khoury, GM; Kabbara, WK; Ramadan, WH, 2015
)
1.4
"Olodaterol is a new very-long-acting β2-agonist that has been shown, in controlled trials, to improve lung function as well as clinical outcomes and quality of life."( Striving for optimal bronchodilation: focus on olodaterol.
Incorvaia, C; Makri, E; Montagni, M; Riario-Sforza, GG; Ridolo, E, 2016
)
1.41
"Olodaterol is an orally inhaled β2 -agonist for treatment of chronic obstructive pulmonary disease (COPD). "( Model-based evaluation of pulmonary pharmacokinetics in asthmatic and COPD patients after oral olodaterol inhalation.
Borghardt, JM; Kloft, C; Kunz, C; Staab, A; Weber, B, 2016
)
2.1
"Olodaterol is a novel inhaled long-acting β"( The impact of olodaterol on the risk of mortality and serious adverse events: a systematic review and meta-analysis.
Kim, HJ; Lee, CH; Lee, HW, 2017
)
2.26
"Olodaterol is a novel long-acting β(2)-adrenoceptor agonist with a pre-clinical profile that suggests 24-h bronchodilation may be achieved with once-daily administration."( 24-hour bronchodilation following a single dose of the novel β(2)-agonist olodaterol in COPD.
Cornelissen, PJ; Drenth, BM; Hamilton, AL; Pivovarova, A; Rascher, J; Smeets, JJ; van Noord, JA, 2011
)
1.32
"Olodaterol appears to be a promising long-acting β(2)-adrenoceptor agonist,with bronchodilation maintained over 24 h that offers an opportunity for once-daily dosing in patients who require maintenance bronchodilator therapy for the management of COPD symptoms."( 24-hour bronchodilation following a single dose of the novel β(2)-agonist olodaterol in COPD.
Cornelissen, PJ; Drenth, BM; Hamilton, AL; Pivovarova, A; Rascher, J; Smeets, JJ; van Noord, JA, 2011
)
2.04

Effects

ExcerptReferenceRelevance
"Olodaterol has a rapid onset of action (comparable to formoterol) and provides bronchodilation over 24 hours."( Striving for optimal bronchodilation: focus on olodaterol.
Incorvaia, C; Makri, E; Montagni, M; Riario-Sforza, GG; Ridolo, E, 2016
)
1.41

Treatment

Treatment with olodaterol or formoterol is not associated with arrhythmias or a persistent increase in heart rate as assessed by Holter ECG in patients with COPD. All olodeterol treatments demonstrated statistically significant improvements in FEV1 AUC0-24 response at 3 weeks versus placebo.

ExcerptReferenceRelevance
"All olodaterol treatments demonstrated statistically significant improvements in FEV1 AUC0-24 response at 3 weeks versus placebo (p < 0.0001); adjusted mean treatment difference versus placebo was 0.191 L for olodaterol 2.5 μg BID (95 % confidence interval [CI] 0.152, 0.229), 0.150 L for 5 μg QD (95 % CI 0.111, 0.189), 0.228 L for 5 μg BID (95 % CI 0.190, 0.266) and 0.209 L for 10 μg QD (95 % CI 0.170, 0.247)."( Randomised, double-blind, placebo-controlled crossover study to investigate different dosing regimens of olodaterol delivered via Respimat® in patients with moderate to severe persistent asthma.
Beeh, KM; Fležar, M; Gahlemann, M; LaForce, C; Toorawa, R; Wenz, A, 2015
)
1.11
"Treatment with olodaterol or formoterol is not associated with arrhythmias or a persistent increase in heart rate as assessed by Holter ECG in patients with COPD."( A Post Hoc Holter ECG Analysis of Olodaterol and Formoterol in Moderate-to-Very-Severe COPD.
Alter, P; Andreas, S; Bothner, U; de la Hoz, A; Kloer, I; Trampisch, M, 2020
)
1.19

Toxicity

Randomized controlled trials comparing olodaterol with placebo for patients with COPD or asthma were included. We could not find any relationship between inhaled olodlerol use and nonfatal serious adverse events.

ExcerptReferenceRelevance
"05, post hoc) at week 12, with an incidence of adverse events comparable with that of placebo."( Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2-4 COPD: results from two replicate 48-week studies.
Allen, L; Feldman, GJ; Ferguson, GT; Hamilton, A; Hofbauer, P; Korducki, L; Sachs, P, 2014
)
0.71
" Pre-specified analyses of pooled data assessed the adverse events (AEs) and serious AEs in the whole population, and in subgroups with cardiac disease, along with in-depth electrocardiogram and Holter monitoring."( One-Year Safety of Olodaterol Once Daily via Respimat® in Patients with GOLD 2-4 Chronic Obstructive Pulmonary Disease: Results of a Pre-Specified Pooled Analysis.
Bothner, U; Ferguson, GT; Hamilton, A; Koch, A; Korducki, L; Magder, S; McGarvey, L; Niewoehner, D; Sachs, P; Tetzlaff, K; Vogelmeier, C, 2015
)
0.75
"Randomized controlled trials comparing olodaterol with placebo for patients with COPD or asthma, which evaluated mortality or serious adverse events, were included."( The impact of olodaterol on the risk of mortality and serious adverse events: a systematic review and meta-analysis.
Kim, HJ; Lee, CH; Lee, HW, 2017
)
1.09
" We could not find any relationship between inhaled olodaterol use and nonfatal serious adverse events."( The impact of olodaterol on the risk of mortality and serious adverse events: a systematic review and meta-analysis.
Kim, HJ; Lee, CH; Lee, HW, 2017
)
1.07
" There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment."( Long-term safety of tiotropium/olodaterol Respimat
Bothner, U; Buhl, R; Derom, E; Kloer, IM; LaForce, C; Trampisch, M, 2018
)
0.77

Pharmacokinetics

ExcerptReferenceRelevance
" The aim of the present study was to describe the plasma and urine pharmacokinetics of olodaterol after intravenous administration and oral inhalation in healthy volunteers by population pharmacokinetic modelling and thereby to infer its pulmonary fate."( Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.
Borghardt, JM; Formella, S; Kloft, C; Kunz, C; Staab, A; Weber, B, 2016
)
0.89
" A stepwise model building approach was applied, using population pharmacokinetic modelling."( Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.
Borghardt, JM; Formella, S; Kloft, C; Kunz, C; Staab, A; Weber, B, 2016
)
0.67
"A pharmacokinetic model, including three depot compartments with associated parallel first-order absorption processes (pulmonary model) on top of a four-compartment body model (systemic disposition model), was found to describe the data the best."( Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach.
Borghardt, JM; Formella, S; Kloft, C; Kunz, C; Staab, A; Weber, B, 2016
)
0.67
" The aims of this population pharmacokinetic (PK) analysis were: (1) to investigate systemic PK and thereby make inferences about pulmonary PK in asthmatic patients, COPD patients and healthy volunteers, and (2) to assess whether differences in pulmonary efficacy might be expected based on pulmonary PK characteristics."( Model-based evaluation of pulmonary pharmacokinetics in asthmatic and COPD patients after oral olodaterol inhalation.
Borghardt, JM; Kloft, C; Kunz, C; Staab, A; Weber, B, 2016
)
0.65
"8%) of PBIO was slowly absorbed with an absorption half-life of 18."( Model-based evaluation of pulmonary pharmacokinetics in asthmatic and COPD patients after oral olodaterol inhalation.
Borghardt, JM; Kloft, C; Kunz, C; Staab, A; Weber, B, 2016
)
0.65
"This single site, open-label, phase Ib clinical study assessed the pharmacokinetic (PK) and safety profiles of once-daily Tio + Olo FDC (5 μg/5 μg) after single dose and at steady state in Chinese patients with moderate to severe COPD over 3 weeks."( Pharmacokinetics and safety of tiotropium+olodaterol 5 μg/5 μg fixed-dose combination in Chinese patients with COPD.
Hu, C; Hu, N; Luo, Z; Shu, S; Tadayasu, Y; Wang, Z, 2020
)
0.82

Compound-Compound Interactions

ExcerptReferenceRelevance
" Subjects received single doses of 20 or 30 μg olodaterol administered with the Respimat Soft Mist inhaler."( Pharmacokinetics and safety of olodaterol administered with the Respimat Soft Mist inhaler in subjects with impaired hepatic or renal function.
Formella, S; Halabi, A; Hamilton, A; Kunz, C; Luedtke, D; Unseld, A; Wein, M, 2016
)
0.98

Dosage Studied

Olodaterol appears to be a promising long-acting β(2)-adrenoceptor agonist. It offers an opportunity for once-daily dosing in patients who require maintenance bronchodilator therapy. A clear dose-response relationship was demonstrated regarding pulmo.

ExcerptRelevanceReference
" In summary, the preclinical profile of compound (R)-4p (olodaterol, also known as BI 1744 CL) suggests a potential for once-daily dosing in man accompanied with an improved safety profile."( Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
Bouyssou, T; Büttner, FH; Heine, C; Hoenke, C; Konetzki, I; Lotz, R; Lustenberger, P; Pestel, S; Rudolf, K; Schnapp, A; Sieger, P, 2010
)
0.98
" Taken together, the preclinical behavior of olodaterol suggests that this novel beta(2)-AR agonist has the profile for once-daily dosing in humans concomitant with a fast onset of action and a favorable systemic pharmacodynamic profile."( Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models.
Bouyssou, T; Casarosa, P; Devillier, P; Konetzki, I; Naline, E; Pestel, S; Schnapp, A, 2010
)
0.9
"A single-center, double-blind, placebo-controlled, 5-way crossover study including 24-h spirometry (FEV(1), FVC), safety, tolerability and pharmacokinetics (in a subset of patients) following dosing of olodaterol 2 μg, 5 μg, 10 μg and 20 μg; the washout period between test-days was at least 14 days."( 24-hour bronchodilation following a single dose of the novel β(2)-agonist olodaterol in COPD.
Cornelissen, PJ; Drenth, BM; Hamilton, AL; Pivovarova, A; Rascher, J; Smeets, JJ; van Noord, JA, 2011
)
0.79
"Olodaterol appears to be a promising long-acting β(2)-adrenoceptor agonist,with bronchodilation maintained over 24 h that offers an opportunity for once-daily dosing in patients who require maintenance bronchodilator therapy for the management of COPD symptoms."( 24-hour bronchodilation following a single dose of the novel β(2)-agonist olodaterol in COPD.
Cornelissen, PJ; Drenth, BM; Hamilton, AL; Pivovarova, A; Rascher, J; Smeets, JJ; van Noord, JA, 2011
)
2.04
" In these studies, once-daily olodaterol improved lung function relative to placebo over 48 weeks of treatment, with such improvements being achieved and maintained within the 24-h dosage interval, supporting its once-daily administration."( Olodaterol: a review of its use in chronic obstructive pulmonary disease.
Deeks, ED, 2015
)
2.15
"This randomised, double-blind, four-way, crossover, Phase II study compared the 24-h forced expiratory volume in 1 s (FEV1) profile of alternative dosing frequencies of two total daily doses of olodaterol (5 and 10 μg) in patients with chronic obstructive pulmonary disease (COPD)."( A randomised, double-blind, four-way, crossover trial comparing the 24-h FEV1 profile for once-daily versus twice-daily treatment with olodaterol, a novel long-acting β2-agonist, in patients with chronic obstructive pulmonary disease.
Aalbers, R; Aumann, JL; Coeck, C; Hamilton, AL; Joos, GF; Korducki, L; Kunz, C, 2015
)
0.81
" Furthermore, the in vivo data suggest that the anti-inflammatory properties of olodaterol are maintained after repeated dosing for 4 days."( The long-acting β2 -adrenoceptor agonist olodaterol attenuates pulmonary inflammation.
Devillier, P; Duechs, MJ; Kollak, I; Naline, E; Wex, E; Wollin, L, 2015
)
0.91
" A clear dose-response relationship was demonstrated regarding pulmonary function; the two highest olodaterol doses (10 and 20 μg) formed the plateau of the dose-response curve."( A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting β2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease.
Beck, E; Fogarty, C; Hamilton, AL; Koker, P; Korducki, L; Maleki-Yazdi, MR, 2015
)
0.85
" These once-daily dosing inhalers are anticipated to impact favorably on patient preference and compliance."( Profile of a fixed-dose combination of tiotropium/olodaterol and its potential in the treatment of COPD.
Jayaram, L; Muruganandan, S, 2015
)
0.67
" Further studies are necessary to confirm the optimum dosing regimen in asthma."( Randomised, double-blind, placebo-controlled crossover study to investigate different dosing regimens of olodaterol delivered via Respimat® in patients with moderate to severe persistent asthma.
Beeh, KM; Fležar, M; Gahlemann, M; LaForce, C; Toorawa, R; Wenz, A, 2015
)
0.63
" PFTs were performed over a 24-hour dosing interval after 4 weeks; primary end point was FEV1 area under the curve from 0-24 hours (AUC0-24) response (change from study baseline [mean FEV1] after 4 weeks)."( Dose-finding evaluation of once-daily treatment with olodaterol, a novel long-acting β2-agonist, in patients with asthma: results of a parallel-group study and a crossover study.
Beck, E; Beeh, KM; Blahova, Z; D'Urzo, T; Fležar, M; Gahlemann, M; Hart, L; O'Byrne, PM; Toorawa, R, 2015
)
0.67
" A clear dose-response relationship was observed across all treatment groups."( Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease.
Fukuchi, Y; Hamilton, AL; Ichinose, M; Izumoto, T; Kunz, C; Tadayasu, Y; Takizawa, A, 2015
)
0.67
" Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects."( Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.
Al Assir, SA; El Khoury, GM; Kabbara, WK; Ramadan, WH, 2015
)
0.68
" Other clinical trials demonstrated that olodaterol produced beneficial effects on FEV1 measures throughout the 24-hour dosing interval."( Olodaterol for the treatment of chronic obstructive pulmonary disease.
Abilmona, RM; Kabbara, WK; Ramadan, WH, 2016
)
2.14
" Changes in heart rate and systolic/diastolic BP were measured before and after dosing with the study medication at each visit."( Effect of long-acting β
Alter, P; Andreas, S; Bothner, U; Buhl, R; Haensel, M; Trampisch, M, 2018
)
0.48
" Olodaterol and indacaterol are administered once-daily and may offer an adherence advantage over other LABAs with more frequent dosing schedules."( Olodaterol for the treatment of chronic obstructive pulmonary disease: a narrative review.
Melani, AS, 2018
)
2.83
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
beta-adrenergic agonistAn agent that selectively binds to and activates beta-adrenergic receptors.
bronchodilator agentAn agent that causes an increase in the expansion of a bronchus or bronchial tubes.
[role 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]

Drug Classes (5)

ClassDescription
benzoxazine
phenolsOrganic aromatic compounds having one or more hydroxy groups attached to a benzene or other arene ring.
aromatic etherAny ether in which the oxygen is attached to at least one aryl substituent.
secondary alcoholA 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.
secondary amino compoundA compound formally derived from ammonia by replacing two hydrogen atoms by organyl groups.
[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 Targets (2)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Beta-2 adrenergic receptorHomo sapiens (human)EC50 (µMol)0.00010.00000.311110.0000AID1760531; AID1783430
Beta-1 adrenergic receptorHomo sapiens (human)EC50 (µMol)0.12300.00010.49146.0000AID1783429
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (37)

Processvia Protein(s)Taxonomy
diet induced thermogenesisBeta-2 adrenergic receptorHomo sapiens (human)
regulation of sodium ion transportBeta-2 adrenergic receptorHomo sapiens (human)
transcription by RNA polymerase IIBeta-2 adrenergic receptorHomo sapiens (human)
receptor-mediated endocytosisBeta-2 adrenergic receptorHomo sapiens (human)
smooth muscle contractionBeta-2 adrenergic receptorHomo sapiens (human)
cell surface receptor signaling pathwayBeta-2 adrenergic receptorHomo sapiens (human)
activation of transmembrane receptor protein tyrosine kinase activityBeta-2 adrenergic receptorHomo sapiens (human)
adenylate cyclase-modulating G protein-coupled receptor signaling pathwayBeta-2 adrenergic receptorHomo sapiens (human)
endosome to lysosome transportBeta-2 adrenergic receptorHomo sapiens (human)
response to coldBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of protein kinase A signalingBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of bone mineralizationBeta-2 adrenergic receptorHomo sapiens (human)
heat generationBeta-2 adrenergic receptorHomo sapiens (human)
negative regulation of multicellular organism growthBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of MAPK cascadeBeta-2 adrenergic receptorHomo sapiens (human)
bone resorptionBeta-2 adrenergic receptorHomo sapiens (human)
negative regulation of G protein-coupled receptor signaling pathwayBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIBeta-2 adrenergic receptorHomo sapiens (human)
negative regulation of smooth muscle contractionBeta-2 adrenergic receptorHomo sapiens (human)
brown fat cell differentiationBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of mini excitatory postsynaptic potentialBeta-2 adrenergic receptorHomo sapiens (human)
adrenergic receptor signaling pathwayBeta-2 adrenergic receptorHomo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathwayBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of protein serine/threonine kinase activityBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of cold-induced thermogenesisBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of autophagosome maturationBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of lipophagyBeta-2 adrenergic receptorHomo sapiens (human)
cellular response to amyloid-betaBeta-2 adrenergic receptorHomo sapiens (human)
response to psychosocial stressBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of cAMP-dependent protein kinase activityBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of AMPA receptor activityBeta-2 adrenergic receptorHomo sapiens (human)
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressureBeta-2 adrenergic receptorHomo sapiens (human)
positive regulation of heart rate by epinephrine-norepinephrineBeta-1 adrenergic receptorHomo sapiens (human)
positive regulation of the force of heart contraction by epinephrine-norepinephrineBeta-1 adrenergic receptorHomo sapiens (human)
diet induced thermogenesisBeta-1 adrenergic receptorHomo sapiens (human)
response to coldBeta-1 adrenergic receptorHomo sapiens (human)
heat generationBeta-1 adrenergic receptorHomo sapiens (human)
negative regulation of multicellular organism growthBeta-1 adrenergic receptorHomo sapiens (human)
fear responseBeta-1 adrenergic receptorHomo sapiens (human)
regulation of circadian sleep/wake cycle, sleepBeta-1 adrenergic receptorHomo sapiens (human)
brown fat cell differentiationBeta-1 adrenergic receptorHomo sapiens (human)
regulation of postsynaptic membrane potentialBeta-1 adrenergic receptorHomo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathwayBeta-1 adrenergic receptorHomo sapiens (human)
positive regulation of cold-induced thermogenesisBeta-1 adrenergic receptorHomo sapiens (human)
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressureBeta-1 adrenergic receptorHomo sapiens (human)
positive regulation of MAPK cascadeBeta-1 adrenergic receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (15)

Processvia Protein(s)Taxonomy
amyloid-beta bindingBeta-2 adrenergic receptorHomo sapiens (human)
beta2-adrenergic receptor activityBeta-2 adrenergic receptorHomo sapiens (human)
protein bindingBeta-2 adrenergic receptorHomo sapiens (human)
adenylate cyclase bindingBeta-2 adrenergic receptorHomo sapiens (human)
potassium channel regulator activityBeta-2 adrenergic receptorHomo sapiens (human)
identical protein bindingBeta-2 adrenergic receptorHomo sapiens (human)
protein homodimerization activityBeta-2 adrenergic receptorHomo sapiens (human)
protein-containing complex bindingBeta-2 adrenergic receptorHomo sapiens (human)
norepinephrine bindingBeta-2 adrenergic receptorHomo sapiens (human)
beta-adrenergic receptor activityBeta-1 adrenergic receptorHomo sapiens (human)
beta1-adrenergic receptor activityBeta-1 adrenergic receptorHomo sapiens (human)
protein bindingBeta-1 adrenergic receptorHomo sapiens (human)
PDZ domain bindingBeta-1 adrenergic receptorHomo sapiens (human)
alpha-2A adrenergic receptor bindingBeta-1 adrenergic receptorHomo sapiens (human)
protein heterodimerization activityBeta-1 adrenergic receptorHomo sapiens (human)
G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potentialBeta-1 adrenergic receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
nucleusBeta-2 adrenergic receptorHomo sapiens (human)
lysosomeBeta-2 adrenergic receptorHomo sapiens (human)
endosomeBeta-2 adrenergic receptorHomo sapiens (human)
early endosomeBeta-2 adrenergic receptorHomo sapiens (human)
Golgi apparatusBeta-2 adrenergic receptorHomo sapiens (human)
plasma membraneBeta-2 adrenergic receptorHomo sapiens (human)
endosome membraneBeta-2 adrenergic receptorHomo sapiens (human)
membraneBeta-2 adrenergic receptorHomo sapiens (human)
apical plasma membraneBeta-2 adrenergic receptorHomo sapiens (human)
clathrin-coated endocytic vesicle membraneBeta-2 adrenergic receptorHomo sapiens (human)
neuronal dense core vesicleBeta-2 adrenergic receptorHomo sapiens (human)
receptor complexBeta-2 adrenergic receptorHomo sapiens (human)
plasma membraneBeta-2 adrenergic receptorHomo sapiens (human)
early endosomeBeta-1 adrenergic receptorHomo sapiens (human)
plasma membraneBeta-1 adrenergic receptorHomo sapiens (human)
Schaffer collateral - CA1 synapseBeta-1 adrenergic receptorHomo sapiens (human)
neuronal dense core vesicleBeta-1 adrenergic receptorHomo sapiens (human)
plasma membraneBeta-1 adrenergic receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (19)

Assay IDTitleYearJournalArticle
AID1783428Selectivity ratio of EC50 for agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells to EC50 for agonist activity at human beta1 adrenoreceptor overexpressed in HEK293 cells2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID457589Apparent permeability from basolateral to apical side in human Caco-2 cells2010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID457248Apparent permeability from apical to basolateral side in human Caco-2 cells2010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID1783425Myorelaxant effect in guinea pig model of histamine-induced smooth muscle contraction assessed as time duration of action measured over 12 hrs2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID1783429Agonist activity at human beta1 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID1760530Agonist activity at beta1 adrenoceptor in electrically stimulated Dunkin Hartley guinea pig left atria assessed as induction of isoprenaline-induced contraction incubated for 10 to 15 mins by alphascreen technology2020Journal of medicinal chemistry, 12-24, Volume: 63, Issue:24
Recent Advances in β
AID1783426Myorelaxant effect in guinea pig model of histamine-induced smooth muscle contraction assessed as time of onset of action measured over 12 hrs2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID1783423In vivo agonist activity at beta2 adrenergic receptor isolated from guinea pig tracheal smooth muscle assessed as inhibition of histamine-induced tracheal smooth muscle contraction by measuring maximal relaxant effect relative to control2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID457250Clearance in human hepatocytes2010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID1783424In vivo agonist activity at beta2 adrenergic receptor isolated from guinea pig tracheal smooth muscle assessed as inhibition of histamine-induced tracheal smooth muscle contraction2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID1760549Inhibition of acetylcholine-induced bronchoconstriction in guinea pig assessed as duration of action by measuring half life2020Journal of medicinal chemistry, 12-24, Volume: 63, Issue:24
Recent Advances in β
AID1783427Agonist activity at human beta2 adrenoreceptor in HEK293 cells assessed as cAMP accumulation by measuring intrinsic activity relative to control2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID1783430Agonist activity at human beta2 adrenoreceptor overexpressed in HEK293 cells assessed as cAMP accumulation2021European journal of medicinal chemistry, Nov-15, Volume: 2248-Hydroxyquinolin-2(1H)-one analogues as potential β
AID457588Bronchoprotection in intratracheally dosed guinea pig Konzett-Roessler model assessed as inhibition of acetylcholine-induced increase in pulmonary resistance administered after 3 acetylcholine challenges every 10 mins for 5 hrs2010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID457249Clearance in rat hepatocytes2010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID457590Oral bioavailability in rat2010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID1760531Agonist activity at beta2 adrenoceptor (unknown origin)2020Journal of medicinal chemistry, 12-24, Volume: 63, Issue:24
Recent Advances in β
AID457587Lipophilicity, log D at pH 7.42010Bioorganic & medicinal chemistry letters, Feb-15, Volume: 20, Issue:4
Discovery of olodaterol, a novel inhaled beta2-adrenoceptor agonist with a 24 h bronchodilatory efficacy.
AID1346250Human beta2-adrenoceptor (Adrenoceptors)2010The Journal of pharmacology and experimental therapeutics, Jul, Volume: 334, Issue:1
Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (93)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's71 (76.34)24.3611
2020's22 (23.66)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 79.78

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.

MetricThis Compound (vs All)
Research Demand Index79.78 (24.57)
Research Supply Index4.93 (2.92)
Research Growth Index6.86 (4.65)
Search Engine Demand Index134.22 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (79.78)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials37 (37.00%)5.53%
Reviews22 (22.00%)6.00%
Case Studies1 (1.00%)4.05%
Observational1 (1.00%)0.25%
Other39 (39.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (80)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Regulatory Required Non Interventional Study to Monitor the Safety and Effectiveness of Once Daily Treatment of Orally Inhaled Vahelva Respimat (Tiotropium + Olodaterol Fixed Dose Combination 2.5µg/2.5µg Per Puff (2 Puffs Comprise One Medicinal Dose)) f [NCT02864407]3,223 participants (Actual)Observational2016-12-19Completed
A Phase II, Randomized, Double Blind, Placebo Controlled, Three-way Crossover Study to Assess the Bronchodilator Effect of RPL554 Administered in Addition to Open Label Tiotropium/Olodaterol in Patients With COPD [NCT03673670]Phase 279 participants (Actual)Interventional2018-07-16Completed
Early Intervention Effectiveness of Tiotropium / Olodaterol Compared to Tiotropium in COPD [NCT04249310]6,788 participants (Actual)Observational2020-03-27Completed
A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses (2.5 μg, 5 μg, 10 μg, 20 μg and 40 μg) of BI 1744 CL (Administered With the Respimat®) in Free Dos [NCT02259946]Phase 148 participants (Actual)Interventional2006-04-30Completed
A Randomized, Double-blind, Double-dummy, Active-controlled, Multi-center, Parallel Group Study to Show the Superiority in Lung Function of 12 Weeks Once Daily Treatment With Orally Inhaled Tiotropium+Olodaterol Fixed Dose Combination Delivered by the Res [NCT03240575]Phase 4302 participants (Actual)Interventional2017-08-14Completed
Comparison of 1-year Treatment With Inhaled Long Acting Bronchodilators (LABD) Plus Inhaled Glucocorticosteroids (ICS) Versus LABD Without ICS on Re-hospitalizations and/or Death in Elderly Patients With Chronic Obstructive Pulmonary Disease (COPD) Recent [NCT03662711]Phase 4843 participants (Actual)Interventional2018-11-11Terminated(stopped due to Contract terminated between AIFA and the Sponsor (University of Ferrara))
Quality of Life and Preference of COPD Patients After Switching From Tiotropium Monotherapy (Spiriva® Handihaler®) to Dual Therapy With Tiotropium Bromide Plus Olodaterol (Spiolto® Respimat®) Under Real Life Conditions in Greece (ELLACTO II Study) [NCT04672941]1,396 participants (Actual)Observational2021-02-16Completed
Taiwan Outcomes and Real-world Treatment Options for Chronic Obstructive Pulmonary Disease [NCT04011475]1,617 participants (Actual)Observational2019-12-29Completed
A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses (0.5 μg to 70 μg Administered With the Respimat®) of BI 1744 CL in Healthy Male and Female Volunte [NCT02171780]Phase 1122 participants (Actual)Interventional2005-02-28Completed
A Randomised, Single-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Peroral Doses (15, 30, 40 μg Free Cation) BI 1744 CL in Healthy Male Volunteers [NCT02171793]Phase 124 participants (Actual)Interventional2007-06-30Completed
A Double-blind, Randomised, Placebo Controlled (Within a Dose Group) Study to Evaluate Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses (5 μg, 10 μg and 20 μg) of BI 1744 CL for 14 Days in Healthy Male Volunteers [NCT02172105]Phase 136 participants (Actual)Interventional2008-01-31Completed
Comparison of Exacerbation Risk and Health Outcomes in Maintenance Treatment naïve Chronic Obstructive Pulmonary Disease (COPD) Patients Using Stiolto Versus Trelegy, a Real-World Study [NCT05169424]9,117 participants (Actual)Observational2021-12-17Completed
A Randomised, Double-blind, Cross-over Study to Evaluate the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (5/5 µg) Compared With Tiotropium (5 µg), Both Delivered by the Respimat® Inhaler, on Breathlessness [NCT02853123]Phase 4106 participants (Actual)Interventional2016-09-22Completed
Pharmacokinetics, Safety and Tolerability of a Single Dose of BI 1744 CL (20 μg Administered With the Respimat® Inhaler) in Patients With Mild and Moderate Hepatic Impairment (Child Pugh Classifications A and B) in Comparison to a Single Dose of BI 1744 C [NCT02171832]Phase 132 participants (Actual)Interventional2009-07-31Completed
A Double-blind, Randomised, Placebo Controlled, Six-way Crossover Study Including an Open-label Positive Control (Moxifloxacin) to Assess the Influence of Via Respimat® Inhaled BI 1744 CL (Single Doses of 10 μg, 20 μg, 30 μg and 50 μg) on the QT/QTc Inter [NCT02172144]Phase 124 participants (Actual)Interventional2007-06-30Completed
A Single-blind, Randomised, Two-way Crossover Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of the Fixed Dose Combination of BI 1744 CL Plus BI 54903 XX Via Respimat® B Versus the Free Combination of BI 1744 CL Via Respimat® A and BI 5 [NCT02220660]Phase 132 participants (Actual)Interventional2009-03-31Completed
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (2.5 μg, 10 μg, and 30 μg) of BI 1744 CL for 14 Days in Healthy Male and Female Volunteers (Doubleblind, Randomised, Placebo Controlled [at Each Dose Level] St [NCT02171806]Phase 147 participants (Actual)Interventional2006-01-31Completed
An Open Label, Randomised, Three-way Crossover Phase I Study to Assess Safety, Tolerability and Pharmacokinetics of the Fixed Dose Combination of BI 1744 CL Plus BI 54903 XX Via Respimat® B Versus the Mono Products of BI 1744 CL Via Respimat® A and BI 549 [NCT02222428]Phase 136 participants Interventional2009-04-30Completed
Health Care Resource Utilization, Cost and Other Outcomes of Patients Diagnosed With COPD Initiating Tiotropium Bromide/Olodaterol Versus Fluticasone Furoate/Umeclidinium/Vilanterol [NCT05127304]11,316 participants (Actual)Observational2021-02-26Completed
Safety Profile of Tiotropium + Olodaterol Used as Maintenance Treatment in COPD Patients in Taiwan: a Non-interventional Study Based on the Taiwan National Health Insurance (NHI) Data [NCT05393245]19,467 participants (Actual)Observational2022-09-30Completed
An Exploratory, Randomised, Double-blind, Double-dummy, Active-controlled, Two Period Cross-over Study to Investigate the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (FDC) Delivered by the Respimat® Inhaler [NCT03055988]Phase 476 participants (Actual)Interventional2017-03-29Completed
Randomised, Double-Blind, Placebo-Controlled, 5-Way Cross-Over Study to Assess the Efficacy (Bronchoprotection) and Safety of a Single Dose of Orally Inhaled BI 1744 CL (2, 5, 10 and 20ug) in Patients With Intermittent Asthma [NCT00928668]Phase 232 participants (Actual)Interventional2006-01-31Completed
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 2198 participants (Actual)Interventional2010-02-28Completed
Safety, Tolerability and Pharmacokinetics of Single Rising Doses of 0.5 μg, 2.5 μg, 5 μg, 10 μg, 15 μg, 20 μg, 25 μg and 30 μg BI 1744 CL (Calculated as Free Base) Given as Intravenous Infusion Over 30 Minutes to Healthy Male Subjects. A Single-centre, Si [NCT02172131]Phase 164 participants (Actual)Interventional2006-10-31Terminated
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (2 μg/5 μg, 10 μg/5 μg, and 40 μg/10 μg) of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide for 14 Days in Healthy Male Volunteers (Double-blind, [NCT02259959]Phase 136 participants (Actual)Interventional2007-04-30Completed
Investigation of the Metabolism and Pharmacokinetics of 20 μg (Calculated as Free Base) [14C]BI 1744 CL Administered as a 3-hour Infusion and 40 μg (Calculated as Free Base) [14C]BI 1744 CL Administered as an Oral Solution. [NCT02172157]Phase 111 participants (Actual)Interventional2008-02-29Completed
Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy (Bronchodilation) and Safety of 4 Weeks of Treatment of Orally Inhaled BI 1744 CL (4 Doses) Delivered by the Respimat® Inhaler in Patients With Asthma [NCT00467740]Phase 2296 participants (Actual)Interventional2007-05-31Completed
A Randomised, Double-blind, Active-controlled Parallel Group Study to Evaluate the Effect of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination Compared With Tiotropium on Chronic Obstructive Pulmonary Diseas [NCT02296138]Phase 37,903 participants (Actual)Interventional2015-01-13Completed
Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Treatment of Orally Inhaled BI 1744 CL (3 - 4 Doses) Delivered by the Respimat® Inhaler in Patients With COPD [NCT00452400]Phase 2409 participants (Actual)Interventional2007-03-31Completed
Randomised, Double-Blind, Cross-over Study to Determine the 24-hour FEV1-time Profile of Orally Inhaled BI 1744 CL, Delivered With the Respimat Inhaler, After 3 Weeks of Once Daily or Twice Daily Administration in Patients With Chronic Obstructive Pulmona [NCT00846768]Phase 247 participants (Actual)Interventional2009-02-28Completed
Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL Delivered by the Respimat Inhaler in Japanese Patients With COPD [NCT00824382]Phase 2328 participants (Actual)Interventional2009-01-31Completed
Randomised, Double-blind, 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 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Res [NCT00782210]Phase 3625 participants (Actual)Interventional2008-11-30Completed
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 3937 participants (Actual)Interventional2009-01-31Completed
Randomised, Double-blind, Placebo-controlled, 3-way Cross-over Study to Determine the Effect of Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 µg] and 10 µg [2 Actuations of 5 µg]) Delivered by the Respimat® Inhaler on Exercise Enduranc [NCT01040130]Phase 3151 participants (Actual)Interventional2010-01-31Completed
Randomised, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 3 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination With 5 Microgram Tiotropium Bromide (Delivered by the Respimat Inha [NCT00696020]Phase 2360 participants (Actual)Interventional2008-06-30Completed
Characterization of 24 Hour Spirometry Profiles of Inhaled BI 1744 CL and Inhaled Foradil in Patients With Chronic Obstructive Pulmonary Disease [NCT00932646]Phase 3100 participants (Actual)Interventional2009-06-30Completed
Randomised, Double-blind, 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 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Res [NCT00782509]Phase 3644 participants (Actual)Interventional2009-02-28Completed
Randomised, Double-blind, Cross-over Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 2 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination (FDC) With 5 Microgram Tiotropium Bromide (Delivered by the Respimat® I [NCT00720499]Phase 2141 participants (Actual)Interventional2008-07-31Completed
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 3906 participants (Actual)Interventional2009-02-28Completed
Comparison of Bronchodilation and Oxygenation Patterns Induced by Long-acting β2-agonists and Muscarinic Antagonists in Chronic Obstructive Pulmonary Disease (COPD) [NCT05927155]Phase 330 participants (Actual)Interventional2021-06-15Completed
Effects of Ultra-long Acting Bronchodilator Therapy Assessed by Impulse Oscillometry in Smoking Asthmatics Taking Inhaled Corticosteroids [NCT02682862]Phase 417 participants (Actual)Interventional2016-07-11Completed
A Randomized, Crossover, Placebo Controlled, Double-blind Trial of the Effect of STIOLTO™ RESPIMAT® on Central and Peripheral Components of Fatigue During Exercise in Chronic Obstructive Pulmonary Disease [NCT02845752]Phase 414 participants (Actual)Interventional2017-03-01Completed
Randomised, Double-blind, Placebo-controlled, 3-way Cross-over Study to Determine the Effect of Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 µg] and 10 µg [2 Actuations of 5 µg]) Delivered by the Respimat® Inhaler on Exercise Enduranc [NCT01040793]Phase 3157 participants (Actual)Interventional2010-01-31Completed
A Randomised, Double-blind, 8 Treatments, 4 Periods, Incomplete Crossover Study to Determine the Optimal Free Dose Combination of BI 1744 CL and Tiotropium Bromide (Both Delivered by the Respimat® Inhaler) After 4 Weeks Once Daily Treatment in Patients Wi [NCT01040403]Phase 2233 participants (Actual)Interventional2010-01-31Completed
Single Dose Comparison of 3 Doses of Olodaterol in Double Fixed Dose Combination With BI54903 vs. 3 Doses of Olodaterol Mono in Free Combination [NCT01428622]Phase 20 participants (Actual)Interventional2011-10-31Withdrawn
Effectiveness and Safety of Maintenance Treatment With Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment With a Combination of Inhaled Corticosteroids and Long-acting β2 Agonists in COPD Patients [NCT04138758]42,953 participants (Actual)Observational2019-11-01Completed
INvestigating COPD Outcomes, Genomics and Neutrophilic Inflammation With Tiotropium and Olodaterol [NCT03152149]Phase 480 participants (Actual)Interventional2017-06-01Completed
A Randomised, Double-blind, Placebo- and Active-controlled Parallel Group Study to Assess the Efficacy of 12 Weeks of Once Daily Treatment of Two Doses of Orally Inhaled Tiotropium+ Olodaterol Fixed Dose Combination (Delivered by the Respimat Inhaler) in [NCT02006732]Phase 3809 participants (Actual)Interventional2013-11-30Completed
Effects of Tiotropium/Olodaterol on Cardio-pulmonary Exercise Capacity in Patients With Hyperinflated Chronic Obstructive Pulmonary Disease [ACHIEVE] [NCT04994574]44 participants (Anticipated)Interventional2021-08-31Not yet recruiting
A Randomised, Double-blind, 3-way Crossover Study to Compare Pharmacokinetics and Safety of 10 μg BI 1744 CL Plus 5 μg Tiotropium Bromide Given as Fixed Dose Combination Via the Respimat® Inhaler With the Pharmacokinetics and the Safety of the Single Agen [NCT02231177]Phase 147 participants (Actual)Interventional2008-06-30Completed
Acute and Two-week Effects of Spiolto® Respimat® (Tiotropium/Olodaterol) on Cardiac Function, the Autonomic Nervous System and Small Airway Function in Hyperinflated COPD Subjects [NCT04231214]Phase 432 participants (Actual)Interventional2020-01-28Completed
Phase II, Randomised, Double-Blind, Cross-over Study to Compare the 24-hour FEV1-time Profile of Orally Inhaled Olodaterol, Delivered With the Respimat® Inhaler, After 3 Weeks of Olodaterol Once Daily Medium Dose, Twice Daily Low Dose and Placebo or After [NCT01311661]Phase 2206 participants (Actual)Interventional2011-03-31Completed
Effectiveness and Safety of Maintenance Treatment With Combination of Tiotropium and Olodaterol in Comparison to Maintenance Treatment With a Combination of Inhaled Corticosteroids, Long-acting β2 Agonists and Long-acting Muscarinic Antagonists in COPD Pa [NCT04184297]27,190 participants (Actual)Observational2019-11-01Completed
Randomised, Double-blind, Double-dummy, Placebo-controlled, 4-way Cross-over Study to Characterise the 24-hour Forced, Expiratory Volume After 1 Second (FEV1) Time Profiles of BI 1744 CL 5µg and 10µg (Oral Inhalation, Delivered by the Respimat® Inhaler) a [NCT01040689]Phase 3108 participants (Actual)Interventional2010-01-31Completed
Cardiac Effects of Spiolto®/Respimat® in Patients With Congestive Heart Failure and COPD [NCT02812862]Phase 40 participants (Actual)Interventional2016-08-31Withdrawn(stopped due to Rationale obsolete)
A Randomised, Double-blinded, Active-controlled 2-way Cross Over Trial to Assess the Effects of 6 Weeks Treatment of Once Daily Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination Delivered by RESPIMAT Inhaler Compared With Tiotropium Delivered [NCT02629965]Phase 3184 participants (Actual)Interventional2016-02-12Completed
A Randomised, Double-blind, Parallel Group Study to Assess the Efficacy and Safety of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (2.5 µg / 5 µg; 5 µg / 5 µg) (Delivered by the Respimat® Inhaler) Compa [NCT01431274]Phase 32,624 participants (Actual)Interventional2011-09-30Completed
Effectiveness of Maintenance Treatment With Tiotropium + Olodaterol in Comparison to Inhaled Corticosteroids + Long-acting β2 Agonists in COPD Patients in Taiwan: a Non-interventional Study Based on the Taiwan National Health Insurance (NHI) Data [NCT05402020]20,775 participants (Actual)Observational2022-09-30Completed
AKTIV: Changes in Physical Functioning in Patients With COPD During Therapy With a Combination of Spiriva® Respimat® + Striverdi® Respimat® or Spiriva® 18 Mikrogramm + Striverdi® Respimat® [NCT02173769]1,845 participants (Actual)Observational2014-06-30Completed
A Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Determine the Effect of 12 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (2.5/5 µg and 5/5 µg) Delivered by the Respimat® Inhaler, on Exercise Endur [NCT01525615]Phase 3404 participants (Actual)Interventional2012-02-29Completed
An Exploratory, 12 Week, Randomised, Partially Double-blinded, Placebo-controlled Parallel Group Trial to Explore the Effects of Once Daily Treatments of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination or Tiotropium (Both Delivered by Respim [NCT02085161]Phase 3304 participants (Actual)Interventional2014-03-31Completed
A Randomised, Double Blind, Parallel Group Study to Assess the Efficacy and Safety of 12 Weeks of Once Daily, Orally Inhaled, Co-administration of Olodaterol 5µg (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) Compa [NCT01694771]Phase 31,134 participants (Actual)Interventional2012-09-30Completed
The Role of Inhaler Device in the Treatment Persistence With Dual Bronchodilators in Patients With COPD [NCT03979807]11,296 participants (Actual)Observational2019-06-10Completed
A Randomised, Double-blind, Placebo- and Active-controlled Parallel Group Study to Assess the Efficacy of 12 Weeks of Once Daily Treatment of Two Doses of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (Delivered by the Respimat Inhaler) in [NCT01964352]Phase 3813 participants (Actual)Interventional2013-11-30Completed
A Randomised, Placebo-controlled, Double-blind, Single Dose, Cross-over Study to Evaluate the Efficacy and Safety of Orally Inhaled Tiotropium + Olodaterol as Both a Fixed Dose Combination and a Free Combination (Both Delivered by the Respimat® Inhaler) i [NCT02030535]Phase 253 participants (Actual)Interventional2014-01-31Completed
A Randomised, Double-blind, Parallel-group Study to Assess the Safety and Efficacy of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed-dose Combination (2.5µg / 5µg, 5µg / 5µg ) and Olodaterol (5 µg) Delivered by the RESPIM [NCT01536262]Phase 3122 participants (Actual)Interventional2012-02-29Completed
Characteristics and Treatment Patterns of Patients With Chronic Obstructive Pulmonary Disease (COPD), Initiating Tio+Olo or Other Maintenance Therapies in the US and the UK: A Retrospective Claims Database Study [NCT04926233]1,371,146 participants (Actual)Observational2019-11-15Completed
A Randomized, Double-blind, Placebo-controlled, Multi-center, Parallel Group Study to Compare the Efficacy of Inhaled Tiotropium + Olodaterol, Fixed Dose Combination (5 mcg/5mcg) vs. Placebo Delivered by Respimat Inhaler in Patients With Moderate to Sever [NCT04223843]Phase 4213 participants (Actual)Interventional2020-01-08Completed
Drug Utilization Study for Olodaterol [NCT03030638]27,606 participants (Actual)Observational2017-02-08Completed
An Open-label Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After Single and Multiple Dose Treatment in Chinese Patients With Chronic Obstructive Pulmonary Dise [NCT02969317]Phase 112 participants (Actual)Interventional2017-02-24Completed
A Randomised, Double-blind, 5 Treatment Arms, 4-period, Incomplete Cross-over Study to Determine the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (FDC) (2.5 / 5 µg; and 5 / 5 µg) (Delivered by the Respimat® [NCT01533935]Phase 3291 participants (Actual)Interventional2012-02-29Completed
A 4-week, Randomised, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Tiotropium + Olodaterol Fixed Dose Combination (5/5 µg) Delivered by the Respimat® Inhaler Versus the Free Combination of Tiotropium 5 µg and Olodaterol 5 µg D [NCT02683109]Phase 4221 participants (Actual)Interventional2016-03-08Completed
A Randomised, Double-blind, Parallel Group Study to Assess the Efficacy and Safety of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (2.5 µg / 5 µg; 5 µg / 5 µg) (Delivered by the Respimat® Inhaler) Compa [NCT01431287]Phase 32,539 participants (Actual)Interventional2011-09-30Completed
Randomized, Double-blind, Double-dummy, Active-controlled, 4 Period Complete Cross-over Study to Compare the Effect on Lung Function of 6 Weeks Once Daily Treatment With Orally Inhaled Tiotropium+Olodaterol Fixed Dose Combination Delivered by the Respimat [NCT01969721]Phase 3229 participants (Actual)Interventional2013-10-31Completed
A Randomised, Open-label, Parallel-group Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After 3 Weeks Once Daily Treatment in Japanese Patients Wit [NCT01703845]Phase 132 participants (Actual)Interventional2012-10-31Completed
A Randomised, Double-blind, 5 Treatment Arms, 4-period, Incomplete Cross-over Study to Determine the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (FDC) (2.5 / 5 µg; and 5 / 5 µg) (Delivered by the Respimat® [NCT01533922]Phase 3295 participants (Actual)Interventional2012-03-31Completed
Randomised, Double-blind, Double-dummy, Placebo-controlled, 4-way Cross-over Study to Characterise the 24-hour FEV1-time Profiles of BI 1744 CL 5μg and 10μg (Oral Inhalation, Delivered by the Respimat® Inhaler) and Tiotropium Bromide 18μg (Oral Inhalation [NCT01040728]Phase 3122 participants (Actual)Interventional2010-01-31Completed
A Randomised, Double Blind, Parallel Group Study to Assess the Efficacy and Safety of 12 Weeks of Once Daily, Orally Inhaled, Co-administration of Olodaterol 5µg (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) Compa [NCT01696058]Phase 31,137 participants (Actual)Interventional2012-09-30Completed
Effects of Dual Bronchodilator Treatment (Tiotropium + Olodaterol Respimat) on Cardiopulmonary Interactions in Hyperinflated Patients With COPD [NCT03425617]Phase 425 participants (Actual)Interventional2017-01-01Completed
Randomised, Double-blind, Placebo-controlled, 6 Treatment, 4 Period, Incomplete Cross-over Trial to Characterise the 24-hour Lung Function Profiles of Tiotropium + Olodaterol Fixed Dose Combination (2.5/5 µg, 5/5 µg), Tiotropium (2.5 µg, 5 µg) and Olodate [NCT01559116]Phase 3219 participants (Actual)Interventional2012-03-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00452400 (33) [back to overview]Time From Dosing to the Maximum Concentration (Tmax)
NCT00452400 (33) [back to overview]Trough FEV1 Response After 2 Weeks
NCT00452400 (33) [back to overview]Trough FEV1 Response After 1 Week
NCT00452400 (33) [back to overview]Peak FVC (0-3h) Response After 4 Weeks
NCT00452400 (33) [back to overview]Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
NCT00452400 (33) [back to overview]Peak FEV1 (0-3h) Response After 4 Weeks
NCT00452400 (33) [back to overview]Peak FEV1 (0-3h) Response At Day 1
NCT00452400 (33) [back to overview]Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
NCT00452400 (33) [back to overview]Trough FVC Response After 2 Weeks
NCT00452400 (33) [back to overview]Area Under Curve From 0 to 3 Hours (AUC0-3)
NCT00452400 (33) [back to overview]Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
NCT00452400 (33) [back to overview]Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks
NCT00452400 (33) [back to overview]Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
NCT00452400 (33) [back to overview]Weekly Mean Evening PEFR After 4 Weeks
NCT00452400 (33) [back to overview]Trough FVC Response After 4 Weeks
NCT00452400 (33) [back to overview]Trough FVC Response After 1 Week
NCT00452400 (33) [back to overview]Trough FEV1 Response After 4 Weeks
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2
NCT00452400 (33) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
NCT00452400 (33) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
NCT00452400 (33) [back to overview]Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
NCT00452400 (33) [back to overview]Laboratory Testing: Average Change From Baseline of Potassium
NCT00452400 (33) [back to overview]Peak FEV1 (0-3h) Response After 1 Weeks
NCT00452400 (33) [back to overview]Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
NCT00452400 (33) [back to overview]Peak FEV1 (0-3h) Response After 2 Weeks
NCT00452400 (33) [back to overview]Maximum Concentration at Steady State (Cmax,ss)
NCT00452400 (33) [back to overview]Maximum Concentration (Cmax)
NCT00467740 (36) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1
NCT00467740 (36) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1
NCT00467740 (36) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4
NCT00467740 (36) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
NCT00467740 (36) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4
NCT00467740 (36) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4
NCT00467740 (36) [back to overview]Laboratory Testing: Average Change From Baseline of Potassium
NCT00467740 (36) [back to overview]Peak FEV1 (0-3h) Response After 1 Week
NCT00467740 (36) [back to overview]Peak FEV1 (0-3h) Response After 2 Weeks
NCT00467740 (36) [back to overview]Peak FVC (0-3h) Response After 1 Week
NCT00467740 (36) [back to overview]Peak FEV1 (0-3h) Response After 4 Weeks
NCT00467740 (36) [back to overview]Weekly Mean Evening PEFR After 4 Weeks
NCT00467740 (36) [back to overview]Trough FVC Response After 4 Weeks
NCT00467740 (36) [back to overview]Trough FVC Response After 2 Weeks
NCT00467740 (36) [back to overview]Trough FVC Response After 1 Week
NCT00467740 (36) [back to overview]Trough FEV1 Response After 4 Weeks
NCT00467740 (36) [back to overview]Trough FEV1 Response After 2 Weeks
NCT00467740 (36) [back to overview]Trough FEV1 Response After 1 Week
NCT00467740 (36) [back to overview]Total Score in Asthma Control Questionnaire After 4 Weeks
NCT00467740 (36) [back to overview]PEFR Variability After 4 Weeks
NCT00467740 (36) [back to overview]Peak FEV1 (0-3h) Response At Day 1
NCT00467740 (36) [back to overview]Peak FVC (0-3h) Response After 4 Weeks
NCT00467740 (36) [back to overview]Peak FVC (0-3h) Response After 2 Weeks
NCT00467740 (36) [back to overview]Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
NCT00467740 (36) [back to overview]Weekly Mean Pre-dose Morning PEFR After 4 Weeks
NCT00467740 (36) [back to overview]Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)
NCT00467740 (36) [back to overview]Area Under Curve From 0 to 3 Hours (AUC0-3)
NCT00467740 (36) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2
NCT00467740 (36) [back to overview]Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)
NCT00467740 (36) [back to overview]Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)
NCT00467740 (36) [back to overview]Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination
NCT00467740 (36) [back to overview]Peak FVC (0-3h) Response At Day 1
NCT00467740 (36) [back to overview]Maximum Concentration at Steady State (Cmax,ss)
NCT00467740 (36) [back to overview]Time From Dosing to the Maximum Concentration (Tmax)
NCT00467740 (36) [back to overview]Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)
NCT00467740 (36) [back to overview]Maximum Concentration (Cmax)
NCT00696020 (26) [back to overview]PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.
NCT00696020 (26) [back to overview]PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]Physician's Global Evaluation
NCT00696020 (26) [back to overview]Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.
NCT00696020 (26) [back to overview]Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]Weekly Mean Evening PEF [L/Min]
NCT00696020 (26) [back to overview]Weekly Mean Pre-dose Morning PEF [L/Min]
NCT00696020 (26) [back to overview]Tmax,ss Olodaterol [h]
NCT00696020 (26) [back to overview]Weekly Mean Number of Occasions of Rescue Therapy Used Per Day
NCT00696020 (26) [back to overview]Tmax,ss Tiotropium [h]
NCT00696020 (26) [back to overview]Trough FEV1 Response [L] After 4 Weeks of Treatment
NCT00696020 (26) [back to overview]FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.
NCT00696020 (26) [back to overview]FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
NCT00696020 (26) [back to overview]PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment
NCT00696020 (26) [back to overview]Patient's Global Rating
NCT00696020 (26) [back to overview]FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment
NCT00696020 (26) [back to overview]FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment
NCT00696020 (26) [back to overview]Cmax,ss Tiotropium [pg/mL]
NCT00696020 (26) [back to overview]Cmax,ss Olodaterol [pg/mL]
NCT00696020 (26) [back to overview]Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities
NCT00696020 (26) [back to overview]AUC(0-3h,ss) Tiotropium [pg*h/mL]
NCT00696020 (26) [back to overview]AUC(0-1h,ss) Olodaterol [pg*h/mL]
NCT00720499 (28) [back to overview]Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination
NCT00720499 (28) [back to overview]12-lead ECG QTcF Intervals
NCT00720499 (28) [back to overview]12-lead ECG QTcB Intervals
NCT00720499 (28) [back to overview]12-lead ECG QT Intervals
NCT00720499 (28) [back to overview]12-lead ECG QRS Intervals
NCT00720499 (28) [back to overview]12-lead ECG PR Intervals
NCT00720499 (28) [back to overview]12-lead ECG Heart Rate
NCT00720499 (28) [back to overview]PEFR Peak 0-3h Response
NCT00720499 (28) [back to overview]PEFR AUC (0-3h) Response
NCT00720499 (28) [back to overview]Overall Marked Changes From Baseline in Vital Signs
NCT00720499 (28) [back to overview]Individual FVC Measurements
NCT00720499 (28) [back to overview]Individual FEV1 Measurements
NCT00720499 (28) [back to overview]Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment.
NCT00720499 (28) [back to overview]Trough FEV1 Response [L] After 2 Weeks of Treatment
NCT00720499 (28) [back to overview]FVC AUC (0-3h) Response
NCT00720499 (28) [back to overview]FEV1 Peak 0-3h Response
NCT00720499 (28) [back to overview]FEV1 AUC 0-3h, Response
NCT00720499 (28) [back to overview]Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol])
NCT00720499 (28) [back to overview]Weekly Mean Morning PEFR
NCT00720499 (28) [back to overview]Weekly Mean Evening PEFR
NCT00720499 (28) [back to overview]Trough FVC Response
NCT00720499 (28) [back to overview]Physician's Global Evaluation
NCT00720499 (28) [back to overview]FEV1 (Unsupervised) AUC (6-12h) Response
NCT00720499 (28) [back to overview]FEV1, AUC (0-6h) Response
NCT00720499 (28) [back to overview]FVC AUC (0-6h) Response
NCT00720499 (28) [back to overview]FVC Peak 0-3h Response
NCT00720499 (28) [back to overview]Patient Global Rating
NCT00720499 (28) [back to overview]PEFR AUC (6-12h) Response
NCT00782210 (59) [back to overview]Peak FEV1 (0-3h) Response After 48 Weeks
NCT00782210 (59) [back to overview]Peak FEV1 (0-3h) Response After 6 Weeks
NCT00782210 (59) [back to overview]Peak FEV1 (0-3h) Response At Day 1
NCT00782210 (59) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00782210 (59) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization
NCT00782210 (59) [back to overview]Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00782210 (59) [back to overview]Trough FEV1 Response After 18 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response After 2 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response After 24 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response After 32 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response After 40 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response After 48 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response After 6 Weeks
NCT00782210 (59) [back to overview]Trough FEV1 Response at Day 85 (12 Weeks)
NCT00782210 (59) [back to overview]Trough FVC Response After 12 Weeks
NCT00782210 (59) [back to overview]Trough FVC Response After 18 Weeks
NCT00782210 (59) [back to overview]Trough FVC Response After 2 Weeks
NCT00782210 (59) [back to overview]Trough FVC Response After 24 Weeks
NCT00782210 (59) [back to overview]Trough FVC Response After 32 Weeks
NCT00782210 (59) [back to overview]Trough FVC Response After 48 Weeks
NCT00782210 (59) [back to overview]Trough FVC Response After 6 Weeks
NCT00782210 (59) [back to overview]Weekly Mean Daily (24h) Rescue Use
NCT00782210 (59) [back to overview]Weekly Mean Daytime Rescue Use
NCT00782210 (59) [back to overview]Weekly Mean Evening Peak Expiratory Flow Rate (PEF)
NCT00782210 (59) [back to overview]Weekly Mean Nighttime Rescue Use
NCT00782210 (59) [back to overview]Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)
NCT00782210 (59) [back to overview]Changes in Safety Parameters Related to Treatment
NCT00782210 (59) [back to overview]Trough FVC Response After 40 Weeks
NCT00782210 (59) [back to overview]Change From Baseline in Potassium
NCT00782210 (59) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
NCT00782210 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks
NCT00782210 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks
NCT00782210 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks
NCT00782210 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks
NCT00782210 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1
NCT00782210 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)
NCT00782210 (59) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
NCT00782210 (59) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks
NCT00782210 (59) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1
NCT00782210 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks
NCT00782210 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks
NCT00782210 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks
NCT00782210 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks
NCT00782210 (59) [back to overview]FVC Peak (0-3h) Response After 12 Weeks
NCT00782210 (59) [back to overview]FVC Peak (0-3h) Response After 2 Weeks
NCT00782210 (59) [back to overview]FVC Peak (0-3h) Response After 24 Weeks
NCT00782210 (59) [back to overview]FVC Peak (0-3h) Response After 48 Weeks
NCT00782210 (59) [back to overview]FVC Peak (0-3h) Response After 6 Weeks
NCT00782210 (59) [back to overview]FVC Peak (0-3h) Response At Day 1
NCT00782210 (59) [back to overview]Number of COPD Exacerbations
NCT00782210 (59) [back to overview]Number of COPD Exacerbations Requiring Hospitalization
NCT00782210 (59) [back to overview]Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
NCT00782210 (59) [back to overview]Patient's Global Rating at Week 12
NCT00782210 (59) [back to overview]Patient's Global Rating at Week 24
NCT00782210 (59) [back to overview]Patient's Global Rating at Week 48
NCT00782210 (59) [back to overview]Patient's Global Rating at Week 6
NCT00782210 (59) [back to overview]Peak FEV1 (0-3h) Response After 12 Weeks
NCT00782210 (59) [back to overview]Peak FEV1 (0-3h) Response After 2 Weeks
NCT00782210 (59) [back to overview]Peak FEV1 (0-3h) Response After 24 Weeks
NCT00782509 (59) [back to overview]FVC Peak (0-3h) Response After 2 Weeks
NCT00782509 (59) [back to overview]Peak FEV1 (0-3h) Response After 48 Weeks
NCT00782509 (59) [back to overview]Patient's Global Rating at Week 6
NCT00782509 (59) [back to overview]Trough FVC Response After 12 Weeks
NCT00782509 (59) [back to overview]Trough FEV1 Response at Day 85 (12 Weeks)
NCT00782509 (59) [back to overview]Trough FEV1 Response After 6 Weeks
NCT00782509 (59) [back to overview]Trough FVC Response After 6 Weeks
NCT00782509 (59) [back to overview]Weekly Mean Evening Peak Expiratory Flow Rate (PEF)
NCT00782509 (59) [back to overview]Weekly Mean of Daily (24h) Rescue Use
NCT00782509 (59) [back to overview]Weekly Mean of Daily Daytime Rescue Use
NCT00782509 (59) [back to overview]Weekly Mean of Daily Nighttime Rescue Use
NCT00782509 (59) [back to overview]Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)
NCT00782509 (59) [back to overview]Changes in Safety Parameters Related to Treatment
NCT00782509 (59) [back to overview]Change From Baseline in Potassium
NCT00782509 (59) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
NCT00782509 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks
NCT00782509 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks
NCT00782509 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks
NCT00782509 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks
NCT00782509 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1
NCT00782509 (59) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)
NCT00782509 (59) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)
NCT00782509 (59) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks
NCT00782509 (59) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1
NCT00782509 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks
NCT00782509 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks
NCT00782509 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks
NCT00782509 (59) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks
NCT00782509 (59) [back to overview]FVC Peak (0-3h) Response After 12 Weeks
NCT00782509 (59) [back to overview]Trough FEV1 Response After 48 Weeks
NCT00782509 (59) [back to overview]FVC Peak (0-3h) Response After 24 Weeks
NCT00782509 (59) [back to overview]FVC Peak (0-3h) Response After 48 Weeks
NCT00782509 (59) [back to overview]FVC Peak (0-3h) Response After 6 Weeks
NCT00782509 (59) [back to overview]FVC Peak (0-3h) Response At Day 1
NCT00782509 (59) [back to overview]Trough FEV1 Response After 40 Weeks
NCT00782509 (59) [back to overview]Trough FEV1 Response After 32 Weeks
NCT00782509 (59) [back to overview]Trough FEV1 Response After 24 Weeks
NCT00782509 (59) [back to overview]Trough FEV1 Response After 2 Weeks
NCT00782509 (59) [back to overview]Trough FEV1 Response After 18 Weeks
NCT00782509 (59) [back to overview]Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00782509 (59) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization
NCT00782509 (59) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00782509 (59) [back to overview]Peak FEV1 (0-3h) Response At Day 1
NCT00782509 (59) [back to overview]Peak FEV1 (0-3h) Response After 6 Weeks
NCT00782509 (59) [back to overview]Number of COPD Exacerbations
NCT00782509 (59) [back to overview]Number of COPD Exacerbations Requiring Hospitalization
NCT00782509 (59) [back to overview]Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
NCT00782509 (59) [back to overview]Patient's Global Rating at Week 12
NCT00782509 (59) [back to overview]Patient's Global Rating at Week 48
NCT00782509 (59) [back to overview]Peak FEV1 (0-3h) Response After 12 Weeks
NCT00782509 (59) [back to overview]Peak FEV1 (0-3h) Response After 2 Weeks
NCT00782509 (59) [back to overview]Trough FVC Response After 48 Weeks
NCT00782509 (59) [back to overview]Patient's Global Rating at Week 24
NCT00782509 (59) [back to overview]Trough FVC Response After 18 Weeks
NCT00782509 (59) [back to overview]Trough FVC Response After 2 Weeks
NCT00782509 (59) [back to overview]Trough FVC Response After 24 Weeks
NCT00782509 (59) [back to overview]Trough FVC Response After 32 Weeks
NCT00782509 (59) [back to overview]Trough FVC Response After 40 Weeks
NCT00782509 (59) [back to overview]Peak FEV1 (0-3h) Response After 24 Weeks
NCT00793624 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
NCT00793624 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
NCT00793624 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
NCT00793624 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
NCT00793624 (62) [back to overview]Absolute Plasma Concentrations
NCT00793624 (62) [back to overview]Changes in Safety Parameters Related to Treatment
NCT00793624 (62) [back to overview]Use of Rescue Medication at Week 24
NCT00793624 (62) [back to overview]Peak Expiratory Flow Rate (PEFR) at Week 24
NCT00793624 (62) [back to overview]Trough FVC Response at Week 6
NCT00793624 (62) [back to overview]Trough FVC Response at Week 48
NCT00793624 (62) [back to overview]Trough FVC Response at Week 40
NCT00793624 (62) [back to overview]Trough FVC Response at Week 32
NCT00793624 (62) [back to overview]Trough FVC Response at Week 24
NCT00793624 (62) [back to overview]Trough FVC Response at Week 2
NCT00793624 (62) [back to overview]Trough FVC Response at Week 18
NCT00793624 (62) [back to overview]Trough FVC Response at Week 12
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 6
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 48
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 40
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 32
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 24
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 2
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 18
NCT00793624 (62) [back to overview]Trough FEV1 Response at Week 12
NCT00793624 (62) [back to overview]Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation
NCT00793624 (62) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization
NCT00793624 (62) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00793624 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks
NCT00793624 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis
NCT00793624 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks
NCT00793624 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks
NCT00793624 (62) [back to overview]Peak FVC (0-3h) Response After 6 Weeks
NCT00793624 (62) [back to overview]Peak FEV1 (0-3h) Response After 24 Weeks
NCT00793624 (62) [back to overview]Peak FEV1 (0-3h) Response After 2 Weeks
NCT00793624 (62) [back to overview]Peak FEV1 (0-3h) Response After 12 Weeks
NCT00793624 (62) [back to overview]Patient's Global Rating (PGR) at 6 Weeks
NCT00793624 (62) [back to overview]Patient's Global Rating (PGR) at 48 Weeks
NCT00793624 (62) [back to overview]Patient's Global Rating (PGR) at 24 Weeks
NCT00793624 (62) [back to overview]Patient's Global Rating (PGR) at 12 Weeks
NCT00793624 (62) [back to overview]Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations
NCT00793624 (62) [back to overview]Number of COPD Exacerbations Requiring Hospitalization
NCT00793624 (62) [back to overview]Number of COPD Exacerbations
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 6 Weeks
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 48 Weeks
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 40 Weeks
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 32 Weeks
NCT00793624 (62) [back to overview]Peak FVC (0-3h) Response After 48 Weeks
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 18 Weeks
NCT00793624 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
NCT00793624 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 12 Weeks
NCT00793624 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
NCT00793624 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
NCT00793624 (62) [back to overview]Peak FVC (0-3h) Response After 24 Weeks
NCT00793624 (62) [back to overview]Peak FVC (0-3h) Response After 2 Weeks
NCT00793624 (62) [back to overview]Peak FVC (0-3h) Response After 12 Weeks
NCT00793624 (62) [back to overview]Peak FEV1 (0-3h) Response After 6 Weeks
NCT00793624 (62) [back to overview]Peak FEV1 (0-3h) Response After 48 Weeks
NCT00793624 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
NCT00793624 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
NCT00793624 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
NCT00796653 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
NCT00796653 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
NCT00796653 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
NCT00796653 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
NCT00796653 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
NCT00796653 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
NCT00796653 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
NCT00796653 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 12 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 18 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 32 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 40 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 48 Weeks
NCT00796653 (62) [back to overview]Mahler Transitional Dyspnea Index Focal Score at 6 Weeks
NCT00796653 (62) [back to overview]Number of COPD Exacerbations
NCT00796653 (62) [back to overview]Number of COPD Exacerbations Requiring Hospitalization
NCT00796653 (62) [back to overview]Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations
NCT00796653 (62) [back to overview]Patient's Global Rating (PGR) at 12 Weeks
NCT00796653 (62) [back to overview]Patient's Global Rating (PGR) at 24 Weeks
NCT00796653 (62) [back to overview]Patient's Global Rating (PGR) at 48 Weeks
NCT00796653 (62) [back to overview]Patient's Global Rating (PGR) at 6 Weeks
NCT00796653 (62) [back to overview]Peak FEV1 (0-3h) Response After 12 Weeks
NCT00796653 (62) [back to overview]Peak FEV1 (0-3h) Response After 2 Weeks
NCT00796653 (62) [back to overview]Peak FEV1 (0-3h) Response After 24 Weeks
NCT00796653 (62) [back to overview]Peak FEV1 (0-3h) Response After 48 Weeks
NCT00796653 (62) [back to overview]Peak FEV1 (0-3h) Response After 6 Weeks
NCT00796653 (62) [back to overview]Peak FVC (0-3h) Response After 12 Weeks
NCT00796653 (62) [back to overview]Peak FVC (0-3h) Response After 2 Weeks
NCT00796653 (62) [back to overview]Peak FVC (0-3h) Response After 24 Weeks
NCT00796653 (62) [back to overview]Peak FVC (0-3h) Response After 48 Weeks
NCT00796653 (62) [back to overview]Peak FVC (0-3h) Response After 6 Weeks
NCT00796653 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks
NCT00796653 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis
NCT00796653 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks
NCT00796653 (62) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT00796653 (62) [back to overview]Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization
NCT00796653 (62) [back to overview]Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 18
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 2
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 24
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 32
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 40
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 48
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 6
NCT00796653 (62) [back to overview]Trough FVC Response at Week 18
NCT00796653 (62) [back to overview]Trough FVC Response at Week 2
NCT00796653 (62) [back to overview]Trough FVC Response at Week 24
NCT00796653 (62) [back to overview]Trough FVC Response at Week 32
NCT00796653 (62) [back to overview]Trough FVC Response at Week 40
NCT00796653 (62) [back to overview]Trough FVC Response at Week 48
NCT00796653 (62) [back to overview]Trough FVC Response at Week 6
NCT00796653 (62) [back to overview]Changes in Safety Parameters Related to Treatment
NCT00796653 (62) [back to overview]Peak Expiratory Flow Rate (PEFR) at Week 24
NCT00796653 (62) [back to overview]Use of Rescue Medication at Week 24
NCT00796653 (62) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks
NCT00796653 (62) [back to overview]Trough FVC Response at Week 12
NCT00796653 (62) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
NCT00796653 (62) [back to overview]Absolute Plasma Concentrations
NCT00796653 (62) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
NCT00796653 (62) [back to overview]Trough FEV1 Response at Week 12
NCT00824382 (18) [back to overview]FEV1 Peak(0-3) Response at 4 Weeks
NCT00824382 (18) [back to overview]Trough FVC Response at Week 4
NCT00824382 (18) [back to overview]Weekly Mean Evening PEFR After 4 Weeks
NCT00824382 (18) [back to overview]AUC0-1,ss
NCT00824382 (18) [back to overview]Difference From Baseline in Potassium
NCT00824382 (18) [back to overview]FEV1 AUC(0-3) Response at 4 Weeks
NCT00824382 (18) [back to overview]FVC Peak(0-3) Response
NCT00824382 (18) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 0-6h (AUC 0-6h) Response After 4 Weeks
NCT00824382 (18) [back to overview]AUC0-1
NCT00824382 (18) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks
NCT00824382 (18) [back to overview]FVC AUC(0-3) Response
NCT00824382 (18) [back to overview]Cmax (Maximum Measured Concentration of the Analyte in Plasma)
NCT00824382 (18) [back to overview]Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
NCT00824382 (18) [back to overview]Trough FEV1 Response at Week 2
NCT00824382 (18) [back to overview]Trough FEV1 Response at Week 4
NCT00824382 (18) [back to overview]Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks
NCT00824382 (18) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination
NCT00824382 (18) [back to overview]Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State)
NCT00846768 (16) [back to overview]Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 24 Hours
NCT00846768 (16) [back to overview]Peak FVC (0-3h) Response After 3 Weeks
NCT00846768 (16) [back to overview]Peak FEV1 (0-3h) Response After 3 Weeks
NCT00846768 (16) [back to overview]FVC Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment
NCT00846768 (16) [back to overview]FVC Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment
NCT00846768 (16) [back to overview]Pharmacokinetics (PK): Concentration of the Analyte in Plasma Measured at 0.167 Hours Post Dosing at Steady State
NCT00846768 (16) [back to overview]FVC Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment
NCT00846768 (16) [back to overview]FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment
NCT00846768 (16) [back to overview]FEV1 Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment
NCT00846768 (16) [back to overview]FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment
NCT00846768 (16) [back to overview]Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 24 Hours
NCT00846768 (16) [back to overview]Trough FEV1 Response
NCT00846768 (16) [back to overview]Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 12 Hours
NCT00846768 (16) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination
NCT00846768 (16) [back to overview]Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 12 Hours
NCT00846768 (16) [back to overview]Trough FVC Response
NCT00928668 (7) [back to overview]Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 30 Minutes
NCT00928668 (7) [back to overview]Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 24 Hours
NCT00928668 (7) [back to overview]Laboratory Testing: Average Change From Baseline of Potassium and Calcium
NCT00928668 (7) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
NCT00928668 (7) [back to overview]Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 8 Hours
NCT00928668 (7) [back to overview]Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 4 Hours
NCT00928668 (7) [back to overview]Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 32 Hours
NCT00932646 (12) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
NCT00932646 (12) [back to overview]Trough FVC Response
NCT00932646 (12) [back to overview]Trough FEV1 Response
NCT00932646 (12) [back to overview]Peak FVC (0-3h) Response
NCT00932646 (12) [back to overview]FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT00932646 (12) [back to overview]FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT00932646 (12) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT00932646 (12) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment
NCT00932646 (12) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment
NCT00932646 (12) [back to overview]Peak FEV1 (0-3h) Response
NCT00932646 (12) [back to overview]FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment
NCT00932646 (12) [back to overview]FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment
NCT01013753 (31) [back to overview]Peak FVC Within 24 Hours Post-dose Response
NCT01013753 (31) [back to overview]Peak PEF Within 24 Hours Post-dose Response
NCT01013753 (31) [back to overview]PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT01013753 (31) [back to overview]PEF Daily Variability
NCT01013753 (31) [back to overview]Percentage of Asthma Symptom Free Days
NCT01013753 (31) [back to overview]Potassium 1 Hour Post-dose
NCT01013753 (31) [back to overview]Potassium 1 Hour Pre-dose
NCT01013753 (31) [back to overview]Potassium 3 Hours Post-dose
NCT01013753 (31) [back to overview]Total Asthma Control Questionnaire (ACQ) Score
NCT01013753 (31) [back to overview]Total Asthma Quality of Life Questionnaire (AQLQ(s)) Score
NCT01013753 (31) [back to overview]Trough FEV1 Response
NCT01013753 (31) [back to overview]Trough FVC Response
NCT01013753 (31) [back to overview]Trough PEF Response
NCT01013753 (31) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
NCT01013753 (31) [back to overview]Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
NCT01013753 (31) [back to overview]Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
NCT01013753 (31) [back to overview]Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
NCT01013753 (31) [back to overview]FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period
NCT01013753 (31) [back to overview]FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period
NCT01013753 (31) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period
NCT01013753 (31) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT01013753 (31) [back to overview]FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT01013753 (31) [back to overview]FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT01013753 (31) [back to overview]Mean Number of Puffs of Rescue Medication During the Whole Day
NCT01013753 (31) [back to overview]Mean Pre-dose Evening FEV1 (FEV1 p.m.)
NCT01013753 (31) [back to overview]Mean Pre-dose Evening PEF (PEF p.m.)
NCT01013753 (31) [back to overview]Mean Pre-dose Morning FEV1 (FEV1 a.m.)
NCT01013753 (31) [back to overview]Mean Pre-dose Morning PEF (PEF a.m.)
NCT01013753 (31) [back to overview]Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT01013753 (31) [back to overview]Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT01013753 (31) [back to overview]Peak FEV1 Within 24 Hours Post-dose Response
NCT01040130 (24) [back to overview]Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks
NCT01040130 (24) [back to overview]Number of Patients With Notable Increase in QRS Intervals
NCT01040130 (24) [back to overview]Number of Patients With Notable Increase in PR Intervals
NCT01040130 (24) [back to overview]Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks
NCT01040130 (24) [back to overview]Number of Patients With Notable Changes in Heart Rate
NCT01040130 (24) [back to overview]Change From Baseline to Day 43 in Blood Pressure
NCT01040130 (24) [back to overview]Change From Baseline to Day 43 in Pulse Rate
NCT01040130 (24) [back to overview]Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Endurance Time After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks
NCT01040130 (24) [back to overview]Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks
NCT01040403 (22) [back to overview]PEF Peak 0-3h Response After the First Dose
NCT01040403 (22) [back to overview]PEF AUC 0-3h Response After the First Dose
NCT01040403 (22) [back to overview]Patients Global Rating
NCT01040403 (22) [back to overview]FVC Peak 0-3h Response After the First Dose
NCT01040403 (22) [back to overview]FVC Peak 0-3h Response
NCT01040403 (22) [back to overview]FVC AUC 0-3h Response After First Dose
NCT01040403 (22) [back to overview]FEV1 Peak 0-3h Response After the First Dose
NCT01040403 (22) [back to overview]FEV1 Peak 0-3h Response
NCT01040403 (22) [back to overview]FEV1 AUC 0-3h Response After the First Dose
NCT01040403 (22) [back to overview]PEF Peak 0-3h Response
NCT01040403 (22) [back to overview]Weekly Mean Number of Puffs of Rescue Medication Used Per Day
NCT01040403 (22) [back to overview]Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry
NCT01040403 (22) [back to overview]Physicians Global Evaluation
NCT01040403 (22) [back to overview]PEF AUC 0-3h and AUC 0-6h Responses
NCT01040403 (22) [back to overview]Individual PEF Measurements at Each Time Point on Day 29
NCT01040403 (22) [back to overview]Individual FVC Measurements at Each Time Point on Day 29
NCT01040403 (22) [back to overview]Individual FEV1 Measurements at Each Time Point on Day 29
NCT01040403 (22) [back to overview]FVC AUC 0-3h and FEV1 AUC 0-6h Responses
NCT01040403 (22) [back to overview]FEV1 AUC 0-3h and FEV1 AUC 0-6h Response
NCT01040403 (22) [back to overview]Trough Forced Vital Capacity (FVC) Response
NCT01040403 (22) [back to overview]Trough FEV1 Response
NCT01040403 (22) [back to overview]Pulse Rate Recorded in Conjunction With Spirometry
NCT01040689 (16) [back to overview]Peak FVC (0-3h) Response
NCT01040689 (16) [back to overview]FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT01040689 (16) [back to overview]Peak FEV1 (0-3h) Response
NCT01040689 (16) [back to overview]FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment
NCT01040689 (16) [back to overview]FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment
NCT01040689 (16) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After First Dose of Treatment
NCT01040689 (16) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment
NCT01040689 (16) [back to overview]Peak FEV1 (0-3h) Response
NCT01040689 (16) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment
NCT01040689 (16) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT01040689 (16) [back to overview]FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT01040689 (16) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response
NCT01040689 (16) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response
NCT01040689 (16) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
NCT01040689 (16) [back to overview]Trough FVC Response
NCT01040689 (16) [back to overview]Trough FEV1 Response
NCT01040728 (16) [back to overview]Trough FEV1 Response
NCT01040728 (16) [back to overview]FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT01040728 (16) [back to overview]FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment
NCT01040728 (16) [back to overview]Peak FVC (0-3h) Response
NCT01040728 (16) [back to overview]Peak FEV1 (0-3h) Response
NCT01040728 (16) [back to overview]Peak FEV1 (0-3h) Response
NCT01040728 (16) [back to overview]FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT01040728 (16) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response
NCT01040728 (16) [back to overview]FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response
NCT01040728 (16) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT01040728 (16) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment
NCT01040728 (16) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After First Dose of Treatment
NCT01040728 (16) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment
NCT01040728 (16) [back to overview]FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment
NCT01040728 (16) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
NCT01040728 (16) [back to overview]Trough FVC Response
NCT01040793 (24) [back to overview]Adjusted Mean Endurance Time After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks
NCT01040793 (24) [back to overview]Change From Baseline to Day 43 in Pulse Rate
NCT01040793 (24) [back to overview]Change From Baseline to Day 43 in Blood Pressure
NCT01040793 (24) [back to overview]Number of Patients With Notable Changes in Heart Rate
NCT01040793 (24) [back to overview]Number of Patients With Notable Increase in PR Intervals
NCT01040793 (24) [back to overview]Number of Patients With Notable Increase in QRS Intervals
NCT01040793 (24) [back to overview]Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks
NCT01040793 (24) [back to overview]Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks
NCT01311661 (27) [back to overview]Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT01311661 (27) [back to overview]FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT01311661 (27) [back to overview]FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT01311661 (27) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period
NCT01311661 (27) [back to overview]Peak FVC Within 24 Hours Post-dose Response
NCT01311661 (27) [back to overview]Peak PEF Within 24 Hours Post-dose Response
NCT01311661 (27) [back to overview]Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)
NCT01311661 (27) [back to overview]PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response
NCT01311661 (27) [back to overview]PEF Daily Variability
NCT01311661 (27) [back to overview]Percentage of Asthma Symptom Free Days
NCT01311661 (27) [back to overview]FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period
NCT01311661 (27) [back to overview]FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period
NCT01311661 (27) [back to overview]Peak FEV1 Within 24 Hours Post-dose Response
NCT01311661 (27) [back to overview]Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response
NCT01311661 (27) [back to overview]Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response
NCT01311661 (27) [back to overview]Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)
NCT01311661 (27) [back to overview]Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)
NCT01311661 (27) [back to overview]Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG
NCT01311661 (27) [back to overview]Trough PEF Response
NCT01311661 (27) [back to overview]Trough FVC Response
NCT01311661 (27) [back to overview]Trough FEV1 Response
NCT01311661 (27) [back to overview]Total Asthma Control Questionnaire (ACQ) Score
NCT01311661 (27) [back to overview]Mean Pre-dose Morning PEF (PEF a.m.)
NCT01311661 (27) [back to overview]Mean Pre-dose Morning FEV1 (FEV1 a.m.)
NCT01311661 (27) [back to overview]Mean Pre-dose Evening PEF (PEF p.m.)
NCT01311661 (27) [back to overview]Mean Pre-dose Evening FEV1 (FEV1 p.m.)
NCT01311661 (27) [back to overview]Mean Number of Puffs of Rescue Medication During the Whole Day
NCT01431274 (30) [back to overview]FEV1 AUC(0-3h) Response on Day 1
NCT01431274 (30) [back to overview]FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]FEV1 AUC(0-12h) Response in the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Trough FEV1 Response on Day 15.
NCT01431274 (30) [back to overview]Trough FVC Response on Day 85.
NCT01431274 (30) [back to overview]Trough FVC Response on Day 43.
NCT01431274 (30) [back to overview]Trough FVC Response on Day 365.
NCT01431274 (30) [back to overview]Trough FVC Response on Day 170.
NCT01431274 (30) [back to overview]Trough FVC Response on Day 15.
NCT01431274 (30) [back to overview]Trough FEV1 Response on Day 85
NCT01431274 (30) [back to overview]Trough FEV1 Response on Day 43
NCT01431274 (30) [back to overview]Trough FEV1 Response on Day 365
NCT01431274 (30) [back to overview]Trough FEV1 Response on Day 170.
NCT01431274 (30) [back to overview]Trough FEV1 Response on Day 169
NCT01431274 (30) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]FVC AUC(0-24h) Response in Sub-set of Patients With 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]FVC AUC(0-12h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
NCT01431274 (30) [back to overview]FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85
NCT01431274 (30) [back to overview]FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365
NCT01431274 (30) [back to overview]FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169
NCT01431274 (30) [back to overview]FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1
NCT01431274 (30) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.
NCT01431274 (30) [back to overview]FEV1 AUC(0-3h) Response on Day 85
NCT01431274 (30) [back to overview]FEV1 AUC(0-3h) Response on Day 365
NCT01431287 (30) [back to overview]Trough FEV1 Response on Day 43
NCT01431287 (30) [back to overview]Trough FVC Response on Day 365
NCT01431287 (30) [back to overview]Trough FVC Response on Day 43
NCT01431287 (30) [back to overview]FVC AUC(0-12h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]FVC AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169
NCT01431287 (30) [back to overview]Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).
NCT01431287 (30) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]FEV1 AUC(0-12h) Response in Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 169
NCT01431287 (30) [back to overview]FEV1 AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]FEV1 AUC(0-3h) Response on Day 1
NCT01431287 (30) [back to overview]FEV1 AUC(0-3h) Response on Day 365
NCT01431287 (30) [back to overview]FEV1 AUC(0-3h) Response on Day 85
NCT01431287 (30) [back to overview]Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 1
NCT01431287 (30) [back to overview]Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 365
NCT01431287 (30) [back to overview]Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
NCT01431287 (30) [back to overview]Trough FEV1 Response on Day 15
NCT01431287 (30) [back to overview]Trough FEV1 Response on Day 169
NCT01431287 (30) [back to overview]Trough FEV1 Response on Day 170
NCT01431287 (30) [back to overview]Trough FEV1 Response on Day 365
NCT01431287 (30) [back to overview]Trough FEV1 Response on Day 85
NCT01431287 (30) [back to overview]Trough FVC Response on Day 15
NCT01431287 (30) [back to overview]Trough FVC Response on Day 85
NCT01431287 (30) [back to overview]Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 85
NCT01431287 (30) [back to overview]Trough FVC Response on Day 170
NCT01525615 (13) [back to overview]Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12
NCT01525615 (13) [back to overview]Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks
NCT01525615 (13) [back to overview]Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks
NCT01525615 (13) [back to overview]Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day
NCT01525615 (13) [back to overview]Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks
NCT01525615 (13) [back to overview]Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1
NCT01525615 (13) [back to overview]Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks
NCT01525615 (13) [back to overview]Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1
NCT01525615 (13) [back to overview]Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks
NCT01525615 (13) [back to overview]Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks
NCT01525615 (13) [back to overview]Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment
NCT01525615 (13) [back to overview]Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1
NCT01525615 (13) [back to overview]Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6
NCT01533922 (4) [back to overview]Slope of the Intensity of Breathing Discomfort During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity
NCT01533922 (4) [back to overview]Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
NCT01533922 (4) [back to overview]Forced Expiratory Volume in 1 Second (One Hour Post-dose)
NCT01533922 (4) [back to overview]Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
NCT01533935 (4) [back to overview]Slope of the Intensity of Breathing Discomfort (Borg Scale) During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
NCT01533935 (4) [back to overview]Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
NCT01533935 (4) [back to overview]FEV1 (1 Hour Post-dose)
NCT01533935 (4) [back to overview]Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity
NCT01536262 (3) [back to overview]Trough FEV1 Response
NCT01536262 (3) [back to overview]Number (%) of Patients With Drug-related AEs
NCT01536262 (3) [back to overview]FEV1 AUC0-3h Response
NCT01559116 (10) [back to overview]FVC AUC0-24h Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]Peak(0-3h) FEV1 Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]Peak (0-3h) FVC Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]Trough FEV1 Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]FVC AUC12-24h Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]FVC AUC0-12h Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]Forced Expiratory Volume in 1 Second (FEV1) AUC0-24h Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]Trough FVC Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]FEV1 AUC12-24h Response [L] After 6 Weeks Treatment.
NCT01559116 (10) [back to overview]FEV1 AUC0-12h Response [L] After 6 Weeks Treatment.
NCT01694771 (10) [back to overview]Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
NCT01694771 (10) [back to overview]Rescue Medication Usage - Percentage of Rescue Free Days
NCT01694771 (10) [back to overview]Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
NCT01694771 (10) [back to overview]Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
NCT01694771 (10) [back to overview]Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
NCT01694771 (10) [back to overview]Trough FVC Response at 12 Weeks- Defined as Change From Baseline
NCT01694771 (10) [back to overview]Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12
NCT01694771 (10) [back to overview]Peak FVC Response at 12 Weeks - Defined as Change From Baseline
NCT01694771 (10) [back to overview]FVC AUC0-3h Response at 12 Weeks - Defined as Change From Baseline
NCT01694771 (10) [back to overview]FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12
NCT01696058 (11) [back to overview]FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12
NCT01696058 (11) [back to overview]Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
NCT01696058 (11) [back to overview]Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
NCT01696058 (11) [back to overview]Peak FVC Response at 12 Weeks; Defined as Change From Baseline
NCT01696058 (11) [back to overview]Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data
NCT01696058 (11) [back to overview]Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12
NCT01696058 (11) [back to overview]Trough FVC Response at 12 Weeks; Defined as Change From Baseline
NCT01696058 (11) [back to overview]Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
NCT01696058 (11) [back to overview]Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
NCT01696058 (11) [back to overview]Rescue Medication Usage - Percentage of Rescue Free Days
NCT01696058 (11) [back to overview]FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline
NCT01703845 (16) [back to overview]CLR,t1-t2,ss (Tiotropium)
NCT01703845 (16) [back to overview]Aet1-t2,ss (Olodaterol)
NCT01703845 (16) [back to overview]AUC0-tz,ss (Olodaterol)
NCT01703845 (16) [back to overview]AUC0-tz,ss (Tiotropium)
NCT01703845 (16) [back to overview]AUCt1-t2,ss (Olodaterol)
NCT01703845 (16) [back to overview]AUCt1-t2,ss (Tiotropium)
NCT01703845 (16) [back to overview]CLR,t1-t2,ss (Olodaterol)
NCT01703845 (16) [back to overview]Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG
NCT01703845 (16) [back to overview]Cmax,ss (Olodaterol)
NCT01703845 (16) [back to overview]fe t1-t2,ss (Olodaterol)
NCT01703845 (16) [back to overview]fe t1-t2,ss (Tiotropium)
NCT01703845 (16) [back to overview]Cmax,ss (Tiotropium)
NCT01703845 (16) [back to overview]Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)
NCT01703845 (16) [back to overview]Tmax,ss (Olodaterol)
NCT01703845 (16) [back to overview]Tmax,ss (Tiotropium)
NCT01703845 (16) [back to overview]Aet1-t2,ss (Tiotropium)
NCT01964352 (6) [back to overview]FVC AUC0-3h Response (Change From Baseline)
NCT01964352 (6) [back to overview]FEV1 AUC0-3h Response
NCT01964352 (6) [back to overview]TDI Focal Score
NCT01964352 (6) [back to overview]Trough FEV1 Response (Change From Baseline)
NCT01964352 (6) [back to overview]Trough Forced Vital Capacity (FVC) Response (Change From Baseline)
NCT01964352 (6) [back to overview]St. George's Respiratory Questionnaire (SGRQ) Total Score
NCT01969721 (5) [back to overview]Trough FEV1 Change From Patient Baseline After 6 Weeks of Treatment
NCT01969721 (5) [back to overview]FEV1 AUC (0-12h) Change From Patient Baseline After 6 Weeks of Treatment
NCT01969721 (5) [back to overview]FEV1 AUC (0-24h) Change From Patient Baseline After 6 Weeks of Treatment
NCT01969721 (5) [back to overview]FEV1 AUC (12-24h) Change From Patient Baseline After 6 Weeks of Treatment
NCT01969721 (5) [back to overview]FEV1 Peak (0-3h) Change From Patient Baseline After 6 Weeks of Treatment
NCT02006732 (8) [back to overview]St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Combined Dataset From This Study and the Replicate Study NCT01964352
NCT02006732 (8) [back to overview]TDI Focal Score Based on Combined Dataset From This Study and the Replicate Study NCT01964352
NCT02006732 (8) [back to overview]St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Data From This Individual Study
NCT02006732 (8) [back to overview]FVC AUC0-3h Response (Change From Baseline)
NCT02006732 (8) [back to overview]FEV1 AUC0-3h Response
NCT02006732 (8) [back to overview]TDI Focal Score Based on Data From This Individual Study
NCT02006732 (8) [back to overview]Trough FEV1 Response (Change From Baseline)
NCT02006732 (8) [back to overview]Trough Forced Vital Capacity (FVC) Response (Change From Baseline)
NCT02030535 (21) [back to overview]QRS Change From Patient Baseline at Individual Post-dose Time Points
NCT02030535 (21) [back to overview]QT Change From Patient Baseline at Individual Post-dose Time Points
NCT02030535 (21) [back to overview]QTcB Change From Patient Baseline at Individual Post-dose Time Points
NCT02030535 (21) [back to overview]RR Change From Patient Baseline at Individual Post-dose Time Points
NCT02030535 (21) [back to overview]Peak PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Peak Heart Rate Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean RR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean Heart Rate Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Peak QTcF Interval Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Peak RR Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean (Heart Rate Corrected QT Interval (Using Fredericia Adjustment)) QTcF Interval Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3hours) Response After Single-dose Administration
NCT02030535 (21) [back to overview]Peak QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points
NCT02030535 (21) [back to overview]Heart Rate Change From Patient Baseline at Individual Post-dose Time Points
NCT02030535 (21) [back to overview]PR Change From Patient Baseline at Individual Post-dose Time Points
NCT02030535 (21) [back to overview]Peak QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points
NCT02085161 (8) [back to overview]Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks
NCT02085161 (8) [back to overview]One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment
NCT02085161 (8) [back to overview]One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment
NCT02085161 (8) [back to overview]Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 12
NCT02085161 (8) [back to overview]Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12
NCT02085161 (8) [back to overview]Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment
NCT02085161 (8) [back to overview]Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment
NCT02085161 (8) [back to overview]Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks
NCT02173769 (7) [back to overview]General Health of the Patient After 4-6 Weeks
NCT02173769 (7) [back to overview]General Health of the Patient at Baseline
NCT02173769 (7) [back to overview]Patient Satisfaction: Overall Satisfaction
NCT02173769 (7) [back to overview]Patient Satisfaction: Satisfaction With Handling of Inhaler
NCT02173769 (7) [back to overview]Patient Satisfaction: Satisfaction With Inhaler
NCT02173769 (7) [back to overview]"Percentage of Participants With Therapeutic Success"
NCT02173769 (7) [back to overview]Absolute Changes in the PF-10 Score
NCT02231177 (23) [back to overview]Ae(0-24h,ss) of Olodaterol
NCT02231177 (23) [back to overview]AUC(0-1h,ss) of Olodaterol
NCT02231177 (23) [back to overview]AUC(0-2h,ss) of Olodaterol
NCT02231177 (23) [back to overview]AUC(0-4h,ss) of Tiotropium
NCT02231177 (23) [back to overview]AUC(0-tz,ss) of Olodaterol
NCT02231177 (23) [back to overview]Tmax,ss of Tiotropium
NCT02231177 (23) [back to overview]Cmax,ss of Olodaterol
NCT02231177 (23) [back to overview]AUC(0-6h,ss) of Tiotropium
NCT02231177 (23) [back to overview]Cmax,ss of Tiotropium
NCT02231177 (23) [back to overview]Cmin,ss of Olodaterol
NCT02231177 (23) [back to overview]Cmin,ss of Tiotropium
NCT02231177 (23) [back to overview]fe(0-24,ss) of Olodaterol
NCT02231177 (23) [back to overview]Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG
NCT02231177 (23) [back to overview]fe(0-24,ss) of Tiotropium
NCT02231177 (23) [back to overview]Tmax,ss of Olodaterol
NCT02231177 (23) [back to overview]AUC(0-tz,ss) of Tiotropium
NCT02231177 (23) [back to overview]FVC Change From Baseline
NCT02231177 (23) [back to overview]FEV1 Change From Baseline
NCT02231177 (23) [back to overview]Ae(0-24h,ss) of Tiotropium
NCT02231177 (23) [back to overview]Tmin,ss of Tiotropium
NCT02231177 (23) [back to overview]Tmin,ss of Olodaterol
NCT02231177 (23) [back to overview]Concentration of Olodaterol in Plasma
NCT02231177 (23) [back to overview]Concentration of Tiotropium in Plasma
NCT02296138 (5) [back to overview]Annualised Rate of Exacerbations Leading to Hospitalisation During the Actual Treatment Period.
NCT02296138 (5) [back to overview]Annualised Rate of Moderate to Severe COPD Exacerbations During the Actual Treatment Period.
NCT02296138 (5) [back to overview]Number of Patients With All-cause Mortality Occurring During the Actual Treatment Period.
NCT02296138 (5) [back to overview]Number of Patients With at Least One COPD Exacerbation Leading to Hospitalisation During the Actual Treatment Period.
NCT02296138 (5) [back to overview]Number of Patients With at Least One Moderate to Severe COPD Exacerbation During the Actual Treatment Period.
NCT02629965 (16) [back to overview]Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs)
NCT02629965 (16) [back to overview]Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs)
NCT02629965 (16) [back to overview]Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs
NCT02629965 (16) [back to overview]60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre)
NCT02629965 (16) [back to overview]6-minute Walk Distance [Meter]
NCT02629965 (16) [back to overview]30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre)
NCT02629965 (16) [back to overview]Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose
NCT02629965 (16) [back to overview]30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre)
NCT02629965 (16) [back to overview]Average Number of Step Per Day (Step/Day)
NCT02629965 (16) [back to overview]Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs)
NCT02629965 (16) [back to overview]Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage III/IV
NCT02629965 (16) [back to overview]Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I/II
NCT02629965 (16) [back to overview]Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) in-Completer at Baseline Period
NCT02629965 (16) [back to overview]Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Treatment Period
NCT02629965 (16) [back to overview]Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Baseline Period
NCT02629965 (16) [back to overview]Inspiratory Capacity [Litre] Test Comparisons of 6-Minute Walk Treatment (6MWT) in-Completer at Treatment Period
NCT02683109 (3) [back to overview]Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment
NCT02683109 (3) [back to overview]Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment
NCT02683109 (3) [back to overview]Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Borg CR-10 Rating of Perceived Dyspnea During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Borg CR-10 Rating of Perceived Leg Fatigue During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Frontal Lobe Oxygen Saturation During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime in Pulse Oximeter Oxygen Saturation During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Inspiratory Capacity During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Muscle Oxygen Saturation During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Oxygen Uptake (VO2) During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Ventilation During CWR
NCT02845752 (14) [back to overview]Change From Period Baseline in the Forced Expiratory Volume in 1 Second (FEV1)
NCT02845752 (14) [back to overview]Change From Period Baseline in the Pre/Post Exercise-induced Decline in Peak Isokinetic Power Normalized to the Measured Muscle Activity (Muscle Fatigue, MF) During CWR
NCT02845752 (14) [back to overview]Exercise Endurance Time During CWR Cycling Exercise
NCT02845752 (14) [back to overview]The Magnitude of Change Electromyographic (EMG) Muscle Activity (Activation Fatigue, AF) Associated With Stiolto Respimat Compared With Placebo Respimat at Isotime During Constant Work Rate Exercise (CWR)
NCT02845752 (14) [back to overview]The Magnitude of Change in Isokinetic Power (Performance Fatigue, PF) Associated With Stiolto Respimat Compared With Placebo Respimat at Isotime During Constant Work Rate Exercise (CWR)
NCT02845752 (14) [back to overview]Change From Period Baseline in the Exercise-isotime Inspiratory Reserve Volume During CWR
NCT02853123 (8) [back to overview]Change From Baseline in Intensity of Breathlessness Measured Using the Modified Borg Scale at the End of the 3 Minute (Min) Constant Speed Shuttle Test After 6 Weeks of Treatment.
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for Intensity of Breathlessness (MBS-S) at 1, 2 and 2.5 Minute (Min) During the 3 Min Constant Speed Shuttle Test
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured Prior to Exercise
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) Dyspnoea Domain Score
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Expiratory Volume
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Vital Capacity
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured at the End of Exercise
NCT02853123 (8) [back to overview]Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Individualized (CRQ-SAI) Dyspnoea Domain Score
NCT02864407 (17) [back to overview]Percentage of Subjects With Any Adverse Event (AE) in the Long-term Safety Analysis Set
NCT02864407 (17) [back to overview]Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Long-term Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Long-term Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Percentage of Subjects With Any Adverse Drug Reaction, Serious Adverse Drug Reaction, Unexpected Adverse Drug Reaction, Unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction Leading to Discontinuation
NCT02864407 (17) [back to overview]Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation
NCT02864407 (17) [back to overview]Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Effectiveness Rate in the Effectiveness Analysis Set
NCT02864407 (17) [back to overview]Effectiveness Rate in the Long-term Effectiveness Analysis Set
NCT02969317 (16) [back to overview]Maximum Measured Concentration of Olodaterol in Plasma (Cmax)
NCT02969317 (16) [back to overview]Maximum Measured Concentration of Tiotropium in Plasma (Cmax)
NCT02969317 (16) [back to overview]Maximum Measured Concentration of Tiotropium in Plasma at Steady State (Cmax,ss)
NCT02969317 (16) [back to overview]Pre-dose Concentration of Olodaterol in Plasma at Steady State (Cpre,ss)
NCT02969317 (16) [back to overview]Pre-dose Concentration of Tiotropium in Plasma at Steady State (Cpre,ss)
NCT02969317 (16) [back to overview]Time From Dosing to the Maximum Concentration of Olodaterol in Plasma (Tmax)
NCT02969317 (16) [back to overview]Time From Dosing to the Maximum Concentration of Olodaterol in Plasma at Steady State (Tmax,ss)
NCT02969317 (16) [back to overview]Time From Dosing to the Maximum Concentration of Tiotropium in Plasma at Steady State (Tmax,ss)
NCT02969317 (16) [back to overview]Accumulation Ratios in Plasma of Olodaterol (RA,Cmax =Cmax,ss/Cmax)
NCT02969317 (16) [back to overview]Accumulation Ratios in Plasma of Tiotropium (RA,Cmax =Cmax,ss/Cmax)
NCT02969317 (16) [back to overview]Area Under the Concentration Time Curve of Olodaterol in Plasma Over the Time Interval From 0 to 6 Hours at Steady State (AUC0-6,ss)
NCT02969317 (16) [back to overview]Area Under the Concentration Time Curve of Tiotropium in Plasma Over the Time Interval From 0 to 6 Hours at Steady State (AUC0-6,ss)
NCT02969317 (16) [back to overview]Area Under the Concentration-time Curve of Olodaterol in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)
NCT02969317 (16) [back to overview]Area Under the Concentration-time Curve of Tiotropium in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)
NCT02969317 (16) [back to overview]Time From Dosing to the Maximum Concentration of Tiotropium in Plasma (Tmax)
NCT02969317 (16) [back to overview]Maximum Measured Concentration of Olodaterol in Plasma at Steady State (Cmax,ss)
NCT03030638 (4) [back to overview]Baseline Characteristics of New Users of Indacaterol: Age
NCT03030638 (4) [back to overview]Baseline Characteristics of New Users of Olodaterol: Age
NCT03030638 (4) [back to overview]Percentage of Off-label Use of Indacaterol Among New Users
NCT03030638 (4) [back to overview]Percentage of Off-label Use of Olodaterol Among New Users
NCT03055988 (9) [back to overview]Change From Baseline in 1.5 Hour Post Dose Forced Expiratory Volume in 1st Second (FEV1) After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Aortic Augmentation Index After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Pulse Pressure After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Pulmonary Artery Pulsatility After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) in the 6th Week of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % Predicted After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Central Systolic Pressure After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in 1.5 Hour Post Dose Forced Vital Capacity (FVC) After 6 Weeks of Treatment
NCT03055988 (9) [back to overview]Change From Baseline in Aortic Distensibility After 6 Weeks of Treatment
NCT03240575 (4) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment
NCT03240575 (4) [back to overview]Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment
NCT03240575 (4) [back to overview]Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment
NCT03240575 (4) [back to overview]Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment
NCT03673670 (14) [back to overview]Residual Volume on Day 3
NCT03673670 (14) [back to overview]Functional Residual Capacity on Day 3
NCT03673670 (14) [back to overview]Change From Baseline in Peak FEV1 After Evening Dose on Day 3
NCT03673670 (14) [back to overview]Change From Baseline in Peak FEV1 on Day 3
NCT03673670 (14) [back to overview]Change From Baseline in Peak FEV1 on Day 1
NCT03673670 (14) [back to overview]Specific Airway Conductance on Day 1
NCT03673670 (14) [back to overview]Specific Airway Conductance on Day 3
NCT03673670 (14) [back to overview]Residual Volume on Day 1
NCT03673670 (14) [back to overview]Functional Residual Capacity on Day 1
NCT03673670 (14) [back to overview]Determination of Onset of Action on Day 1
NCT03673670 (14) [back to overview]Change From Baseline to Trough FEV1 on Day 4
NCT03673670 (14) [back to overview]Change From Baseline in AUC0-12h FEV1 on Day 1
NCT03673670 (14) [back to overview]Change From Baseline in AUC0-12h FEV1 on Day 3
NCT03673670 (14) [back to overview]Change From Baseline in AUC0-4h FEV1 on Day 3
NCT03979807 (1) [back to overview]Rate of Discontinuation of Index Treatment (Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol)
NCT04011475 (12) [back to overview]Annualized Rate of Moderate-to-severe Exacerbation
NCT04011475 (12) [back to overview]Annualized Rate of Moderate Exacerbation
NCT04011475 (12) [back to overview]Percentage of Patients Using Rescue Medications
NCT04011475 (12) [back to overview]Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by COPD Assessment Test (CAT) Score at 12 Months After Index Date
NCT04011475 (12) [back to overview]Annualized Rate of Mild Exacerbation
NCT04011475 (12) [back to overview]Annualized Rate of Severe Exacerbation
NCT04011475 (12) [back to overview]Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by Modified Medical Research Council Dyspnea Scale (mMRC) at 12 Months After Index Date
NCT04011475 (12) [back to overview]Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by Post-bronchodilator Forced Expiratory Volume in One Second (Post-FEV1) at 12 Months After Index Date
NCT04011475 (12) [back to overview]Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by Post-bronchodilator Forced Volume Vital Capacity (Post-FVC) at 12 Months After Index Date
NCT04011475 (12) [back to overview]Incidence of Patients Escalating Therapy (From Single/Dual to Dual/Triple Therapy)
NCT04011475 (12) [back to overview]Number of Participants With Moderate-to-severe Acute Exacerbation
NCT04011475 (12) [back to overview]Percentage of Patients Receiving Dual Therapy Escalated to Triple Therapy or LAMA Escalated to Dual Therapy
NCT04138758 (6) [back to overview]Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy
NCT04138758 (6) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT04138758 (6) [back to overview]Incidence Rate of First Hospitalization for Community-acquired Pneumonia
NCT04138758 (6) [back to overview]Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy
NCT04138758 (6) [back to overview]Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy
NCT04138758 (6) [back to overview]Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy
NCT04184297 (3) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT04184297 (3) [back to overview]Overall Incidence Rate of Hospitalization for Community-acquired Pneumonia (Serious Pneumonia)
NCT04184297 (3) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation - Without Exacerbation Within 30 Days Prior to Cohort Entry
NCT04223843 (2) [back to overview]Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment
NCT04223843 (2) [back to overview]Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.
NCT04249310 (3) [back to overview]Time to Triple Therapy Initiation
NCT04249310 (3) [back to overview]Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
NCT04249310 (3) [back to overview]Number of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
NCT04672941 (16) [back to overview]Percentage of Patients With Improved / Worsen Condition in Self-care According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months
NCT04672941 (16) [back to overview]Percentage of Patients With Adherence to the Medication
NCT04672941 (16) [back to overview]Percentage of Patients by Preference for Inhaler
NCT04672941 (16) [back to overview]Change From Baseline in Patients' Quality of Life (QoL) According to the Total Score of COPD Assessment Test (CAT) at Month 3
NCT04672941 (16) [back to overview]Percentage of Patients With Improved / Worsen Condition Pain/Discomfort According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months
NCT04672941 (16) [back to overview]Total Score in Abbreviated Patient Satisfaction and Preference Questionnaire (PASAPQ)
NCT04672941 (16) [back to overview]Percentage of Patients With Improved / Worsened Condition Mobility According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months
NCT04672941 (16) [back to overview]Number of Patients Adherence to Medication of COPD Patients According to the Simplified Medication Adherence Questionnaire (SMAQ) Three-months After the Switch
NCT04672941 (16) [back to overview]Overall Satisfaction of Inhaler
NCT04672941 (16) [back to overview]Days of Missed Medication for COPD
NCT04672941 (16) [back to overview]Willingness to Continue With Inhaler
NCT04672941 (16) [back to overview]Change From Baseline in the Percentage of Patients With CAT≥10 at Month 3
NCT04672941 (16) [back to overview]Change From Baseline in the Total European Quality of Life-Visual Analogue Scale (EQ-VAS) at Month 3
NCT04672941 (16) [back to overview]Percentage of Patients With Improved / Worsen Condition Anxiety/Depression According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months
NCT04672941 (16) [back to overview]Change From Baseline of Patients' Dyspnea Status According to the Modified Medical Research Council (mMRC) Scale at Month 3
NCT04672941 (16) [back to overview]Percentage of Patients With Improved / Worsen Condition Usual Activities According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months
NCT04926233 (21) [back to overview]Characteristics of Patients Receiving Second Maintenance Treatment - UK
NCT04926233 (21) [back to overview]Characteristics of Patients Receiving Second Maintenance Treatment - US
NCT04926233 (21) [back to overview]Number of Participants With Zero Exacerbations in the Year Prior to the Start of Second Maintenance Therapy - UK
NCT04926233 (21) [back to overview]Age of the Chronic Obstructive Pulmonary Disease (COPD) Patients at the Time of COPD Diagnosis - US
NCT04926233 (21) [back to overview]Age of Patients Receiving First Maintenance Treatment - UK
NCT04926233 (21) [back to overview]Age of Patients Receiving First Maintenance Treatment - US
NCT04926233 (21) [back to overview]Age of Patients Receiving Second Maintenance Treatment - UK
NCT04926233 (21) [back to overview]Age of Patients Receiving Second Maintenance Treatment - US
NCT04926233 (21) [back to overview]Age of the Chronic Obstructive Pulmonary Disease (COPD) Patients at the Time of COPD Diagnosis - UK
NCT04926233 (21) [back to overview]Charlson Comorbidity Index (CCI) at the Time of COPD Diagnosis
NCT04926233 (21) [back to overview]Charlson Comorbidity Index (CCI) of Patients Receiving First Maintenance Treatment - US
NCT04926233 (21) [back to overview]Charlson Comorbidity Index (CCI) of Patients Receiving Second Maintenance Treatment - US
NCT04926233 (21) [back to overview]Days Between First and Second Maintenance Therapy - UK
NCT04926233 (21) [back to overview]Days Between First and Second Maintenance Therapy - US
NCT04926233 (21) [back to overview]Days Between Index and Initiation of First Maintenance Therapy - UK
NCT04926233 (21) [back to overview]Days Between Index and Initiation of First Maintenance Therapy - US
NCT04926233 (21) [back to overview]Number of Participants With Zero Exacerbations in the Year Prior to the Start of First Maintenance Therapy - UK
NCT04926233 (21) [back to overview]Number of Participants With Zero Exacerbations in the Year Prior to the Start of First Maintenance Therapy - US
NCT04926233 (21) [back to overview]Number of Participants With Zero Exacerbations in the Year Prior to the Start of Second Maintenance Therapy - US
NCT04926233 (21) [back to overview]Characteristics of Patients Receiving First Maintenance Treatment - US
NCT04926233 (21) [back to overview]Characteristics of Patients Receiving First Maintenance Treatment - UK
NCT05127304 (21) [back to overview]COPD or Pneumonia-attributable Health Care Costs (Insurer + Patient Paid Amounts)
NCT05127304 (21) [back to overview]COPD and/or Pneumonia-related Health Care Resource Utilization
NCT05127304 (21) [back to overview]COPD and/or Pneumonia-related Health Care Costs (Insurer + Patient Paid Amounts)
NCT05127304 (21) [back to overview]Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
NCT05127304 (21) [back to overview]All-cause Health Care Resource Utilization
NCT05127304 (21) [back to overview]All-cause Health Care Costs (Insurer + Patient Paid Amounts)
NCT05127304 (21) [back to overview]Pneumonia-related Health Care Resource Utilization: Inpatient Days
NCT05127304 (21) [back to overview]Percentage of Patients With 30-day All-cause Readmission After COPD Hospitalization
NCT05127304 (21) [back to overview]COPD-related Health Care Resource Utilization: Pharmacy Fills
NCT05127304 (21) [back to overview]COPD-related Health Care Resource Utilization: Inpatient Days
NCT05127304 (21) [back to overview]COPD or Pneumonia-attributable Health Care Resource Utilization: Pharmacy Fills
NCT05127304 (21) [back to overview]COPD or Pneumonia-attributable Health Care Resource Utilization: Inpatient Days
NCT05127304 (21) [back to overview]COPD-related Health Care Resource Utilization
NCT05127304 (21) [back to overview]COPD and/or Pneumonia-related Health Care Resource Utilization: Pharmacy Fills
NCT05127304 (21) [back to overview]COPD and/or Pneumonia-related Health Care Resource Utilization: Inpatient Days
NCT05127304 (21) [back to overview]All-cause Health Care Resource Utilization: Inpatient Days
NCT05127304 (21) [back to overview]All-cause Health Care Resource Utilization: Pharmacy Fills
NCT05127304 (21) [back to overview]COPD or Pneumonia-attributable Health Care Resource Utilization
NCT05127304 (21) [back to overview]Pneumonia-related Health Care Resource Utilization
NCT05127304 (21) [back to overview]COPD-related Health Care Costs (Insurer + Patient Paid Amounts)
NCT05127304 (21) [back to overview]Pneumonia-related Health Care Costs (Insurer + Patient Paid Amounts)
NCT05169424 (13) [back to overview]Total Costs of All-cause HCRU
NCT05169424 (13) [back to overview]Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position) - Among Patients With no Baseline Exacerbation
NCT05169424 (13) [back to overview]Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position) - Among Patients With 2 or More Baseline Exacerbations
NCT05169424 (13) [back to overview]Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position) - Among Patients With 0 or 1 Baseline Exacerbation
NCT05169424 (13) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry
NCT05169424 (13) [back to overview]Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position)
NCT05169424 (13) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry - Among Patients With no Baseline Exacerbation
NCT05169424 (13) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry - Among Patients With 2 or More Baseline Exacerbations
NCT05169424 (13) [back to overview]Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry - Among Patients With 0 or 1 Baseline Exacerbation
NCT05169424 (13) [back to overview]Total Costs of COPD-related HCRU
NCT05169424 (13) [back to overview]Total Costs of COPD or Pneumonia-related Health Care Cost and Resource Utilization (HCRU)
NCT05169424 (13) [back to overview]Total Costs of COPD or Pneumonia Attributable HCRU
NCT05169424 (13) [back to overview]Total Costs of Pneumonia-related HCRU

Time From Dosing to the Maximum Concentration (Tmax)

tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma. (NCT00452400)
Timeframe: Baseline and 4 weeks

,,
Interventionhours (Median)
Olodaterol (N=0;0;40;71;69)Olodaterol glucuronide (N=0;0;54;71;66)
Olo 10 mcg qd0.1833.00
Olo 20 mcg qd0.2003.00
Olo 5 mcg qd0.1672.95

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Trough FEV1 Response After 2 Weeks

Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication. (NCT00452400)
Timeframe: Baseline and 2 weeks

InterventionLiter (Least Squares Mean)
Placebo-0.023
Olo 2 mcg qd0.062
Olo 5 mcg qd0.099
Olo 10 mcg qd0.102
Olo 20 mcg qd0.105

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Trough FEV1 Response After 1 Week

Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication. (NCT00452400)
Timeframe: Baseline and 1 week

InterventionLiter (Least Squares Mean)
Placebo-0.029
Olo 2 mcg qd0.059
Olo 5 mcg qd0.108
Olo 10 mcg qd0.099
Olo 20 mcg qd0.140

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Peak FVC (0-3h) Response After 4 Weeks

Peak (0-3h) will be the maximum post-dose value during the first 3 hours. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.152
Olo 2 mcg qd0.440
Olo 5 mcg qd0.432
Olo 10 mcg qd0.449
Olo 20 mcg qd0.438

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Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination

Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events. (NCT00452400)
Timeframe: 4 weeks

,,,,
Interventionparticipants (Number)
Electrocardiogram QT prolongedBlood creatine phosphokinase increasedGamma-glutamyltransferase increasedAtrioventricular block first degreeSinus arrhythmiaTachycardiaPalpitations
Olo 10 mcg qd0000010
Olo 2 mcg qd1010001
Olo 20 mcg qd2101000
Olo 5 mcg qd1000010
Placebo0000100

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Peak FEV1 (0-3h) Response After 4 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the 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 baseline, treatment and centre (centre random, all other effects fixed). (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.078
Olo 2 mcg qd0.242
Olo 5 mcg qd0.247
Olo 10 mcg qd0.295
Olo 20 mcg qd0.303

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Peak FEV1 (0-3h) Response At Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the 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 baseline,treatment and centre (centre random, all other effects fixed). (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1

InterventionLiter (Least Squares Mean)
Placebo0.104
Olo 2 mcg qd0.259
Olo 5 mcg qd0.288
Olo 10 mcg qd0.335
Olo 20 mcg qd0.335

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Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)

AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3 at steady state. (NCT00452400)
Timeframe: Baseline and 4 weeks

,,
InterventionPicogram*hours/milliliter (Geometric Mean)
Olodaterol (N=0;0;0;63;70)Olodaterol glucuronide (N=0;0;55;69;63)
Olo 10 mcg qd15.611.4
Olo 20 mcg qd27.723.9
Olo 5 mcg qdNA9.29

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Trough FVC Response After 2 Weeks

Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. (NCT00452400)
Timeframe: Baseline and 2 weeks

InterventionLiter (Least Squares Mean)
Placebo-0.000
Olo 2 mcg qd0.090
Olo 5 mcg qd0.171
Olo 10 mcg qd0.149
Olo 20 mcg qd0.148

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Area Under Curve From 0 to 3 Hours (AUC0-3)

AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3. (NCT00452400)
Timeframe: Baseline and 4 weeks

,
InterventionPicogram*hours/milliliter (Geometric Mean)
Olodaterol (N=0;0;0;29;58)Olodaterol glucuronide (N=0;0;0;44;44)
Olo 10 mcg qd13.311.6
Olo 20 mcg qd20.321.1

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Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)

AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=24 at steady state. (NCT00452400)
Timeframe: Baseline and 4 weeks

,
InterventionPicogram*hours/milliliter (Geometric Mean)
OlodaterolOlodaterol glucuronide
Olo 10 mcg qd104NA
Olo 20 mcg qd145NA

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Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks

Baseline PEFR was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment. (NCT00452400)
Timeframe: 4 weeks

InterventionLiter/minute (Least Squares Mean)
Placebo212.69
Olo 2 mcg qd226.39
Olo 5 mcg qd233.97
Olo 10 mcg qd250.77
Olo 20 mcg qd235.75

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Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks

Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol (albuterol)) (NCT00452400)
Timeframe: 4 weeks

InterventionNumber of puffs (Least Squares Mean)
Placebo2.914
Olo 2 mcg qd2.393
Olo 5 mcg qd3.052
Olo 10 mcg qd1.949
Olo 20 mcg qd2.500

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Weekly Mean Evening PEFR After 4 Weeks

Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment. (NCT00452400)
Timeframe: 4 weeks

InterventionLiter/minute (Least Squares Mean)
Placebo224.65
Olo 2 mcg qd235.09
Olo 5 mcg qd246.98
Olo 10 mcg qd262.88
Olo 20 mcg qd250.06

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Trough FVC Response After 4 Weeks

Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. (NCT00452400)
Timeframe: Baseline and 4 weeks

InterventionLiter (Least Squares Mean)
Placebo-0.026
Olo 2 mcg qd0.068
Olo 5 mcg qd0.136
Olo 10 mcg qd0.146
Olo 20 mcg qd0.153

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Trough FVC Response After 1 Week

Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. (NCT00452400)
Timeframe: Baseline and 1 week

InterventionLiter (Least Squares Mean)
Placebo-0.020
Olo 2 mcg qd0.090
Olo 5 mcg qd0.154
Olo 10 mcg qd0.149
Olo 20 mcg qd0.151

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Trough FEV1 Response After 4 Weeks

Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication. (NCT00452400)
Timeframe: Baseline and 4 weeks

InterventionLiter (Least Squares Mean)
Placebo-0.014
Olo 2 mcg qd0.046
Olo 5 mcg qd0.082
Olo 10 mcg qd0.109
Olo 20 mcg qd0.118

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours postdose using the trapezoidal rule, divided by the observation time (3h) to report in litres. (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1

InterventionLiter (Least Squares Mean)
Placebo0.031
Olo 2 mcg qd0.165
Olo 5 mcg qd0.203
Olo 10 mcg qd0.236
Olo 20 mcg qd0.234

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Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00452400)
Timeframe: Baseline and 1 week

InterventionLiter (Least Squares Mean)
Placebo-0.018
Olo 2 mcg qd0.067
Olo 5 mcg qd0.156
Olo 10 mcg qd0.132
Olo 20 mcg qd0.118

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Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00452400)
Timeframe: Baseline and 2 weeks

InterventionLiter (Least Squares Mean)
Placebo0.006
Olo 2 mcg qd0.059
Olo 5 mcg qd0.135
Olo 10 mcg qd0.105
Olo 20 mcg qd0.098

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Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00452400)
Timeframe: Baseline and 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.005
Olo 2 mcg qd0.058
Olo 5 mcg qd0.134
Olo 10 mcg qd0.145
Olo 20 mcg qd0.094

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Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00452400)
Timeframe: baseline and day1

InterventionLiter (Least Squares Mean)
Placebo0.019
Olo 2 mcg qd0.064
Olo 5 mcg qd0.166
Olo 10 mcg qd0.195
Olo 20 mcg qd0.171

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre 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. (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1

InterventionLiter (Least Squares Mean)
Placebo-0.000
Olo 2 mcg qd0.186
Olo 5 mcg qd0.215
Olo 10 mcg qd0.218
Olo 20 mcg qd0.247

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre 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. (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2

InterventionLiter (Least Squares Mean)
Placebo0.006
Olo 2 mcg qd0.166
Olo 5 mcg qd0.200
Olo 10 mcg qd0.209
Olo 20 mcg qd0.211

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4

InterventionLiter (Least Squares Mean)
Placebo0.013
Olo 2 mcg qd0.154
Olo 5 mcg qd0.175
Olo 10 mcg qd0.226
Olo 20 mcg qd0.228

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Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4

InterventionLiter (Least Squares Mean)
Placebo0.009
Olo 2 mcg qd0.271
Olo 5 mcg qd0.292
Olo 10 mcg qd0.320
Olo 20 mcg qd0.313

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Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)

AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=6 at steady state. (NCT00452400)
Timeframe: Baseline and 4 weeks

,,
InterventionPicogram*hours/milliliter (Geometric Mean)
Olodaterol (N=0;0;0;55;69)Olodaterol glucuronide (N=0;0;32;50;48)
Olo 10 mcg qd29.725.6
Olo 20 mcg qd46.449.4
Olo 5 mcg qdNA21.4

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Laboratory Testing: Average Change From Baseline of Potassium

Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value. (NCT00452400)
Timeframe: Baseline and day 29

Interventionmmol/L (Geometric Mean)
Placebo0.97
Olo 2 mcg qd0.99
Olo 5 mcg qd0.98
Olo 10 mcg qd0.97
Olo 20 mcg qd0.98

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Peak FEV1 (0-3h) Response After 1 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the 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 baseline, treatment and centre (centre random, all other effects fixed). (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week

InterventionLiter (Least Squares Mean)
Placebo0.062
Olo 2 mcg qd0.264
Olo 5 mcg qd0.293
Olo 10 mcg qd0.295
Olo 20 mcg qd0.321

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Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)

tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. (NCT00452400)
Timeframe: Baseline and 4 weeks

,,
Interventionhours (Median)
Olodaterol (N=0;0;46;72;72)Olodaterol glucuronide (N=0;0;60;72;66)
Olo 10 mcg qd0.2003.00
Olo 20 mcg qd0.2003.00
Olo 5 mcg qd0.1923.00

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Peak FEV1 (0-3h) Response After 2 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the 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 baseline, treatment and centre (centre random, all other effects fixed). (NCT00452400)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

InterventionLiter (Least Squares Mean)
Placebo0.079
Olo 2 mcg qd0.243
Olo 5 mcg qd0.267
Olo 10 mcg qd0.282
Olo 20 mcg qd0.280

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Maximum Concentration at Steady State (Cmax,ss)

Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state. (NCT00452400)
Timeframe: Baseline and 4 weeks

,,
InterventionPicogram/milliliter (Geometric Mean)
Olodaterol (N=0;0;46;72;72)Olodaterol glucuronide (N=0;0;60;72;66)
Olo 10 mcg qd7.135.55
Olo 20 mcg qd14.111.1
Olo 5 mcg qd4.024.90

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Maximum Concentration (Cmax)

Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma. (NCT00452400)
Timeframe: Baseline and 4 weeks

,,
InterventionPicogram/milliliter (Geometric Mean)
Olodaterol (N=0;0;40;71;69)Olodaterol glucuronide (N=0;0;54;71;66)
Olo 10 mcg qd5.455.24
Olo 20 mcg qd12.210.6
Olo 5 mcg qd3.583.94

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. 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. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Day 1

InterventionLiter (Least Squares Mean)
Placebo0.092
Olo 2 mcg qd0.271
Olo 5 mcg qd0.275
Olo 10 mcg qd0.265
Olo 20 mcg qd0.383

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. 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. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1

InterventionLiter (Least Squares Mean)
Placebo0.062
Olo 2 mcg qd0.252
Olo 5 mcg qd0.258
Olo 10 mcg qd0.219
Olo 20 mcg qd0.325

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. 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. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 4

InterventionLiter (Least Squares Mean)
Placebo0.092
Olo 2 mcg qd0.271
Olo 5 mcg qd0.224
Olo 10 mcg qd0.192
Olo 20 mcg qd0.332

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4

InterventionLiter (Least Squares Mean)
Placebo0.091
Olo 2 mcg qd0.269
Olo 5 mcg qd0.229
Olo 10 mcg qd0.190
Olo 20 mcg qd0.323

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 6-12 h (AUC 6-12h) Response at Week 4

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres. (NCT00467740)
Timeframe: 1 hour (h) prior to dose on first day of randomized treatment (baseline) and 1h, 3h, 6h, 9h, 12h relative to dose at Week 4

InterventionLiter (Least Squares Mean)
Placebo0.054
Olo 2 mcg qd0.107
Olo 5 mcg qd0.098
Olo 10 mcg qd0.092
Olo 20 mcg qd0.216

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Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4

InterventionLiter (Least Squares Mean)
Placebo0.076
Olo 2 mcg qd0.159
Olo 5 mcg qd0.154
Olo 10 mcg qd0.113
Olo 20 mcg qd0.267

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Laboratory Testing: Average Change From Baseline of Potassium

Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value. (NCT00467740)
Timeframe: Baseline and 29 days

Interventionmmol/L (Geometric Mean)
Placebo0.98
Olo 2 mcg qd0.97
Olo 5 mcg qd1.00
Olo 10 mcg qd0.99
Olo 20 mcg qd0.97

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Peak FEV1 (0-3h) Response After 1 Week

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week

InterventionLiter (Least Squares Mean)
Placebo0.170
Olo 2 mcg qd0.343
Olo 5 mcg qd0.355
Olo 10 mcg qd0.308
Olo 20 mcg qd0.407

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Peak FEV1 (0-3h) Response After 2 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

InterventionLiter (Least Squares Mean)
Placebo0.182
Olo 2 mcg qd0.386
Olo 5 mcg qd0.335
Olo 10 mcg qd0.261
Olo 20 mcg qd0.403

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Peak FVC (0-3h) Response After 1 Week

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 weeks

InterventionLiter (Least Squares Mean)
Placebo0.182
Olo 2 mcg qd0.281
Olo 5 mcg qd0.301
Olo 10 mcg qd0.259
Olo 20 mcg qd0.367

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Peak FEV1 (0-3h) Response After 4 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.198
Olo 2 mcg qd0.363
Olo 5 mcg qd0.315
Olo 10 mcg qd0.279
Olo 20 mcg qd0.430

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Weekly Mean Evening PEFR After 4 Weeks

Response was defined as change from baseline. Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment. (NCT00467740)
Timeframe: Baseline and 4 weeks

InterventionLiter/minute (Least Squares Mean)
Placebo384.08
Olo 2 mcg qd407.05
Olo 5 mcg qd408.68
Olo 10 mcg qd420.88
Olo 20 mcg qd426.58

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Trough FVC Response After 4 Weeks

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 at the end of the dosing interval. (NCT00467740)
Timeframe: Baseline and 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.018
Olo 2 mcg qd0.055
Olo 5 mcg qd0.076
Olo 10 mcg qd0.042
Olo 20 mcg qd0.166

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Trough FVC Response After 2 Weeks

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 at the end of the dosing interval. (NCT00467740)
Timeframe: Baseline and 2 weeks

InterventionLiter (Least Squares Mean)
Placebo-0.029
Olo 2 mcg qd0.098
Olo 5 mcg qd0.069
Olo 10 mcg qd-0.002
Olo 20 mcg qd0.100

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Trough FVC Response After 1 Week

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 at the end of the dosing interval. (NCT00467740)
Timeframe: Baseline and 1 week

InterventionLiter (Least Squares Mean)
Placebo0.001
Olo 2 mcg qd0.053
Olo 5 mcg qd0.044
Olo 10 mcg qd0.070
Olo 20 mcg qd0.131

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Trough FEV1 Response After 4 Weeks

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 at the end of the dosing interval. (NCT00467740)
Timeframe: Baseline and 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.004
Olo 2 mcg qd0.083
Olo 5 mcg qd0.090
Olo 10 mcg qd0.080
Olo 20 mcg qd0.150

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Trough FEV1 Response After 2 Weeks

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 at the end of the dosing interval. (NCT00467740)
Timeframe: Baseline and 2 weeks

InterventionLiter (Least Squares Mean)
Placebo-0.009
Olo 2 mcg qd0.094
Olo 5 mcg qd0.080
Olo 10 mcg qd0.034
Olo 20 mcg qd0.131

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Trough FEV1 Response After 1 Week

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 at the end of the dosing interval. (NCT00467740)
Timeframe: Baseline and 1 week

InterventionLiter (Least Squares Mean)
Placebo-0.007
Olo 2 mcg qd0.060
Olo 5 mcg qd0.094
Olo 10 mcg qd0.106
Olo 20 mcg qd0.166

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Total Score in Asthma Control Questionnaire After 4 Weeks

Adequacy of asthma control was assessed using a scale of: 0=totally controlled, to 6=Severely uncontrolled. (NCT00467740)
Timeframe: 4 weeks

Interventionunits on a scale (Least Squares Mean)
Placebo1.456
Olo 2 mcg qd1.314
Olo 5 mcg qd1.260
Olo 10 mcg qd1.129
Olo 20 mcg qd1.181

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PEFR Variability After 4 Weeks

PEFR variability represents the absolute difference between the highest morning PEFR value and the highest evening PEFR value of 1 day, divided by the arithmetic mean of these 2 PEFR values and expressed as a percent, weekly means. (NCT00467740)
Timeframe: 4 weeks

Interventionpercentage of PEFR (Least Squares Mean)
Placebo11.694
Olo 2 mcg qd10.575
Olo 5 mcg qd9.343
Olo 10 mcg qd8.649
Olo 20 mcg qd8.756

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Peak FEV1 (0-3h) Response At Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1

InterventionLiter (Least Squares Mean)
Placebo0.203
Olo 2 mcg qd0.372
Olo 5 mcg qd0.378
Olo 10 mcg qd0.376
Olo 20 mcg qd0.499

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Peak FVC (0-3h) Response After 4 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks

InterventionLiter (Least Squares Mean)
Placebo0.199
Olo 2 mcg qd0.274
Olo 5 mcg qd0.267
Olo 10 mcg qd0.235
Olo 20 mcg qd0.439

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Peak FVC (0-3h) Response After 2 Weeks

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

InterventionLiter (Least Squares Mean)
Placebo0.184
Olo 2 mcg qd0.327
Olo 5 mcg qd0.290
Olo 10 mcg qd0.234
Olo 20 mcg qd0.361

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Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks

Weekly mean number of occasions of rescue therapy used per day (prn salbutamol [albuterol]) as assessed by the e-Diary (e-Diary incorporated in AM2+). (NCT00467740)
Timeframe: 4 weeks

InterventionNumber of Puffs (Least Squares Mean)
Placebo1.449
Olo 2 mcg qd1.162
Olo 5 mcg qd0.923
Olo 10 mcg qd1.117
Olo 20 mcg qd0.856

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Weekly Mean Pre-dose Morning PEFR After 4 Weeks

Response was defined as change from baseline. Baseline peak expiratory flow response (PEFR) was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment. (NCT00467740)
Timeframe: Baseline and 4 weeks

InterventionLiter/minute (Least Squares Mean)
Placebo368.18
Olo 2 mcg qd384.42
Olo 5 mcg qd396.06
Olo 10 mcg qd404.26
Olo 20 mcg qd411.13

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Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)

AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=24 at steady state. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration

,
InterventionPicogram*hours/milliliter (Geometric Mean)
OlodaterolOlodaterol glucuronide
Olo 10 mcg qd83.7NA
Olo 20 mcg qd147NA

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Area Under Curve From 0 to 3 Hours (AUC0-3)

AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3 (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration

,
InterventionPicogram*hours/milliliter (Geometric Mean)
Olodaterol (N=0;0;0;20;44)Olodaterol glucuronide (N=0;0;0;28;36)
Olo 10 mcg qd11.89.14
Olo 20 mcg qd17.820.3

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. 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. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2

InterventionLiter (Least Squares Mean)
Placebo0.084
Olo 2 mcg qd0.298
Olo 5 mcg qd0.240
Olo 10 mcg qd0.172
Olo 20 mcg qd0.311

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Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)

AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=3 at steady state. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration

,,
InterventionPicogram*hours/milliliter (Geometric Mean)
Olodaterol (N=0;0;0;38;53)Olodaterol glucuronide (N=0;0;38;44;54)
Olo 10 mcg qd13.09.04
Olo 20 mcg qd25.519.0
Olo 5 mcg qdNA7.71

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Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)

AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma from 0 to time t=6 at steady state. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration

,,
InterventionPicogram*hours/milliliter (Geometric Mean)
Olodaterol (N=0;0;0;32;50)Olodaterol glucuronide (N=0;0;21;23;33)
Olo 10 mcg qd25.321.3
Olo 20 mcg qd46.337.6
Olo 5 mcg qdNA19.2

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Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination

Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events. (NCT00467740)
Timeframe: 4 weeks

,,,,
Interventionparticipants (Number)
PalpitationsVentricular extrasystolesBlood creatine phosphokinase increased
Olo 10 mcg qd000
Olo 2 mcg qd000
Olo 20 mcg qd201
Olo 5 mcg qd110
Placebo000

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Peak FVC (0-3h) Response At Day 1

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. (NCT00467740)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 weeks

InterventionLiter (Least Squares Mean)
Placebo0.218
Olo 2 mcg qd0.297
Olo 5 mcg qd0.315
Olo 10 mcg qd0.315
Olo 20 mcg qd0.398

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Maximum Concentration at Steady State (Cmax,ss)

Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration

,,
InterventionPicogram/milliliter (Geometric Mean)
Olodaterol N=(0;0;39;45;56)Olodaterol glucuronide N=(0;0;46;46;54)
Olo 10 mcg qd5.095.04
Olo 20 mcg qd12.19.19
Olo 5 mcg qd3.194.16

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Time From Dosing to the Maximum Concentration (Tmax)

tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration

,,
Interventionhours (Median)
Olodaterol (N=0;0;21;44;58)Olodaterol glucuronide (N=0;0;38;54;57)
Olo 10 mcg qd0.2342.97
Olo 20 mcg qd0.2672.97
Olo 5 mcg qd0.1832.97

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Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)

tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma at steady state. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h), 3h and 6h after drug administration

,,
Interventionhours (Median)
Olodaterol (N=0;0;39;45;56)Olodaterol glucuronide (N=0;0;46;46;54)
Olo 10 mcg qd0.3333.00
Olo 20 mcg qd0.3332.97
Olo 5 mcg qd0.3333.00

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Maximum Concentration (Cmax)

Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide (a metabolite of olodaterol) in plasma. (NCT00467740)
Timeframe: 30 minutes (mins) before drug administration and 5mins, 10mins, 20mins, 40mins, 1 hour (h) and 3h after drug administration

,,
InterventionPicogram/milliliter (Geometric Mean)
Olodaterol (N=0;0;21;44;58)Olodaterol glucuronide (N=0;0;38;54;57)
Olo 10 mcg qd4.635.00
Olo 20 mcg qd8.249.54
Olo 5 mcg qd3.543.57

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PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment

"PEF (peak expiratory flow rate L/min) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks

,,,
InterventionL/min (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium29.26130.13927.51228.396
Tiotropium+Olodaterol 5/10 μg41.85247.92445.79847.289
Tiotropium+Olodaterol 5/2 μg41.83847.62542.17941.502
Tiotropium+Olodaterol 5/5 μg45.17948.50352.24948.212

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PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.

"PEF (peak expiratory flow rate L/min) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) will be calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres/min. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks

,,,
InterventionL/min (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium21.97329.70132.10829.734
Tiotropium+Olodaterol 5/10 μg40.02753.44854.28956.688
Tiotropium+Olodaterol 5/2 μg35.73852.81654.52752.091
Tiotropium+Olodaterol 5/5 μg35.35049.72253.82948.503

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PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment

"PEF (peak expiratory flow rate L/min) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium43.05147.81948.12947.104
Tiotropium+Olodaterol 5/10 μg62.36073.82873.88676.461
Tiotropium+Olodaterol 5/2 μg53.80169.79279.89070.519
Tiotropium+Olodaterol 5/5 μg53.85369.25471.91665.800

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Physician's Global Evaluation

"Measured a 8-point scale, from 1 (poor) to 8 (excellent), as judged by the physician, over 4 weeks of treatment.~The physician made a global evaluation at the end of the Baseline Period (Test Day 1) and at each visit thereafter. These assessments were made prior to pulmonary function testing and reflected the physician's opinion of the patient's overall clinical condition. This evaluation was based on the need for concomitant medication, number and severity of COPD exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, and other relevant clinical observations.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: 1 week, 2 weeks and 4 weeks

,,,
Interventionunits on a scale (Least Squares Mean)
Day 8Day 15Day 29
5 µg Tiotropium5.1395.2725.264
Tiotropium+Olodaterol 5/10 μg5.1495.1045.252
Tiotropium+Olodaterol 5/2 μg5.1025.1305.295
Tiotropium+Olodaterol 5/5 μg5.1855.3825.447

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Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.

"Trough FEV1 (forced expiratory volume in 1 second) was defined as the mean of the 2 FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 15." (NCT00696020)
Timeframe: Baseline, 1 week and 2 weeks

,,,
InterventionL (Least Squares Mean)
Day 8Day 15
5 µg Tiotropium0.0930.099
Tiotropium+Olodaterol 5/10 μg0.1660.154
Tiotropium+Olodaterol 5/2 μg0.1490.141
Tiotropium+Olodaterol 5/5 μg0.1540.159

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Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment

"Trough FVC (forced vital capacity) was defined as the mean of the 2 FVC values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FVC response was defined as the change from baseline in trough FVC. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: Baseline, 1 week, 2 weeks and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 8Day 15Day 29
5 µg Tiotropium0.1560.1710.189
Tiotropium+Olodaterol 5/10 μg0.2750.2850.306
Tiotropium+Olodaterol 5/2 μg0.2150.1960.191
Tiotropium+Olodaterol 5/5 μg0.2650.2800.288

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Weekly Mean Evening PEF [L/Min]

"The patient will record twice daily peak flow measurements using an AM2+ device. The evening measurement will be performed at bedtime.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: Throughout the 4 weeks treatment period

,,,
InterventionL/min (Mean)
Week 1Week 2Week 3Week 4
5 µg Tiotropium249.10247.10249.78246.77
Tiotropium+Olodaterol 5/10 μg268.58266.40265.67265.50
Tiotropium+Olodaterol 5/2 μg260.86260.73258.20253.12
Tiotropium+Olodaterol 5/5 μg267.47267.31268.16266.61

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Weekly Mean Pre-dose Morning PEF [L/Min]

"The patient will record twice daily peak flow measurements using an Asthma Monitor®Am2+ (AM2+) device. Morning measurements will be performed immediately upon arising after the patient has cleared out mucus, prior to administration of trial and/or rescue medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: Throughout the 4 week treatment period

,,,
InterventionL/min (Least Squares Mean)
Week 1Week 2Week 3Week 4
5 µg Tiotropium227.81228.57228.82226.49
Tiotropium+Olodaterol 5/10 μg248.76247.77248.33247.30
Tiotropium+Olodaterol 5/2 μg244.43240.87239.61234.14
Tiotropium+Olodaterol 5/5 μg248.84249.99249.39249.17

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Tmax,ss Olodaterol [h]

"Time from last dosing to maximum concentration of Olodaterol in plasma at steady state (tmax,ss) after 4 weeks treatment.~No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure." (NCT00696020)
Timeframe: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Interventionhours (Median)
Tiotropium+Olodaterol 5/5 μg0.167
Tiotropium+Olodaterol 5/10 μg0.183

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Weekly Mean Number of Occasions of Rescue Therapy Used Per Day

The means are adjusted, Based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed). (NCT00696020)
Timeframe: Throughout the 4 weeks treatment period

,,,
Interventionoccasion(s) (Least Squares Mean)
Week 1Week 2Week 3Week 4
5 µg Tiotropium1.9051.7841.9472.017
Tiotropium+Olodaterol 5/10 μg1.6691.4771.5631.482
Tiotropium+Olodaterol 5/2 μg1.5121.6101.6501.615
Tiotropium+Olodaterol 5/5 μg1.5041.4761.4921.602

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Tmax,ss Tiotropium [h]

Time from last dosing to maximum concentration of Tiotropium in plasma at steady state (tmax,ss) after 4 weeks of treatment. (NCT00696020)
Timeframe: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Interventionhours (Median)
5 µg Tiotropium0.133
Tiotropium+Olodaterol 5/2 μg0.100
Tiotropium+Olodaterol 5/5 μg0.083
Tiotropium+Olodaterol 5/10 μg0.133

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Trough FEV1 Response [L] After 4 Weeks of Treatment

"Trough FEV1 (Forced expiratory volume in 1 second) was defined as the mean of the two FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: Baseline and 4 weeks

InterventionL (Least Squares Mean)
5 µg Tiotropium0.110
Tiotropium+Olodaterol 5/2 μg0.134
Tiotropium+Olodaterol 5/5 μg0.143
Tiotropium+Olodaterol 5/10 μg0.168

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FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment

"FEV1 (forced expiratory volume in 1 second) AUC(6-12h) response is defined as change from the baseline value. AUC(6-12h) will be calculated as the area under the curve from 6 to 12 hours on the various test days using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium0.1430.1690.1420.145
Tiotropium+Olodaterol 5/10 μg0.1750.1720.1690.180
Tiotropium+Olodaterol 5/2 μg0.1810.2030.1970.189
Tiotropium+Olodaterol 5/5 μg0.2090.2190.2050.193

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FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment

"Response is defined as change from the baseline value. AUC(0-3h) (area under the curve) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium0.1610.2040.2010.191
Tiotropium+Olodaterol 5/10 μg0.2250.3150.3090.316
Tiotropium+Olodaterol 5/2 μg0.2010.2890.2880.276
Tiotropium+Olodaterol 5/5 μg0.2290.3020.3050.270

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FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment

"FEV1 (forced expiratory volume in 1 second) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium0.2490.2760.2760.266
Tiotropium+Olodaterol 5/10 μg0.3210.3970.3860.410
Tiotropium+Olodaterol 5/2 μg0.2840.3590.3610.353
Tiotropium+Olodaterol 5/5 μg0.3110.3780.3910.348

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FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.

"FVC (forced vital capacity) AUC(0-3h) response is defined as change from the baseline value. AUC(0-3h) was calculated as the area under the curve from 0 to 3 hours on the various test days using the trapezoidal rule, divided by the full duration (3 hours) to report in litres. Baseline FVC was defined as the mean of the 2 pre-treatment FVC values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium0.2680.3100.3270.308
Tiotropium+Olodaterol 5/10 μg0.4100.5370.5540.547
Tiotropium+Olodaterol 5/2 μg0.3310.4410.4370.424
Tiotropium+Olodaterol 5/5 μg0.4130.4930.5130.492

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FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment

"FVC (forced vital capacity) peak(0-3h) is the maximum post-dose value during the first 3 hours after first administration and after 1, 2 and 4 weeks of treatment. Response is defined as change from the baseline value. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed).~Comparisons between groups are presented for Day 29." (NCT00696020)
Timeframe: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks

,,,
InterventionL (Least Squares Mean)
Day 1Day 8Day 15Day 29
5 µg Tiotropium0.4280.4370.4650.431
Tiotropium+Olodaterol 5/10 μg0.5830.6900.6970.696
Tiotropium+Olodaterol 5/2 μg0.4760.5600.5860.562
Tiotropium+Olodaterol 5/5 μg0.5760.6150.6480.634

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PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment

"PEF (peak expiratory flow rate L/min) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)

InterventionL (Least Squares Mean)
5 µg Tiotropium30.576
Tiotropium+Olodaterol 5/2 μg53.443
Tiotropium+Olodaterol 5/5 μg50.319
Tiotropium+Olodaterol 5/10 μg58.368

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Patient's Global Rating

"Patient's Global Rating at the end of the 4 week treatment period.~Patients rated their health (respiratory condition) at Day 29 (compared to the day before they commenced treatment with study medication) on a 7-point scale as very much better (1), much better (2), a little better (3), no change (4), a little worse (5), much worse (6), or very much worse (7). The assessment was made prior to pulmonary function testing and all other study procedures. The Patient's Global Rating was also completed before the Physician's Global Evaluation.~The means are adjusted, based on an ANCOVA with terms for treatment, centre (centre random, treatment effect fixed)." (NCT00696020)
Timeframe: 4 weeks

Interventionunits on a patient's global rating score (Least Squares Mean)
5 µg Tiotropium2.866
Tiotropium+Olodaterol 5/2 μg2.598
Tiotropium+Olodaterol 5/5 μg2.368
Tiotropium+Olodaterol 5/10 μg2.377

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FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment

"FVC (forced vital capacity) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on an ANCOVA with terms for baseline, treatment, centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)

InterventionL (Least Squares Mean)
5 µg Tiotropium0.309
Tiotropium+Olodaterol 5/2 μg0.429
Tiotropium+Olodaterol 5/5 μg0.492
Tiotropium+Olodaterol 5/10 μg0.547

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FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment

"FEV1 (forced expiratory volume in 1 second) AUC(0-6h) response is defined as change from the baseline value. AUC(0-6h) will be calculated as the area under the curve from 0 to 6 hours on test day 29 using the trapezoidal rule, divided by the full duration (6 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication.~The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed)." (NCT00696020)
Timeframe: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)

InterventionL (Least Squares Mean)
5 µg Tiotropium0.194
Tiotropium+Olodaterol 5/2 μg0.282
Tiotropium+Olodaterol 5/5 μg0.280
Tiotropium+Olodaterol 5/10 μg0.322

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Cmax,ss Tiotropium [pg/mL]

Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss) after 4 weeks treatment. (NCT00696020)
Timeframe: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Interventionpg/mL (Geometric Mean)
5 µg Tiotropium13.3
Tiotropium+Olodaterol 5/2 μg13.9
Tiotropium+Olodaterol 5/5 μg12.4
Tiotropium+Olodaterol 5/10 μg14.4

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Cmax,ss Olodaterol [pg/mL]

"Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss) after 4 weeks of treatment.~No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure." (NCT00696020)
Timeframe: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Interventionpg/mL (Geometric Mean)
Tiotropium+Olodaterol 5/5 μg4.39
Tiotropium+Olodaterol 5/10 μg6.87

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Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities

"Possible clinically significant anormalities (laboratory data); marked changes from baseline for vital signs, notable change in ECG and new onset of ECG abnormalities. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AEs).~All AEs with an onset after the first dose of study medication up to 21 days after the last dose of study medication were to have been assigned to the Treatment Period." (NCT00696020)
Timeframe: From first dose up to 21 days after last dose of study medication.

Interventionparticipants (Number)
5 µg Tiotropium1
Tiotropium+Olodaterol 5/2 μg0
Tiotropium+Olodaterol 5/5 μg0
Tiotropium+Olodaterol 5/10 μg0

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AUC(0-3h,ss) Tiotropium [pg*h/mL]

Area under the concentration-time curve of Tiotropium at steady state (AUC(0-3h,ss)) from 0 to 3 hours post dosing after 4 weeks of treatment. (NCT00696020)
Timeframe: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Interventionpg*h/mL (Geometric Mean)
5 µg Tiotropium21.8
Tiotropium+Olodaterol 5/2 μg21.9
Tiotropium+Olodaterol 5/5 μg21.9
Tiotropium+Olodaterol 5/10 μg21.0

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AUC(0-1h,ss) Olodaterol [pg*h/mL]

"Area under the concentration-time curve of Olodaterol in plasma at steady state (AUC(0-1h,ss)) from 0 to 1 hour post dosing after 4 weeks of treatment.~No results displayed for Tiotropium+Olodaterol 5/2 μg because there were zero total participants analyzed for this outcome measure." (NCT00696020)
Timeframe: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/5 μg3.97
Tiotropium+Olodaterol 5/10 μg5.82

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Clinically Significant Abnormalities for Blood Chemistry, Haematology, Urinalysis and Physical Examination

Clinically significant abnormalities for blood chemistry, haematology, urinalysis and physical examination (NCT00720499)
Timeframe: 14 weeks

,
Interventionparticipants (Number)
Creatinine phosphokinase increasedEosinophils increasedUrinalysis
Olo 2 µg + Tio 5 µg830
Olo 5 µg + Tio 5 µg730

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12-lead ECG QTcF Intervals

"12-lead ECG corrected heart rate (QT) interval, using Fridericia method (QTcF), baseline and change from baseline at other time points in milliseconds.~Statistics for each planned time from baseline to day 29." (NCT00720499)
Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

,
InterventionmS (Mean)
BaselineDay1 0:10Day1 1:00 (N=138, 138)Day15 -0:30 (N=137, 137)Day15 0:10 (N=135, 136)Day29 -0:30 (N=134, 136)Day29 0:10 (N=132, 135)Day29 1:00 (N=132, 135)
Olo 2 µg + Tio 5 µg405.63-0.89-0.690.55-1.16-1.35-1.22-0.56
Olo 5 µg + Tio 5 µg403.530.97-0.61-0.03-1.02-0.24-2.08-1.05

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12-lead ECG QTcB Intervals

"12-lead ECG heart rate corrected QT interval, using Bazett method (QTcB), baseline and change from baseline at other time points in milliseconds.~Statistics for each planned time from baseline to day 29." (NCT00720499)
Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

,
InterventionmS (Mean)
BaselineDay1 0:10Day1 1:00 (N=138, 138)Day15 -0:30 (N=137, 137)Day15 0:10 (N=135, 136)Day29 -0:30 (N=134, 136)Day29 0:10 (N=132, 135)Day29 1:00 (N=132, 135)
Olo 2 µg + Tio 5 µg418.12-2.18-2.570.93-2.51-1.87-3.13-2.55
Olo 5 µg + Tio 5 µg415.560.05-2.20.91-1.761.43-2.33-1.69

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12-lead ECG QT Intervals

"12-lead ECG QT intervals baseline and change from baseline at other time points in milliseconds.~Statistics for each planned time from baseline to day 29." (NCT00720499)
Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

,
InterventionmS (Mean)
BaselineDay1 0:10Day1 1:00 (N=138, 138)Day15 -0:30 (N=137, 137)Day15 0:10 (N=135, 136)Day29 -0:30 (N=134, 136)Day29 0:10 (N=132, 135)Day29 1:00 (N=132, 135)
Olo 2 µg + Tio 5 µg382.731.592.97-0.091.44-0.592.273.14
Olo 5 µg + Tio 5 µg381.332.692.33-1.760.53-3.14-1.730.2

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12-lead ECG QRS Intervals

"12-lead ECG QRS intervals baseline and change from baseline at other time points in milliseconds~Statistics for each planned time from baseline to day 29." (NCT00720499)
Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

,
InterventionmS (Mean)
BaselineDay1 0:10Day1 1:00Day15 -0:30 (N=137, 137)Day15 0:10 (N=135, 136)Day29 -0:30 (N=134, 136)Day29 0:10 (N=132, 135)Day29 1:00 (N=132, 135)
Olo 2 µg + Tio 5 µg92.71-0.28-0.47-0.55-0.67-0.44-1.27-0.33
Olo 5 µg + Tio 5 µg92.41-0.650.31-0.44-0.32-0.75-0.82-0.39

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12-lead ECG PR Intervals

"12-lead ECG PR intervals baseline and change from baseline at other timepoints in milliseconds.~Statistics for each planned time from baseline to day 29." (NCT00720499)
Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

,
InterventionmS (Mean)
BaselineDay1 0:10Day1 1:00 (N=139, 137)Day15 -0:30 (N=136, 137)Day15 0:10 (N=135, 136)Day29 -0:30 (N=134, 135)Day29 0:10 (N=132, 135)Day29 1:00 (N=132, 135)
Olo 2 µg + Tio 5 µg160.03-1.022.120.550.28-1.29-0.291.98
Olo 5 µg + Tio 5 µg160.69-1.860.09-0.95-1.24-0.19-2.050.22

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12-lead ECG Heart Rate

"12-lead Electrocardiogram (ECG) Heart rate baseline and change from baseline values at other time points in Beats Per Minute (BPM)~Statistics for each planned time from baseline to day 29." (NCT00720499)
Timeframe: Baseline, then 10min, 1h after drug administration on day 1, 30min before and 10min after drug administration on day 15, in addition 1h after drug administration on day 29

,
InterventionBPM (Mean)
BaselineDay1 0:10Day1 1:00Day15 -0:30 (N=137, 137)Day15 0:10 (N=135, 136)Day29 -0:30 (N=134, 136)Day29 0:10 (N=132, 135)Day29 1:00 (N=132, 135)
Olo 2 µg + Tio 5 µg72.96-1.44-2.090.42-1.61-0.69-2.14-2.34
Olo 5 µg + Tio 5 µg72.38-1.01-1.61.1-0.791.68-0.24-0.73

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PEFR Peak 0-3h Response

"PEFR peak 0-3h response [L/min] on days 1, 15 and 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

,
InterventionLitres / minute (Mean)
Day 1Day 15Day 29
Olo 2 µg + Tio 5 µg49.12546.35552.497
Olo 5 µg + Tio 5 µg48.94652.83555.596

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PEFR AUC (0-3h) Response

"Peak Expiratory Flow Rate (PEFR) AUC (0-3h) response [L/min] on days 1, 15 and 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

,
InterventionLitres / minute (Mean)
Day 1Day 15Day 29
Olo 2 µg + Tio 5 µg27.15927.81732.395
Olo 5 µg + Tio 5 µg28.14334.12833.947

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Overall Marked Changes From Baseline in Vital Signs

Overall marked changes from baseline in systolic blood pressure, diastolic blood pressure and pulse rate. (NCT00720499)
Timeframe: Baseline to week 14

,
Interventionparticipants (Number)
Systolic blood pressure increasedSystolic blood pressure decreasedDiastolic blood pressure increasedDiastolic blood pressure decreasedPulse rate increasedPulse rate decreased
Olo 2 µg + Tio 5 µg161019131019
Olo 5 µg + Tio 5 µg231115171310

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Individual FVC Measurements

"Individual FVC measurements [L] at each time point~The categories correspond to the planned times for FVC measurements on Day 29.~The presented means are adjusted." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

,
InterventionLitres (Mean)
-1:00-0:100:050:301:002:003:004:005:006:00
Olo 2 µg + Tio 5 µg2.8942.8923.0093.0673.0933.1543.1473.1433.1093.061
Olo 5 µg + Tio5 µg2.8992.9073.0323.0833.1123.1893.2013.2043.1313.083

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Individual FEV1 Measurements

"Individual FEV1 measurements [L] at each time point on Day 29.~The presented means are adjusted." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

,
InterventionLitres (Mean)
-1:00-0:100:050:301:002:003:004:005:006:00
Olo 2 µg + Tio 5 µg1.4261.4341.4971.5411.5701.6171.6011.5821.5711.547
Olo 5 µg + Tio5 µg1.4171.4381.4981.5341.5701.6141.6061.6061.5701.551

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Trough Forced Expiratory Volume in One Second (FEV1) Response [L] After Four Weeks of Treatment.

"Trough FEV1 was defined as the mean of the 2 FEV1 values at the end of the dosing interval, 24 hours post-drug administration.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1 hour (h), 10 minutes (min) before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

InterventionLitres (Mean)
Olo 2 µg + Tio 5 µg0.057
Olo 5 µg + Tio5 µg0.055

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Trough FEV1 Response [L] After 2 Weeks of Treatment

"Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15

InterventionLitres (Mean)
Olo 2 µg + Tio 5 µg0.037
Olo 5 µg + Tio5 µg0.059

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FVC AUC (0-3h) Response

"FVC AUC (0-3h) response [L] on days 1, 15 and 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

,
InterventionLitres (Mean)
Day 1Day 15Day 29
Olo 2 µg + Tio 5 µg0.2730.2710.275
Olo 5 µg + Tio5 µg0.2750.3080.303

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FEV1 Peak 0-3h Response

"FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response [L] on days 1, 15 and 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

,
InterventionLitres (Mean)
Day 1Day 15Day 29
Olo 2 µg + Tio 5 µg0.2690.2570.288
Olo 5 µg + Tio5 µg0.2620.2790.294

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FEV1 AUC 0-3h, Response

"FEV1 Area Under the Curve (AUC) 0-3h, response [L] on days 1, 15 and 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on days 1, 15 and 29

,
InterventionLitres (Mean)
Day 1Day 15Day 29
Olo 2 µg + Tio 5 µg0.1680.1740.201
Olo 5 µg + Tio5 µg0.1730.1940.200

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Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (PRN Salbutamol [Albuterol])

"Weekly mean number of occasions of rescue therapy used per day (as occasion require (PRN) salbutamol [albuterol]) on weeks 1,2,3 and 4.~The means presented are the adjusted mean of weekly mean." (NCT00720499)
Timeframe: Weeks 1,2,3 and 4

,
Interventionnumber of occasions / day (Mean)
Week 1Week 2Week 3Week 4
Olo 2 µg + Tio 5 µg1.2941.4721.3691.403
Olo 5 µg + Tio 5 µg1.3051.3521.3671.363

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Weekly Mean Morning PEFR

"Weekly mean morning PEFR [L/min] on weeks 1,2,3 and 4.~The presented means are adjusted." (NCT00720499)
Timeframe: Weeks 1,2,3 and 4

,
InterventionLitres / minute (Mean)
Week 1Week 2Week 3Week 4
Olo 2 µg + Tio 5 µg244.16242.38242.31242.90
Olo 5 µg + Tio 5 µg245.28243.72242.97244.56

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Weekly Mean Evening PEFR

"Weekly mean evening PEFR [L/min] on weeks 1,2,3 and 4.~The presented means are adjusted." (NCT00720499)
Timeframe: Weeks 1,2,3 and 4

,
InterventionLitres / minute (Mean)
Week 1Week 2Week 3Week 4
Olo 2 µg + Tio 5 µg262.21261.08258.62261.38
Olo 5 µg + Tio 5 µg265.51262.47260.32260.34

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Trough FVC Response

"Trough Forced Vital Capacity (FVC) response [L] on days 15 and 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 15, in addition 4h, 5h, 6h after drug administration on day 29

,
InterventionLitres (Mean)
Day 15Day 29
Olo 2 µg + Tio 5 µg0.0720.066
Olo 5 µg + Tio5 µg0.1040.076

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Physician's Global Evaluation

"Physician's global evaluation score on days 15 and 29~The score was evaluated on a 8-points scale :~Poor : 1,2~Fair : 3,4~Good : 5,6~Excellent : 7,8~The presented means are adjusted" (NCT00720499)
Timeframe: Days 15 and 29

,
Interventionunits on a scale (Mean)
Day 15Day 29
Olo 2 µg + Tio 5 µg5.0845.085
Olo 5 µg + Tio 5 µg5.0795.065

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FEV1 (Unsupervised) AUC (6-12h) Response

"FEV1 (unsupervised) AUC (6-12h) response [L] on day 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 6 hours (h), 9h and 12h after drug administration on day 29

InterventionLitres (Mean)
Olo 2 µg + Tio 5 µg0.106
Olo 5 µg + Tio5 µg0.114

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FEV1, AUC (0-6h) Response

"FEV1, AUC (0-6h) response [L] on day 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

InterventionLitres (Mean)
Olo 2 µg + Tio 5 µg0.202
Olo 5 µg + Tio5 µg0.206

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FVC AUC (0-6h) Response

"FVC AUC (0-6h) response [L] on day 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h, 4h, 5h, 6h after drug administration on day 29

InterventionLitres (Mean)
Olo 2 µg + Tio 5 µg0.283
Olo 5 µg + Tio5 µg0.318

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FVC Peak 0-3h Response

"FVC peak 0-3h response [L] on day 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1h, 10min before drug administration and 5min, 30min, 1h, 2h, 3h after drug administration on day 29

InterventionLitres (Mean)
Olo 2 µg + Tio 5 µg0.444
Olo 5 µg + Tio5 µg0.490

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Patient Global Rating

"Patient global rating scores treatment comparison after 4 weeks~The score was evaluated on a 7-point scale :~1 : very much better~2 : much better~3 : a little better~4 : no change~5 : a little worse~6 : much worse~7 : very much worse~The presented means are adjusted." (NCT00720499)
Timeframe: 4 weeks

Interventionunits on a scale (Mean)
Olo 2 µg + Tio 5 µg3.207
Olo 5 µg + Tio 5 µg3.093

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PEFR AUC (6-12h) Response

"PEFR AUC (6-12h) response [L] on day 29.~Response is defined as the change from baseline, baseline is defined as the mean of the 2 pre-treatment timepoints (-1 hour and -10 minutes) before first drug administration in each treatment period.~The presented means are adjusted based on an ANCOVA with terms for baseline, treatment, centre, patient within centre and period (all effects fixed)." (NCT00720499)
Timeframe: 1 hour (h) and 10 minutes before drug administration on day 1 and 6h, 9h and 12h after drug administration on day 29

InterventionLitres / minute (Mean)
Olo 2 µg + Tio 5 µg24.830
Olo 5 µg + Tio 5 µg24.130

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Peak FEV1 (0-3h) Response After 48 Weeks

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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.029
Olo 5 mcg qd0.198
Olo 10 mcg qd0.192

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Peak FEV1 (0-3h) Response After 6 Weeks

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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.066
Olo 5 mcg qd0.238
Olo 10 mcg qd0.238

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Peak FEV1 (0-3h) Response At Day 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." (NCT00782210)
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 at Day 1

InterventionLiter (Mean)
Placebo0.104
Olo 5 mcg qd0.259
Olo 10 mcg qd0.275

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Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile. (NCT00782210)
Timeframe: Baseline to end of study at 48 weeks.

Interventiondays (Mean)
Placebo (Tiotropium)194.0
Placebo (Non-tiotropium)160.0
Olo 5 mcg qd (Tiotropium)203.0
Olo 5 mcg qd (Non-tiotropium)236.0
Olo 10 mcg qd (Tiotropium)167.0
Olo 10 mcg qd(Non-tiotropium)239.0

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Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization

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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile. (NCT00782210)
Timeframe: Baseline to end of study at 48 weeks.

Interventiondays (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

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Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile. (NCT00782210)
Timeframe: Baseline to end of study at 48 weeks.

Interventiondays (Mean)
Placebo (Tiotropium)194.0
Placebo (Non-tiotropium)216.0
Olo 5 mcg qd (Tiotropium)218.0
Olo 5 mcg qd (Non-tiotropium)344.0
Olo 10 mcg qd (Tiotropium)170.0
Olo 10 mcg qd(Non-tiotropium)309.0

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Trough FEV1 Response After 18 Weeks

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. (NCT00782210)
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 after 18 weeks

InterventionLiter (Mean)
Placebo-0.042
Olo 5 mcg qd0.056
Olo 10 mcg qd0.059

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Trough FEV1 Response After 2 Weeks

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 a -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. (NCT00782210)
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 after 2 weeks

InterventionLiter (Mean)
Placebo-0.019
Olo 5 mcg qd0.076
Olo 10 mcg qd0.091

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Trough FEV1 Response After 24 Weeks

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. (NCT00782210)
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 after 24 weeks

InterventionLiter (Mean)
Placebo-0.050
Olo 5 mcg qd0.036
Olo 10 mcg qd0.039

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Trough FEV1 Response After 32 Weeks

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. (NCT00782210)
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 after 32 weeks

InterventionLiter (Mean)
Placebo-0.051
Olo 5 mcg qd0.041
Olo 10 mcg qd0.034

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Trough FEV1 Response After 40 Weeks

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. (NCT00782210)
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 after 40 weeks

InterventionLiter (Mean)
Placebo-0.061
Olo 5 mcg qd0.046
Olo 10 mcg qd0.044

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Trough FEV1 Response After 48 Weeks

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. (NCT00782210)
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 after 48 weeks

InterventionLiter (Mean)
Placebo-0.74
Olo 5 mcg qd0.019
Olo 10 mcg qd0.017

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Trough FEV1 Response After 6 Weeks

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. (NCT00782210)
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 after 6 weeks

InterventionLiter (Mean)
Placebo-0.022
Olo 5 mcg qd0.073
Olo 10 mcg qd0.069

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Trough FEV1 Response at Day 85 (12 Weeks)

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. (NCT00782210)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85.

InterventionLiter (Mean)
Placebo-0.041
Olo 5 mcg qd0.050
Olo 10 mcg qd0.060

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Trough FVC Response After 12 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 12 weeks

InterventionLiter (Mean)
Placebo-0.030
Olo 5 mcg qd0.085
Olo 10 mcg qd0.130

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Trough FVC Response After 18 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 18 weeks

InterventionLiter (Mean)
Placebo-0.028
Olo 5 mcg qd0.102
Olo 10 mcg qd0.134

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Trough FVC Response After 2 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 2 weeks

InterventionLiter (Mean)
Placebo-0.015
Olo 5 mcg qd0.132
Olo 10 mcg qd0.169

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Trough FVC Response After 24 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 24 weeks

InterventionLiter (Mean)
Placebo-0.028
Olo 5 mcg qd0.055
Olo 10 mcg qd0.096

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Trough FVC Response After 32 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 32 weeks

InterventionLiter (Mean)
Placebo-0.026
Olo 5 mcg qd0.065
Olo 10 mcg qd0.097

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Trough FVC Response After 48 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 48 weeks

InterventionLiter (Mean)
Placebo-0.083
Olo 5 mcg qd0.011
Olo 10 mcg qd0.032

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Trough FVC Response After 6 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 6 weeks

InterventionLiter (Mean)
Placebo-0.005
Olo 5 mcg qd0.125
Olo 10 mcg qd0.135

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Weekly Mean Daily (24h) Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. (NCT00782210)
Timeframe: From Screening to week 48

InterventionNumber of puffs (Mean)
Placebo3.747
Olodaterol (Olo) 5 mcg qd2.642
Olodaterol (Olo) 10 mcg qd2.312

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Weekly Mean Daytime Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. (NCT00782210)
Timeframe: From Screening to week 48

InterventionNumber of puffs (Mean)
Placebo1.487
Olodaterol (Olo) 5 mcg qd0.967
Olodaterol (Olo) 10 mcg qd0.839

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Weekly Mean Evening Peak Expiratory Flow Rate (PEF)

Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded. (NCT00782210)
Timeframe: at bedtime from Screening to week 48

InterventionL/min (Mean)
Placebo190.676
Olodaterol (Olo) 5 mcg qd207.862
Olodaterol (Olo) 10 mcg qd205.236

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Weekly Mean Nighttime Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. (NCT00782210)
Timeframe: From Screening to week 48

InterventionNumber of puffs (Mean)
Placebo2.283
Olodaterol (Olo) 5 mcg qd1.701
Olodaterol (Olo) 10 mcg qd1.492

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Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)

Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded. (NCT00782210)
Timeframe: immediately upon arising (before drug administration) from Screening to week 48

InterventionL/min (Mean)
Placebo180.019
Olodaterol (Olo) 5 mcg qd193.376
Olodaterol (Olo) 10 mcg qd195.475

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Trough FVC Response After 40 Weeks

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 FVCs obtained 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. (NCT00782210)
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 after 40 weeks

InterventionLiter (Mean)
Placebo-0.044
Olo 5 mcg qd0.087
Olo 10 mcg qd0.111

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Change From Baseline in Potassium

Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements. (NCT00782210)
Timeframe: Day 1 and at 12, 24 and 48 weeks

Interventionmmol/L (Mean)
Placebo0.0
Olodaterol (Olo) 5 mcg qd0.0
Olodaterol (Olo) 10 mcg qd0.0

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. 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. (NCT00782210)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)

InterventionLiter (Mean)
Placebo-0.029
Olo 5 mcg qd0.144
Olo 10 mcg qd0.139

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks

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 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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo-0.000
Olo 5 mcg qd0.180
Olo 10 mcg qd0.192

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks

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 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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo-0.18
Olo 5 mcg qd0.156
Olo 10 mcg qd0.143

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks

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 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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo-0.043
Olo 5 mcg qd0.130
Olo 10 mcg qd0.126

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks

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 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. (NCT00782210)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

InterventionLiter (Mean)
Placebo-0.001
Olo 5 mcg qd0.169
Olo 10 mcg qd0.165

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1

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 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. (NCT00782210)
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 at day 1

InterventionLiter (Mean)
Placebo0.024
Olo 5 mcg qd0.189
Olo 10 mcg qd0.199

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)

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. (NCT00782210)
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 Day 85

InterventionLiter (Mean)
Placebo-0.007
Olo 5 mcg qd0.165
Olo 10 mcg qd0.169

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Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FVC 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. (NCT00782210)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)

InterventionLiter (Mean)
Placebo-0.019
Olo 5 mcg qd0.283
Olo 10 mcg qd0.230

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.026
Olo 5 mcg qd0.323
Olo 10 mcg qd0.353

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782210)
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 at Day 1

InterventionLiter (Mean)
Placebo0.063
Olo 5 mcg qd0.350
Olo 10 mcg qd0.392

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.003
Olo 5 mcg qd0.277
Olo 10 mcg qd0.295

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.026
Olo 5 mcg qd0.261
Olo 10 mcg qd0.281

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782210)
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

InterventionLiter (Mean)
Placebo-0.040
Olo 5 mcg qd0.204
Olo 10 mcg qd0.231

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.022
Olo 5 mcg qd0.276
Olo 10 mcg qd0.316

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FVC Peak (0-3h) Response After 12 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.169
Olo 5 mcg qd0.421
Olo 10 mcg qd0.430

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FVC Peak (0-3h) Response After 2 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.207
Olo 5 mcg qd0.471
Olo 10 mcg qd0.499

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FVC Peak (0-3h) Response After 24 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.188
Olo 5 mcg qd0.419
Olo 10 mcg qd0.420

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FVC Peak (0-3h) Response After 48 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.109
Olo 5 mcg qd0.356
Olo 10 mcg qd0.369

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FVC Peak (0-3h) Response After 6 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.180
Olo 5 mcg qd0.430
Olo 10 mcg qd0.460

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FVC Peak (0-3h) Response At Day 1

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782210)
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 at Day 1

InterventionLiter (Mean)
Placebo0.245
Olo 5 mcg qd0.509
Olo 10 mcg qd0.546

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Number of COPD Exacerbations

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. (NCT00782210)
Timeframe: Baseline to end of study at week 48 visit

InterventionNumber of COPD exacerbations (Mean)
Placebo0.7476
Olo 5 mcg qd0.5842
Olo 10 mcg qd0.6322

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Number of COPD Exacerbations Requiring Hospitalization

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. (NCT00782210)
Timeframe: Baseline to end of study at week 48 visit

InterventionNumber of COPD exacerbations (Mean)
Placebo0.1010
Olo 5 mcg qd0.0662
Olo 10 mcg qd0.1133

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Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

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. (NCT00782210)
Timeframe: Baseline to end of study at 48 weeks.

InterventionNumber of COPD exacerbations (Mean)
Placebo0.5745
Olo 5 mcg qd0.4643
Olo 10 mcg qd0.4875

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Patient's Global Rating at Week 12

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782210)
Timeframe: Week 12 visit

InterventionPoint on scale (Mean)
Placebo3.4
Olo 5 mcg qd3.0
Olo 10 mcg qd3.0

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Patient's Global Rating at Week 24

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782210)
Timeframe: Week 24 visit

InterventionPoint on scale (Mean)
Placebo3.5
Olo 5 mcg qd3.0
Olo 10 mcg qd3.0

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Patient's Global Rating at Week 48

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782210)
Timeframe: Week 48 visit

InterventionPoint on scale (Mean)
Placebo3.4
Olo 5 mcg qd3.1
Olo 10 mcg qd3.1

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Patient's Global Rating at Week 6

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782210)
Timeframe: Week 6 visit

InterventionPoint on scale (Mean)
Placebo3.5
Olo 5 mcg qd3.0
Olo 10 mcg qd3.0

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Peak FEV1 (0-3h) Response After 12 Weeks

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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.071
Olo 5 mcg qd0.235
Olo 10 mcg qd0.236

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Peak FEV1 (0-3h) Response After 2 Weeks

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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.077
Olo 5 mcg qd0.254
Olo 10 mcg qd0.267

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Peak FEV1 (0-3h) Response After 24 Weeks

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. (NCT00782210)
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

InterventionLiter (Mean)
Placebo0.055
Olo 5 mcg qd0.230
Olo 10 mcg qd0.206

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FVC Peak (0-3h) Response After 2 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.254
Olo 5 mcg qd0.479
Olo 10 mcg qd0.464

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Peak FEV1 (0-3h) Response After 48 Weeks

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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.041
Olo 5 mcg qd0.197
Olo 10 mcg qd0.198

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Patient's Global Rating at Week 6

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782509)
Timeframe: Week 6 visit

InterventionPoint on scale (Mean)
Placebo3.3
Olo 5 mcg qd3.0
Olo 10 mcg qd2.9

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Trough FVC Response After 12 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 12 weeks

InterventionLiter (Mean)
Placebo0.043
Olo 5 mcg qd0.075
Olo 10 mcg qd0.091

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Trough FEV1 Response at Day 85 (12 Weeks)

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. (NCT00782509)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85.

InterventionLiter (Mean)
Placebo-0.003
Olo 5 mcg qd0.044
Olo 10 mcg qd0.045

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Trough FEV1 Response After 6 Weeks

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. (NCT00782509)
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 after 6 weeks

InterventionLiter (Mean)
Placebo-0.002
Olo 5 mcg qd0.071
Olo 10 mcg qd0.082

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Trough FVC Response After 6 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 6 weeks

InterventionLiter (Mean)
Placebo0.029
Olo 5 mcg qd0.122
Olo 10 mcg qd0.147

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Weekly Mean Evening Peak Expiratory Flow Rate (PEF)

Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded. (NCT00782509)
Timeframe: at bedtime from Screening to week 48

InterventionL/min (Mean)
Placebo195.502
Olo 5 mcg qd207.958
Olo 10 mcg qd216.155

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Weekly Mean of Daily (24h) Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each 24 hour period during week 48. (NCT00782509)
Timeframe: Week 48

InterventionNumber of puffs (Mean)
Placebo3.436
Olo 5 mcg qd2.599
Olo 10 mcg qd2.158

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Weekly Mean of Daily Daytime Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each day during week 48. (NCT00782509)
Timeframe: Week 48

InterventionNumber of puffs (Mean)
Placebo1.363
Olo 5 mcg qd0.947
Olo 10 mcg qd0.850

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Weekly Mean of Daily Nighttime Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each night during week 48. (NCT00782509)
Timeframe: Week 48

InterventionNumber of puffs (Mean)
Placebo2.072
Olo 5 mcg qd1.652
Olo 10 mcg qd1.312

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Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)

Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded. (NCT00782509)
Timeframe: immediately upon arising (before drug administration) from Screening to week 48

InterventionL/min (Mean)
Placebo182.939
Olo 5 mcg qd196.300
Olo 10 mcg qd203.873

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Change From Baseline in Potassium

Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements. (NCT00782509)
Timeframe: Day 1 and at 12, 24 and 48 weeks

Interventionmmol/L (Mean)
Placebo-0.0
Olo 5 mcg qd-0.0
Olo 10 mcg qd0.0

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. 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. (NCT00782509)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)

InterventionLiter (Mean)
Placebo0.010
Olo 5 mcg qd0.120
Olo 10 mcg qd0.100

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks

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 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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.025
Olo 5 mcg qd0.188
Olo 10 mcg qd0.177

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks

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 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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo-0.010
Olo 5 mcg qd0.155
Olo 10 mcg qd0.126

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks

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 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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo-0.030
Olo 5 mcg qd0.132
Olo 10 mcg qd0.128

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks

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 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. (NCT00782509)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

InterventionLiter (Mean)
Placebo0.010
Olo 5 mcg qd0.180
Olo 10 mcg qd0.171

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1

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 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. (NCT00782509)
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 at Day 1

InterventionLiter (Mean)
Placebo0.025
Olo 5 mcg qd0.189
Olo 10 mcg qd0.196

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)

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. (NCT00782509)
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 Day 85

InterventionLiter (Mean)
Placebo0.008
Olo 5 mcg qd0.159
Olo 10 mcg qd0.152

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Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FVC 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. (NCT00782509)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)

InterventionLiter (Mean)
Placebo0.057
Olo 5 mcg qd0.199
Olo 10 mcg qd0.212

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.096
Olo 5 mcg qd0.338
Olo 10 mcg qd0.323

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782509)
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 at Day 1

InterventionLiter (Mean)
Placebo0.052
Olo 5 mcg qd0.383
Olo 10 mcg qd0.384

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.046
Olo 5 mcg qd0.284
Olo 10 mcg qd0.291

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.062
Olo 5 mcg qd0.303
Olo 10 mcg qd0.281

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.053
Olo 5 mcg qd0.271
Olo 10 mcg qd0.271

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.048
Olo 5 mcg qd0.312
Olo 10 mcg qd0.294

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FVC Peak (0-3h) Response After 12 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.213
Olo 5 mcg qd0.439
Olo 10 mcg qd0.422

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Trough FEV1 Response After 48 Weeks

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. (NCT00782509)
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 after 48 weeks

InterventionLiter (Mean)
Placebo-0.057
Olo 5 mcg qd0.011
Olo 10 mcg qd0.014

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FVC Peak (0-3h) Response After 24 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.223
Olo 5 mcg qd0.449
Olo 10 mcg qd0.429

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FVC Peak (0-3h) Response After 48 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.208
Olo 5 mcg qd0.415
Olo 10 mcg qd0.419

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FVC Peak (0-3h) Response After 6 Weeks

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.183
Olo 5 mcg qd0.451
Olo 10 mcg qd0.434

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FVC Peak (0-3h) Response At Day 1

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours aftertreatment. 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. (NCT00782509)
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 at Day 1

InterventionLiter (Mean)
Placebo0.202
Olo 5 mcg qd0.534
Olo 10 mcg qd0.535

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Trough FEV1 Response After 40 Weeks

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. (NCT00782509)
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 after 40 weeks

InterventionLiter (Mean)
Placebo-0.029
Olo 5 mcg qd0.033
Olo 10 mcg qd0.043

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Trough FEV1 Response After 32 Weeks

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. (NCT00782509)
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 after 32 weeks

InterventionLiter (Mean)
Placebo-0.029
Olo 5 mcg qd0.029
Olo 10 mcg qd-0.002

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Trough FEV1 Response After 24 Weeks

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. (NCT00782509)
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 after 24 weeks

InterventionLiter (Mean)
Placebo-0.036
Olo 5 mcg qd0.033
Olo 10 mcg qd0.022

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Trough FEV1 Response After 2 Weeks

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 a -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. (NCT00782509)
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 after 2 weeks

InterventionLiter (Mean)
Placebo0.013
Olo 5 mcg qd0.066
Olo 10 mcg qd0.078

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Trough FEV1 Response After 18 Weeks

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. (NCT00782509)
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 after 18 weeks

InterventionLiter (Mean)
Placebo-0.007
Olo 5 mcg qd0.062
Olo 10 mcg qd0.037

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Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

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. Moderate exacerbations were defined as exacerbations which 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.Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval.. (NCT00782509)
Timeframe: Baseline to end of study at 48 weeks.

Interventiondays (Mean)
Placebo (Tiotropium)NA
Placebo (Non-tiotropium)362.0
Olo 5 mcg qd (Tiotropium)NA
Olo 5 mcg qd (Non-tiotropium)NA
Olo 10 mcg qd (Tiotropium)225.0
Olo 10 mcg qd(Non-tiotropium)308.0

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Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization

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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval. (NCT00782509)
Timeframe: Baseline to end of study at 48 weeks.

Interventiondays (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

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Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

"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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank.~The measured values presented are actually the First Quartile and 95% confidence interval." (NCT00782509)
Timeframe: Baseline to end of study at 48 weeks.

Interventiondays (Mean)
Placebo (Tiotropium)306.0
Placebo (Non-tiotropium)259.0
Olo 5 mcg qd (Tiotropium)225.0
Olo 5 mcg qd (Non-tiotropium)315.0
Olo 10 mcg qd (Tiotropium)219.0
Olo 10 mcg qd(Non-tiotropium)216.0

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Peak FEV1 (0-3h) Response At Day 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. (NCT00782509)
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 at Day 1

InterventionLiter (Mean)
Placebo0.099
Olo 5 mcg qd0.267
Olo 10 mcg qd0.276

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Peak FEV1 (0-3h) Response After 6 Weeks

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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.080
Olo 5 mcg qd0.252
Olo 10 mcg qd0.246

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Number of COPD Exacerbations

Mean number of COPD exacerbations per patient years. 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. (NCT00782509)
Timeframe: Baseline to end of study at week 48 visit

InterventionCOPD exacerbations (Mean)
Placebo0.4590
Olo 5 mcg qd0.5453
Olo 10 mcg qd0.5885

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Number of COPD Exacerbations Requiring Hospitalization

Mean number of COPD exacerbations requiring hospitalization per patient years. 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. (NCT00782509)
Timeframe: Baseline to end of study at week 48 visit

InterventionCOPD exacerbations (Mean)
Placebo0.0786
Olo 5 mcg qd0.0811
Olo 10 mcg qd0.0886

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Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Mean number of moderate COPD exacerbations per patient years. 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. Moderate exacerbations were defined as exacerbations which did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. (NCT00782509)
Timeframe: Baseline to end of study at 48 weeks.

InterventionCOPD exacerbations (Mean)
Placebo0.3375
Olo 5 mcg qd0.4335
Olo 10 mcg qd0.4513

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Patient's Global Rating at Week 12

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782509)
Timeframe: Week 12 visit

InterventionPoint on scale (Mean)
Placebo3.2
Olo 5 mcg qd2.9
Olo 10 mcg qd3.0

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Patient's Global Rating at Week 48

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782509)
Timeframe: Week 48 visit

InterventionPoint on scale (Mean)
Placebo3.3
Olo 5 mcg qd3.1
Olo 10 mcg qd3.0

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Peak FEV1 (0-3h) Response After 12 Weeks

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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.088
Olo 5 mcg qd0.232
Olo 10 mcg qd0.217

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Peak FEV1 (0-3h) Response After 2 Weeks

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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.104
Olo 5 mcg qd0.259
Olo 10 mcg qd0.251

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Trough FVC Response After 48 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 48 weeks

InterventionLiter (Mean)
Placebo-0.008
Olo 5 mcg qd0.038
Olo 10 mcg qd0.054

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Patient's Global Rating at Week 24

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst. (NCT00782509)
Timeframe: Week 24 visit

InterventionPoint on scale (Mean)
Placebo3.3
Olo 5 mcg qd3.0
Olo 10 mcg qd2.9

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Trough FVC Response After 18 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 18 weeks

InterventionLiter (Mean)
Placebo0.064
Olo 5 mcg qd0.114
Olo 10 mcg qd0.098

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Trough FVC Response After 2 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 2 weeks

InterventionLiter (Mean)
Placebo0.054
Olo 5 mcg qd0.113
Olo 10 mcg qd0.141

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Trough FVC Response After 24 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 24 weeks

InterventionLiter (Mean)
Placebo0.021
Olo 5 mcg qd0.066
Olo 10 mcg qd0.091

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Trough FVC Response After 32 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 32 weeks

InterventionLiter (Mean)
Placebo0.061
Olo 5 mcg qd0.099
Olo 10 mcg qd0.058

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Trough FVC Response After 40 Weeks

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 FVCs obtained 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. (NCT00782509)
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 after 40 weeks

InterventionLiter (Mean)
Placebo0.062
Olo 5 mcg qd0.104
Olo 10 mcg qd0.131

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Peak FEV1 (0-3h) Response After 24 Weeks

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. (NCT00782509)
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

InterventionLiter (Mean)
Placebo0.062
Olo 5 mcg qd0.226
Olo 10 mcg qd0.197

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.023
Olo 5 mcg qd0.122
Olo 10 mcg qd0.123
Form 12 mcg0.149

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.009
Olo 5 mcg qd0.142
Olo 10 mcg qd0.156
Form 12 mcg0.168

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.015
Olo 5 mcg qd0.201
Olo 10 mcg qd0.181
Form 12 mcg0.221

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.003
Olo 5 mcg qd0.176
Olo 10 mcg qd0.167
Form 12 mcg0.182

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Absolute Plasma Concentrations

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

Interventionpg/mL (Geometric Mean)
Olo 5 mcg qd4.179
Olo 10 mcg qd7.246

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Use of Rescue Medication at Week 24

Mean number of puffs of rescue medication used per day (daytime/nighttime/total) (NCT00793624)
Timeframe: Week 24

,,,
InterventionNumber of puffs (Mean)
DaytimeNighttimeTotal
Form 12 mcg1.2171.7012.917
Olo 10 mcg qd1.0371.4712.488
Olo 5 mcg qd0.9611.4492.399
Placebo1.3642.0513.390

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Peak Expiratory Flow Rate (PEFR) at Week 24

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

,,,
InterventionL/min (Mean)
morning PEFR (N=214, 212, 216, 218)evening PEFR (N=215, 211, 215, 221)
Form 12 mcg214.070220.129
Olo 10 mcg qd211.428220.727
Olo 5 mcg qd211.496219.977
Placebo196.429202.256

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Trough FVC Response at Week 6

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.

InterventionLiter (Least Squares Mean)
Placebo-0.046
Olo 5 mcg qd0.065
Olo 10 mcg qd0.085
Form 12 mcg0.090

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Trough FVC Response at Week 48

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.

InterventionLiter (Least Squares Mean)
Placebo-0.061
Olo 5 mcg qd0.022
Olo 10 mcg qd-0.002
Form 12 mcg0.006

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Trough FVC Response at Week 40

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.

InterventionLiter (Least Squares Mean)
Placebo0.028
Olo 5 mcg qd0.087
Olo 10 mcg qd0.086
Form 12 mcg0.052

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Trough FVC Response at Week 32

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.

InterventionLiter (Least Squares Mean)
Placebo0.019
Olo 5 mcg qd0.080
Olo 10 mcg qd0.084
Form 12 mcg0.077

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Trough FVC Response at Week 24

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.

InterventionLiter (Least Squares Mean)
Placebo-0.018
Olo 5 mcg qd0.038
Olo 10 mcg qd0.064
Form 12 mcg0.001

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Trough FVC Response at Week 2

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.

InterventionLiter (Least Squares Mean)
Placebo0.042
Olo 5 mcg qd0.110
Olo 10 mcg qd0.119
Form 12 mcg0.126

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Trough FVC Response at Week 18

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.

InterventionLiter (Least Squares Mean)
Placebo0.060
Olo 5 mcg qd0.066
Olo 10 mcg qd0.078
Form 12 mcg0.063

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Trough FVC Response at Week 12

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.

InterventionLiter (Least Squares Mean)
Placebo-0.018
Olo 5 mcg qd0.079
Olo 10 mcg qd0.087
Form 12 mcg0.068

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Trough FEV1 Response at Week 6

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.

InterventionLiter (Least Squares Mean)
Placebo-0.037
Olo 5 mcg qd0.049
Olo 10 mcg qd0.041
Form 12 mcg0.042

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Trough FEV1 Response at Week 48

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.

InterventionLiter (Least Squares Mean)
Placebo-0.065
Olo 5 mcg qd0.003
Olo 10 mcg qd-0.009
Form 12 mcg-0.006

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Trough FEV1 Response at Week 40

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.

InterventionLiter (Least Squares Mean)
Placebo-0.020
Olo 5 mcg qd0.020
Olo 10 mcg qd0.017
Form 12 mcg0.004

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Trough FEV1 Response at Week 32

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.

InterventionLiter (Least Squares Mean)
Placebo-0.023
Olo 5 mcg qd0.023
Olo 10 mcg qd0.026
Form 12 mcg0.021

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Trough FEV1 Response at Week 24

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.

InterventionLiter (Least Squares Mean)
Placebo-0.056
Olo 5 mcg qd0.021
Olo 10 mcg qd0.028
Form 12 mcg-0.002

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Trough FEV1 Response at Week 2

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.

InterventionLiter (Least Squares Mean)
Placebo-0.019
Olo 5 mcg qd0.068
Olo 10 mcg qd0.060
Form 12 mcg0.061

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Trough FEV1 Response at Week 18

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.

InterventionLiter (Least Squares Mean)
Placebo-0.019
Olo 5 mcg qd0.046
Olo 10 mcg qd0.026
Form 12 mcg0.023

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Trough FEV1 Response at Week 12

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.

InterventionLiter (Least Squares Mean)
Placebo-0.027
Olo 5 mcg qd0.056
Olo 10 mcg qd0.048
Form 12 mcg0.033

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Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation

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.

InterventionDays (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

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Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization

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.

InterventionDays (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

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Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

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.

InterventionDays (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

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo40.415
Olo 5 mcg qd38.545
Olo 10 mcg qd36.850
Form 12 mcg40.431

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis

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

Interventionscore on a scale (Mean)
Placebo41.639
Olo 5 mcg qd38.794
Olo 10 mcg qd38.205
Form 12 mcg40.391

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo41.068
Olo 5 mcg qd38.627
Olo 10 mcg qd37.674
Form 12 mcg40.116

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo42.105
Olo 5 mcg qd39.320
Olo 10 mcg qd36.961
Form 12 mcg40.351

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Peak FVC (0-3h) Response After 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.202
Olo 5 mcg qd0.411
Olo 10 mcg qd0.433
Form 12 mcg0.467

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Peak FEV1 (0-3h) Response After 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.068
Olo 5 mcg qd0.216
Olo 10 mcg qd0.225
Form 12 mcg0.236

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Peak FEV1 (0-3h) Response After 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.100
Olo 5 mcg qd0.277
Olo 10 mcg qd0.250
Form 12 mcg0.290

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Peak FEV1 (0-3h) Response After 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.082
Olo 5 mcg qd0.247
Olo 10 mcg qd0.241
Form 12 mcg0.256

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Patient's Global Rating (PGR) at 6 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.4
Olo 5 mcg qd3.0
Olo 10 mcg qd3.1
Form 12 mcg3.1

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Patient's Global Rating (PGR) at 48 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.1
Olo 5 mcg qd3.0
Olo 10 mcg qd2.9
Form 12 mcg2.9

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Patient's Global Rating (PGR) at 24 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.1
Olo 5 mcg qd2.9
Olo 10 mcg qd2.9
Form 12 mcg3.0

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Patient's Global Rating (PGR) at 12 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.3
Olo 5 mcg qd3.0
Olo 10 mcg qd2.9
Form 12 mcg3.0

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Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations

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.

InterventionNumber of COPD ex. per patient year (Mean)
Placebo0.4765
Olo 5 mcg qd0.5537
Olo 10 mcg qd0.5114
Form 12 mcg0.3721

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Number of COPD Exacerbations Requiring Hospitalization

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

InterventionNumber of COPD ex. per patient year (Mean)
Placebo0.0554
Olo 5 mcg qd0.1043
Olo 10 mcg qd0.1324
Form 12 mcg0.0570

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Number of COPD Exacerbations

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

InterventionNumber of COPD ex. per patient year (Mean)
Placebo0.5684
Olo 5 mcg qd0.7117
Olo 10 mcg qd0.6946
Form 12 mcg0.5098

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Mahler Transitional Dyspnea Index Focal Score at 6 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo0.995
Olo 5 mcg qd1.566
Olo 10 mcg qd1.660
Form 12 mcg1.753

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Mahler Transitional Dyspnea Index Focal Score at 48 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.940
Olo 5 mcg qd2.035
Olo 10 mcg qd2.324
Form 12 mcg2.047

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Mahler Transitional Dyspnea Index Focal Score at 40 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.952
Olo 5 mcg qd1.839
Olo 10 mcg qd1.887
Form 12 mcg1.575

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Mahler Transitional Dyspnea Index Focal Score at 32 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.732
Olo 5 mcg qd1.898
Olo 10 mcg qd1.698
Form 12 mcg1.966

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Peak FVC (0-3h) Response After 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.193
Olo 5 mcg qd0.344
Olo 10 mcg qd0.371
Form 12 mcg0.416

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Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis

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

Interventionscore on a scale (Mean)
Placebo1.471
Olo 5 mcg qd1.980
Olo 10 mcg qd1.996
Form 12 mcg1.827

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Mahler Transitional Dyspnea Index Focal Score at 24 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo2.046
Olo 5 mcg qd2.234
Olo 10 mcg qd2.068
Form 12 mcg1.818

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Mahler Transitional Dyspnea Index Focal Score at 18 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.665
Olo 5 mcg qd1.897
Olo 10 mcg qd2.099
Form 12 mcg1.689

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.076
Olo 5 mcg qd0.299
Olo 10 mcg qd0.311
Form 12 mcg0.383

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Mahler Transitional Dyspnea Index Focal Score at 12 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.412
Olo 5 mcg qd1.792
Olo 10 mcg qd1.955
Form 12 mcg1.805

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.016
Olo 5 mcg qd0.252
Olo 10 mcg qd0.265
Form 12 mcg0.326

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.016
Olo 5 mcg qd0.196
Olo 10 mcg qd0.219
Form 12 mcg0.260

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Peak FVC (0-3h) Response After 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.207
Olo 5 mcg qd0.379
Olo 10 mcg qd0.414
Form 12 mcg0.424

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Peak FVC (0-3h) Response After 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.268
Olo 5 mcg qd0.454
Olo 10 mcg qd0.474
Form 12 mcg0.551

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Peak FVC (0-3h) Response After 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.194
Olo 5 mcg qd0.382
Olo 10 mcg qd0.432
Form 12 mcg0.450

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Peak FEV1 (0-3h) Response After 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.081
Olo 5 mcg qd0.248
Olo 10 mcg qd0.234
Form 12 mcg0.264

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Peak FEV1 (0-3h) Response After 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.053
Olo 5 mcg qd0.192
Olo 10 mcg qd0.193
Form 12 mcg0.215

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.001
Olo 5 mcg qd0.178
Olo 10 mcg qd0.161
Form 12 mcg0.194

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.023
Olo 5 mcg qd0.233
Olo 10 mcg qd0.278
Form 12 mcg0.300

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.037
Olo 5 mcg qd0.220
Olo 10 mcg qd0.252
Form 12 mcg0.279

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.021
Olo 5 mcg qd0.181
Olo 10 mcg qd0.214
Form 12 mcg0.183

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.013
Olo 5 mcg qd0.116
Olo 10 mcg qd0.140
Form 12 mcg0.137

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.025
Olo 5 mcg qd0.093
Olo 10 mcg qd0.116
Form 12 mcg0.104

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.010
Olo 5 mcg qd0.162
Olo 10 mcg qd0.181
Form 12 mcg0.174

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.006
Olo 5 mcg qd0.235
Olo 10 mcg qd0.253
Form 12 mcg0.280

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.012
Olo 5 mcg qd0.212
Olo 10 mcg qd0.225
Form 12 mcg0.253

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.036
Olo 5 mcg qd0.182
Olo 10 mcg qd0.201
Form 12 mcg0.184

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.027
Olo 5 mcg qd0.277
Olo 10 mcg qd0.276
Form 12 mcg0.307

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Mahler Transitional Dyspnea Index Focal Score at 12 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.080
Olo 5 mcg qd1.742
Olo 10 mcg qd1.747
Form 12 mcg1.499

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Mahler Transitional Dyspnea Index Focal Score at 18 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.0454
Olo 5 mcg qd1.470
Olo 10 mcg qd1.537
Form 12 mcg1.579

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Mahler Transitional Dyspnea Index Focal Score at 24 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.102
Olo 5 mcg qd1.504
Olo 10 mcg qd1.521
Form 12 mcg1.703

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Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis

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

Interventionscore on a scale (Mean)
Placebo1.471
Olo 5 mcg qd1.980
Olo 10 mcg qd1.996
Form 12 mcg1.827

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Mahler Transitional Dyspnea Index Focal Score at 32 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.168
Olo 5 mcg qd1.658
Olo 10 mcg qd1.522
Form 12 mcg1.477

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Mahler Transitional Dyspnea Index Focal Score at 40 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.064
Olo 5 mcg qd1.377
Olo 10 mcg qd1.545
Form 12 mcg1.178

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Mahler Transitional Dyspnea Index Focal Score at 48 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo1.113
Olo 5 mcg qd1.510
Olo 10 mcg qd1.831
Form 12 mcg1.280

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Mahler Transitional Dyspnea Index Focal Score at 6 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo0.980
Olo 5 mcg qd1.417
Olo 10 mcg qd1.686
Form 12 mcg1.444

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Number of COPD Exacerbations

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

InterventionNumber of COPD ex. per patient year (Mean)
Placebo0.6890
Olo 5 mcg qd0.5409
Olo 10 mcg qd0.5947
Form 12 mcg0.7325

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Number of COPD Exacerbations Requiring Hospitalization

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

InterventionNumber of COPD ex. per patient year (Mean)
Placebo0.0986
Olo 5 mcg qd0.0781
Olo 10 mcg qd0.0993
Form 12 mcg0.1025

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Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations

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.

InterventionNumber of COPD ex. per patient year (Mean)
Placebo0.5548
Olo 5 mcg qd0.4128
Olo 10 mcg qd0.4351
Form 12 mcg0.5415

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Patient's Global Rating (PGR) at 12 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.3
Olo 5 mcg qd3.1
Olo 10 mcg qd3.0
Form 12 mcg3.0

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Patient's Global Rating (PGR) at 24 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.3
Olo 5 mcg qd3.1
Olo 10 mcg qd3.1
Form 12 mcg3.1

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Patient's Global Rating (PGR) at 48 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.2
Olo 5 mcg qd3.2
Olo 10 mcg qd3.0
Form 12 mcg3.2

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Patient's Global Rating (PGR) at 6 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo3.4
Olo 5 mcg qd3.1
Olo 10 mcg qd3.2
Form 12 mcg3.1

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Peak FEV1 (0-3h) Response After 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.064
Olo 5 mcg qd0.206
Olo 10 mcg qd0.232
Form 12 mcg0.228

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Peak FEV1 (0-3h) Response After 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.099
Olo 5 mcg qd0.260
Olo 10 mcg qd0.278
Form 12 mcg0.253

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Peak FEV1 (0-3h) Response After 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.060
Olo 5 mcg qd0.183
Olo 10 mcg qd0.211
Form 12 mcg0.203

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Peak FEV1 (0-3h) Response After 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.052
Olo 5 mcg qd0.163
Olo 10 mcg qd0.178
Form 12 mcg0.170

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Peak FEV1 (0-3h) Response After 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.066
Olo 5 mcg qd0.235
Olo 10 mcg qd0.248
Form 12 mcg0.242

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Peak FVC (0-3h) Response After 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.171
Olo 5 mcg qd0.386
Olo 10 mcg qd0.396
Form 12 mcg0.436

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Peak FVC (0-3h) Response After 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.247
Olo 5 mcg qd0.480
Olo 10 mcg qd0.476
Form 12 mcg0.495

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Peak FVC (0-3h) Response After 24 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.189
Olo 5 mcg qd0.371
Olo 10 mcg qd0.369
Form 12 mcg0.397

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Peak FVC (0-3h) Response After 48 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.137
Olo 5 mcg qd0.325
Olo 10 mcg qd0.352
Form 12 mcg0.329

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Peak FVC (0-3h) Response After 6 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.196
Olo 5 mcg qd0.443
Olo 10 mcg qd0.417
Form 12 mcg0.450

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo42.679
Olo 5 mcg qd40.054
Olo 10 mcg qd40.190
Form 12 mcg39.521

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis

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

Interventionscore on a scale (Least Squares Mean)
Placebo41.639
Olo 5 mcg qd38.794
Olo 10 mcg qd38.205
Form 12 mcg40.391

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo39.914
Olo 5 mcg qd39.562
Olo 10 mcg qd38.824
Form 12 mcg40.025

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Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

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.

InterventionDays (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

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Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization

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.

InterventionDays (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

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Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation

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.

InterventionDays (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

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Trough FEV1 Response at Week 18

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.

InterventionLiter (Least Squares Mean)
Placebo-0.036
Olo 5 mcg qd0.013
Olo 10 mcg qd0.049
Form 12 mcg0.015

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Trough FEV1 Response at Week 2

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.

InterventionLiter (Least Squares Mean)
Placebo-0.016
Olo 5 mcg qd0.053
Olo 10 mcg qd0.103
Form 12 mcg0.033

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Trough FEV1 Response at Week 24

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.

InterventionLiter (Least Squares Mean)
Placebo-0.055
Olo 5 mcg qd-0.003
Olo 10 mcg qd0.014
Form 12 mcg-0.013

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Trough FEV1 Response at Week 32

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.

InterventionLiter (Least Squares Mean)
Placebo-0.039
Olo 5 mcg qd0.023
Olo 10 mcg qd0.034
Form 12 mcg0.009

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Trough FEV1 Response at Week 40

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.

InterventionLiter (Least Squares Mean)
Placebo-0.043
Olo 5 mcg qd0.019
Olo 10 mcg qd0.041
Form 12 mcg0.013

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Trough FEV1 Response at Week 48

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.

InterventionLiter (Least Squares Mean)
Placebo-0.060
Olo 5 mcg qd-0.016
Olo 10 mcg qd-0.001
Form 12 mcg-0.024

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Trough FEV1 Response at Week 6

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.

InterventionLiter (Least Squares Mean)
Placebo-0.036
Olo 5 mcg qd0.047
Olo 10 mcg qd0.068
Form 12 mcg0.034

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Trough FVC Response at Week 18

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.

InterventionLiter (Least Squares Mean)
Placebo-0.014
Olo 5 mcg qd0.084
Olo 10 mcg qd0.107
Form 12 mcg0.064

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Trough FVC Response at Week 2

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.

InterventionLiter (Least Squares Mean)
Placebo0.030
Olo 5 mcg qd0.118
Olo 10 mcg qd0.173
Form 12 mcg0.111

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Trough FVC Response at Week 24

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.

InterventionLiter (Least Squares Mean)
Placebo-0.044
Olo 5 mcg qd0.023
Olo 10 mcg qd0.019
Form 12 mcg-0.005

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Trough FVC Response at Week 32

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.

InterventionLiter (Least Squares Mean)
Placebo-0.007
Olo 5 mcg qd0.081
Olo 10 mcg qd0.063
Form 12 mcg0.036

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Trough FVC Response at Week 40

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.

InterventionLiter (Least Squares Mean)
Placebo-0.016
Olo 5 mcg qd0.071
Olo 10 mcg qd0.105
Form 12 mcg0.037

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Trough FVC Response at Week 48

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.

InterventionLiter (Least Squares Mean)
Placebo-0.069
Olo 5 mcg qd0.012
Olo 10 mcg qd0.032
Form 12 mcg-0.031

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Trough FVC Response at Week 6

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.

InterventionLiter (Least Squares Mean)
Placebo-0.014
Olo 5 mcg qd0.113
Olo 10 mcg qd0.101
Form 12 mcg0.085

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Peak Expiratory Flow Rate (PEFR) at Week 24

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

,,,
InterventionL/min (Mean)
morning PEFR (N=225, 227, 226, 224)evening PEFR (N=224, 223, 227, 222)
Form 12 mcg211.038218.321
Olo 10 mcg qd217.660225.380
Olo 5 mcg qd210.496219.905
Placebo196.789202.505

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Use of Rescue Medication at Week 24

Mean number of puffs of rescue medication used per day (daytime/nighttime/total) (NCT00796653)
Timeframe: Week 24

,,,
InterventionNumber of puffs (Mean)
DaytimeNighttimeTotal
Form 12 mcg0.9671.3932.353
Olo 10 mcg qd0.9231.3482.277
Olo 5 mcg qd1.0361.4352.470
Placebo1.1891.7132.893

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Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks

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

Interventionscore on a scale (Least Squares Mean)
Placebo42.120
Olo 5 mcg qd38.970
Olo 10 mcg qd38.597
Form 12 mcg40.704

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Trough FVC Response at Week 12

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.

InterventionLiter (Least Squares Mean)
Placebo-0.041
Olo 5 mcg qd0.062
Olo 10 mcg qd0.062
Form 12 mcg0.070

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Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo0.082
Olo 5 mcg qd0.312
Olo 10 mcg qd0.332
Form 12 mcg0.348

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Absolute Plasma Concentrations

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

Interventionpg/mL (Geometric Mean)
Olo 5 mcg qd3.920
Olo 10 mcg qd6.977

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Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks

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

InterventionLiter (Least Squares Mean)
Placebo-0.008
Olo 5 mcg qd0.138
Olo 10 mcg qd0.167
Form 12 mcg0.163

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Trough FEV1 Response at Week 12

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.

InterventionLiter (Least Squares Mean)
Placebo-0.041
Olo 5 mcg qd0.018
Olo 10 mcg qd0.052
Form 12 mcg0.024

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FEV1 Peak(0-3) Response at 4 Weeks

The change from baseline in FEV1 peak(0-3) after 4 weeks of treatment. (NCT00824382)
Timeframe: baseline and after 4 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo0.025
Olodaterol 2mcg0.170
Olodaterol 5mcg0.227
Olodaterol 10mcg0.220

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Trough FVC Response at Week 4

The change from baseline in Trough FVC after 4 weeks of treatment (NCT00824382)
Timeframe: baseline and after 4 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo-0.037
Olodaterol 2mcg0.154
Olodaterol 5mcg0.154
Olodaterol 10mcg0.150

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Weekly Mean Evening PEFR After 4 Weeks

"PEFR measurements were recorded by means of a patient diary on a daily basis. This diary was used to record the twice daily PEFs,~Evening measurements were performed at bedtime.The highest of three readings for each measurement were recorded." (NCT00824382)
Timeframe: Week 4

InterventionLiter/minute (Least Squares Mean)
Placebo227.39
Olodaterol 2mcg256.44
Olodaterol 5mcg258.34
Olodaterol 10mcg264.58

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AUC0-1,ss

Area under the concentration curve from 0 to 1 hour at steady state using trapezoid rule, only calculated if >1/3 of the patients have available pharmacokinetic parameters, thus not applicable for Olodaterol 2mcg group (NCT00824382)
Timeframe: visit at week 4

Interventionpg*h/mL (Geometric Mean)
Olodaterol 5mcg4.85
Olodaterol 10mcg10.8

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Difference From Baseline in Potassium

Difference from baseline in Potassium (normalized values). Normalization means that the values from different laboratories are transformed in such a way that they are directly comparable. (NCT00824382)
Timeframe: Baseline, Week 4

Interventionmmol/L (Mean)
Placebo0.0
Olodaterol 2mcg0.1
Olodaterol 5mcg-0.0
Olodaterol 10mcg0.1

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FEV1 AUC(0-3) Response at 4 Weeks

"The change from baseline in FEV1 AUC(0-3) after 4 weeks of treatment. 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 liters.~Due to normalization the unit is liters." (NCT00824382)
Timeframe: baseline and after 4 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo-0.020
Olodaterol 2mcg0.118
Olodaterol 5mcg0.177
Olodaterol 10mcg0.173

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FVC Peak(0-3) Response

The change from baseline in FVC peak(0-3) response after 4 weeks of treatment. (NCT00824382)
Timeframe: baseline and after 4 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo0.109
Olodaterol 2mcg0.362
Olodaterol 5mcg0.351
Olodaterol 10mcg0.335

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Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 0-6h (AUC 0-6h) Response After 4 Weeks

"Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect.~FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in liters." (NCT00824382)
Timeframe: baseline and after 4weeks treatment

InterventionLiter (Least Squares Mean)
Placebo-0.022
Olodaterol 2mcg0.090
Olodaterol 5mcg0.195
Olodaterol 10mcg0.195

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AUC0-1

Area under the concentration curve from 0 to 1 hour using trapezoid rule, only calculated if >1/3 of the patients have available pharmacokinetic parameters,thus not applicable for Olodaterol 2mcg group (NCT00824382)
Timeframe: after first inhalated administration

Interventionpg*h/mL (Geometric Mean)
Olodaterol 5mcg3.67
Olodaterol 10mcg6.08

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Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks

"Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect.~FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in liters." (NCT00824382)
Timeframe: Baseline and after 4weeks treatment

InterventionLiter (Least Squares Mean)
Placebo-0.005
Olodaterol 2mcg0.078
Olodaterol 5mcg0.171
Olodaterol 10mcg0.186

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FVC AUC(0-3) Response

"The change from baseline in FVC AUC(0-3) response after 4 weeks of treatment. 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 liters.~Due to normalization the unit is liters." (NCT00824382)
Timeframe: baseline and after 4 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo0.004
Olodaterol 2mcg0.257
Olodaterol 5mcg0.254
Olodaterol 10mcg0.237

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Cmax (Maximum Measured Concentration of the Analyte in Plasma)

Cmax only calculated if >1/3 of the patients have available pharmacokinetic parameters,thus not applicable for the Olodaterol 2 mcg (NCT00824382)
Timeframe: after first inhalated administration

Interventionpg/mL (Geometric Mean)
Olodaterol 5mcg4.17
Olodaterol 10mcg8.22

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Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks

Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol ) (NCT00824382)
Timeframe: Week 4

InterventionNumber of puffs (Mean)
Placebo0.778
Olodaterol 2mcg0.587
Olodaterol 5mcg0.324
Olodaterol 10mcg0.392

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Trough FEV1 Response at Week 2

Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to next test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline trough FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 prior to administration of the first dose of study medication (NCT00824382)
Timeframe: baseline and after 2 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo-0.020
Olodaterol 2mcg0.061
Olodaterol 5mcg0.120
Olodaterol 10mcg0.136

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Trough FEV1 Response at Week 4

The change from baseline in trough FEV1 after 4 weeks of treatment. Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to next test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline . Baseline trough FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 prior to administration of the first dose of study medication. (NCT00824382)
Timeframe: baseline and after 4 weeks treatment

InterventionLiter (Least Squares Mean)
Placebo-0.032
Olodaterol 2mcg0.059
Olodaterol 5mcg0.100
Olodaterol 10mcg0.100

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Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks

"PEFR measurements were recorded by means of a patient diary on a daily basis. This diary was used to record the twice daily PEFs,~Morning measurements were performed immediately upon arising before administration of trial and/or rescue medication.The highest of three readings for each measurement were recorded." (NCT00824382)
Timeframe: Week 4

InterventionLiter/minute (Least Squares Mean)
Placebo217.54
Olodaterol 2mcg244.80
Olodaterol 5mcg246.93
Olodaterol 10mcg254.22

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination

Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical examination. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations). (NCT00824382)
Timeframe: 4 weeks

,,,
Interventionpercentage of participants (Number)
Atrioventricular block second degreeBlood lactate dehydrogenase increasedBlood glucose increasedWhite blood cell count decreased
Olodaterol 10mcg1.20.01.21.2
Olodaterol 2mcg0.00.00.00.0
Olodaterol 5mcg0.01.30.00.0
Placebo0.00.00.00.0

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Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State)

Cmax,ss only calculated if >1/3 of the patients have available pharmacokinetic parameters, thus not applicable for the Olodaterol 2 mcg (NCT00824382)
Timeframe: visit at week 4

Interventionpg/mL (Geometric Mean)
Olodaterol 5mcg5.92
Olodaterol 10mcg13.1

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Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 24 Hours

Amount of analyte that is eliminated in urine at steady state from the time point 0 hours to time point 24 hours after dosing in week 3. The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters. Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range. (NCT00846768)
Timeframe: 3 weeks

Interventionng (Geometric Mean)
Olo 5 mcg qd181
Olo 10 mcg qd343

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Peak FVC (0-3h) Response After 3 Weeks

Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after the last dose after three weeks of treatment. (NCT00846768)
Timeframe: Baseline, 3 weeks

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.325
Olo 5 mcg qd0.417
Olo 5 mcg Bid0.349
Olo 10 mcg qd0.433

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Peak FEV1 (0-3h) Response After 3 Weeks

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the last dose after three weeks of treatment. (NCT00846768)
Timeframe: Baseline, 3 weeks

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.187
Olo 5 mcg qd0.249
Olo 5 mcg Bid0.230
Olo 10 mcg qd0.242

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FVC Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment

Response was defined as change from baseline. Baseline FVC AUC (12-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FVC 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. (NCT00846768)
Timeframe: Day 0: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to planned evening dose on day 1; Day 21: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to evening dose

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.239
Olo 5 mcg qd0.215
Olo 5 mcg Bid0.318
Olo 10 mcg qd0.219

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FVC Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment

Response was defined as change from baseline. Baseline FVC AUC (0-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FVC 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. (NCT00846768)
Timeframe: Day0:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to planned morning dose on day1, 0:30,1,2,10,11,11:50h relative to planned evening dose on day1; Day21:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to morning dose,0:30,1,2,10,11,11:50h relative to evening dose

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.249
Olo 5 mcg qd0.275
Olo 5 mcg Bid0.306
Olo 10 mcg qd0.279

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Pharmacokinetics (PK): Concentration of the Analyte in Plasma Measured at 0.167 Hours Post Dosing at Steady State

Steady state concentration of the analyte in plasma measured at 0.167 hours post dosing in week 3. The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters. Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range. (NCT00846768)
Timeframe: 3 weeks

Interventionpg/mL (Geometric Mean)
Olo 5 mcg qd3.52
Olo 5 mcg Bid4.28
Olo 10 mcg qd5.78

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FVC Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment

Response was defined as change from baseline. Baseline FVC AUC (0-12) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. FVC 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. (NCT00846768)
Timeframe: Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.262
Olo 5 mcg qd0.335
Olo 5 mcg Bid0.294
Olo 10 mcg qd0.340

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FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response After 3 Weeks of Treatment

Response was defined as change from baseline. Baseline FEV1 AUC (12-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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. (NCT00846768)
Timeframe: Day 0: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to planned evening dose on day 1; Day 21: -0:10, 0:30, 1, 2, 10, 11, 11:50 h relative to evening dose

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.167
Olo 5 mcg qd0.155
Olo 5 mcg Bid0.201
Olo 10 mcg qd0.149

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FEV1 Area Under Curve 0-24 h (AUC 0-24h) Response After 3 Weeks of Treatment

Response was defined as change from baseline. Baseline FEV1 AUC (0-24) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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. (NCT00846768)
Timeframe: Day0:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to planned morning dose on day1,0:30,1,2,10,11,11:50h relative to planned evening dose on day1; Day21:-0:10,0:30,1,2,3,4,6,8,10,11:50h relative to morning dose,0:30,1,2,10,11,11:50h relative to evening dose

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.160
Olo 5 mcg qd0.182
Olo 5 mcg Bid0.195
Olo 10 mcg qd0.176

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FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After 3 Weeks of Treatment

Response was defined as change from baseline. Baseline FEV1 AUC (0-12) was defined as the AUC performed on the baseline visit, prior to the first dose of randomized treatment. 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. (NCT00846768)
Timeframe: Day 0: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to planned morning dose on day 1; Day 21: -0:10, 0:30, 1, 2, 3, 4, 6, 8, 10, 11:50 h relative to morning dose

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.155
Olo 5 mcg qd0.209
Olo 5 mcg Bid0.189
Olo 10 mcg qd0.204

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Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 24 Hours

Fraction of analyte eliminated in urine at steady state from time point 0 hours to time point 24 hours after dosing in week 3. The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters. Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range. (NCT00846768)
Timeframe: 3 weeks

Interventionpercent (Geometric Mean)
Olo 5 mcg qd3.61
Olo 10 mcg qd3.43

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Trough FEV1 Response

Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values prior to first dose of treatment. Trough values were the mean of values obtained 23h and 23 h 50 min after the last dose of study drug after three weeks of treatment . (NCT00846768)
Timeframe: Baseline, 3 weeks

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.093
Olo 5 mcg qd0.108
Olo 5 mcg Bid0.129
Olo 10 mcg qd0.087

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Pharmacokinetics (PK): Fraction of Analyte Eliminated in Urine at Steady State From Time Point 0 Hours to Time Point 12 Hours

"Fraction of analyte eliminated in urine at steady state from time point 0 hours to time point 12 hours after dosing in week 3 (after the morning dose for the bid dose regimens). The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters.~Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range." (NCT00846768)
Timeframe: 3 weeks

Interventionpercent (Geometric Mean)
Olo 2 mcg Bid3.41
Olo 5 mcg qd2.29
Olo 5 mcg Bid3.55
Olo 10 mcg qd2.13

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination

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). (NCT00846768)
Timeframe: 3 weeks

,,,
Interventionpercentage of participants (Number)
Cardiac disordersInvestigations
Olo 10 mcg qd0.00.0
Olo 2 mcg Bid0.00.0
Olo 5 mcg Bid0.00.0
Olo 5 mcg qd0.00.0

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Pharmacokinetics (PK): Amount of Analyte That is Eliminated in Urine at Steady State From the Time Point 0 Hours to Time Point 12 Hours

"Amount of analyte that is eliminated in urine at steady state from the time point 0 hours to time point 12 hours after dosing in week 3 (after the morning dose for the bid dose regimens). The start of inhalation was used as time point 0 for calculation of pharmacokinetic parameters.~Descriptive statistics were calculated only if N>=16 had concentrations within the validated concentration range." (NCT00846768)
Timeframe: 3 weeks

Interventionng (Geometric Mean)
Olo 2 mcg Bid68.2
Olo 5 mcg qd115
Olo 5 mcg Bid177
Olo 10 mcg qd213

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Trough FVC Response

Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values prior to first dose of treatment. Trough values were the mean of values obtained 23h and 23 h 50 min after the last dose of study drug after three weeks of treatment . (NCT00846768)
Timeframe: Baseline, 3 weeks

InterventionLiter (Least Squares Mean)
Olo 2 mcg Bid0.111
Olo 5 mcg qd0.177
Olo 5 mcg Bid0.181
Olo 10 mcg qd0.162

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Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 30 Minutes

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 30 minutes (NCT00928668)
Timeframe: 30 minutes post dose

InterventionLog base 2 (mg/ml) (Least Squares Mean)
Placebo0.393
Olodaterol (Olo) 2 mcg qd2.532
Olodaterol (Olo) 5 mcg qd3.029
Olodaterol (Olo) 10 mcg qd3.953
Olodaterol (Olo) 20 mcg qd4.617

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Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 24 Hours

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 24 hours (NCT00928668)
Timeframe: 24 hours post dose

InterventionLog base 2 (mg/ml) (Least Squares Mean)
Placebo0.793
Olodaterol (Olo) 2 mcg qd1.950
Olodaterol (Olo) 5 mcg qd2.504
Olodaterol (Olo) 10 mcg qd3.236
Olodaterol (Olo) 20 mcg qd3.777

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Laboratory Testing: Average Change From Baseline of Potassium and Calcium

Laboratory testing: Average change from baseline of potassium and calcium measured on test-days (NCT00928668)
Timeframe: Baseline to Visit 6

,,,,
Interventionmmol/L (Geometric Mean)
PotassiumCalcium
Olodaterol (Olo) 10 mcg qd1.001.00
Olodaterol (Olo) 2 mcg qd1.041.01
Olodaterol (Olo) 20 mcg qd0.981.01
Olodaterol (Olo) 5 mcg qd1.021.00
Placebo1.011.00

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

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 (cardiac disorders and investigations). (NCT00928668)
Timeframe: 5 days

,,,,
Interventionpercentage of participants (Number)
Cardiac disordersInvestigations
Olo 10 mcg00
Olo 2 mcg00
Olo 20 mcg00
Olo 5 mcg00
Placebo00

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Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 8 Hours

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 8 hours (NCT00928668)
Timeframe: 8 hours post dose

InterventionLog base 2 (mg/ml) (Least Squares Mean)
Placebo0.576
Olodaterol (Olo) 2 mcg qd2.484
Olodaterol (Olo) 5 mcg qd3.050
Olodaterol (Olo) 10 mcg qd3.903
Olodaterol (Olo) 20 mcg qd4.796

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Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 4 Hours

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 4 hours (NCT00928668)
Timeframe: 4 hours post dose

InterventionLog base 2 (mg/ml) (Least Squares Mean)
Placebo0.577
Olodaterol (Olo) 2 mcg qd2.602
Olodaterol (Olo) 5 mcg qd2.957
Olodaterol (Olo) 10 mcg qd4.126
Olodaterol (Olo) 20 mcg qd4.786

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Adjusted Mean of Provocative Concentration of Methacholine Required to Produce a 20% Decrease in FEV1 (PC20FEV1) at 32 Hours

Provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20FEV1) at 32 hours (NCT00928668)
Timeframe: 32 hours post dose

InterventionLog base 2 (mg/ml) (Least Squares Mean)
Placebo0.960
Olodaterol (Olo) 2 mcg qd2.189
Olodaterol (Olo) 5 mcg qd2.785
Olodaterol (Olo) 10 mcg qd3.074
Olodaterol (Olo) 20 mcg qd3.605

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

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

,,,
Interventionparticipants (Number)
Bundle branch block rightECG QT prolongedTachycardia
Form 12 mcg001
Olo 10 mcg110
Olo 5 mcg000
Placebo000

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Trough FVC Response

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

InterventionLiter (Least Squares Mean)
Placebo-0.007
Olo 5 mcg qd0.125
Olo 10 mcg qd0.133
Form 12 mcg Bid0.141

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Trough FEV1 Response

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

InterventionLiter (Least Squares Mean)
Placebo0.012
Olo 5 mcg qd0.109
Olo 10 mcg qd0.115
Form 12 mcg Bid0.093

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Peak FVC (0-3h) Response

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

InterventionLiter (Least Squares Mean)
Placebo0.138
Olo 5 mcg qd0.436
Olo 10 mcg qd0.440
Form 12 mcg Bid0.475

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FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

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

InterventionLiter (Least Squares Mean)
Placebo-0.078
Olo 5 mcg qd0.083
Olo 10 mcg qd0.079
Form 12 mcg Bid0.144

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FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

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.

InterventionLiter (Least Squares Mean)
Placebo-0.055
Olo 5 mcg qd0.151
Olo 10 mcg qd0.147
Form 12 mcg Bid0.174

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Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

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

InterventionLiter (Least Squares Mean)
Placebo-0.032
Olo 5 mcg qd0.219
Olo 10 mcg qd0.214
Form 12 mcg Bid0.203

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment

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

InterventionLiter (Least Squares Mean)
Placebo0.004
Olo 5 mcg qd0.190
Olo 10 mcg qd0.202
Form 12 mcg Bid0.217

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment

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.

InterventionLiter (Least Squares Mean)
Placebo-0.035
Olo 5 mcg qd0.110
Olo 10 mcg qd0.112
Form 12 mcg Bid0.121

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Peak FEV1 (0-3h) Response

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

InterventionLiter (Least Squares Mean)
Placebo0.076
Olo 5 mcg qd0.268
Olo 10 mcg qd0.273
Form 12 mcg Bid0.293

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FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment

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

InterventionLiter (Least Squares Mean)
Placebo-0.022
Olo 5 mcg qd0.150
Olo 10 mcg qd0.152
Form 12 mcg Bid0.136

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FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment

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

InterventionLiter (Least Squares Mean)
Placebo-0.048
Olo 5 mcg qd0.069
Olo 10 mcg qd0.072
Form 12 mcg Bid0.107

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Peak FVC Within 24 Hours Post-dose Response

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

InterventionLiter (Mean)
Placebo0.253
Olo 2 mcg qd0.300
Olo 5 mcg qd0.356
Olo 10 mcg qd0.342
Olo 20 mcg qd0.380
Form 12 mcg Bid0.326

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Peak PEF Within 24 Hours Post-dose Response

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

InterventionLiter/sec (Mean)
Placebo0.664
Olo 2 mcg qd0.966
Olo 5 mcg qd1.093
Olo 10 mcg qd1.130
Olo 20 mcg qd1.198
Form 12 mcg Bid1.168

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PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response

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

InterventionLiter/sec (Mean)
Placebo0.043
Olo 2 mcg qd0.380
Olo 5 mcg qd0.528
Olo 10 mcg qd0.575
Olo 20 mcg qd0.692
Form 12 mcg Bid0.594

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PEF Daily Variability

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

InterventionPercentage (Mean)
Placebo11.688
Olo 2 mcg qd9.694
Olo 5 mcg qd9.593
Olo 10 mcg qd9.851
Olo 20 mcg qd9.899
Form 12 mcg Bid10.417

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Percentage of Asthma Symptom Free Days

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

InterventionPercentage of asthma symptom free days (Mean)
Placebo18.502
Olo 2 mcg qd26.430
Olo 5 mcg qd22.348
Olo 10 mcg qd23.624
Olo 20 mcg qd21.326
Form 12 mcg Bid23.664

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Potassium 1 Hour Post-dose

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

Interventionmmol/L (Geometric Mean)
Placebo4.097
Olo 2 mcg qd4.069
Olo 5 mcg qd4.013
Olo 10 mcg qd4.004
Olo 20 mcg qd4.015
Form 12 mcg Bid4.059

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Potassium 1 Hour Pre-dose

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

Interventionmmol/L (Geometric Mean)
Placebo4.067
Olo 2 mcg qd4.051
Olo 5 mcg qd4.051
Olo 10 mcg qd4.061
Olo 20 mcg qd4.057
Form 12 mcg Bid4.080

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Potassium 3 Hours Post-dose

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

Interventionmmol/L (Geometric Mean)
Placebo4.029
Olo 2 mcg qd4.026
Olo 5 mcg qd3.997
Olo 10 mcg qd3.979
Olo 20 mcg qd3.992
Form 12 mcg Bid4.007

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Total Asthma Control Questionnaire (ACQ) Score

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

Interventionunits on a scale (Mean)
Placebo1.882
Olo 2 mcg qd1.561
Olo 5 mcg qd1.589
Olo 10 mcg qd1.556
Olo 20 mcg qd1.488
Form 12 mcg Bid1.536

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Total Asthma Quality of Life Questionnaire (AQLQ(s)) Score

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

Interventionunits on a scale (Mean)
Placebo5.174
Olo 2 mcg qd5.463
Olo 5 mcg qd5.383
Olo 10 mcg qd5.437
Olo 20 mcg qd5.491
Form 12 mcg Bid5.489

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Trough FEV1 Response

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

InterventionLiter (Mean)
Placebo0.013
Olo 2 mcg qd0.116
Olo 5 mcg qd0.146
Olo 10 mcg qd0.182
Olo 20 mcg qd0.211
Form 12 mcg Bid0.115

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Trough FVC Response

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

InterventionLiter (Mean)
Placebo-0.022
Olo 2 mcg qd0.015
Olo 5 mcg qd0.069
Olo 10 mcg qd0.088
Olo 20 mcg qd0.107
Form 12 mcg Bid0.029

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Trough PEF Response

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

InterventionLiter/sec (Mean)
Placebo0.031
Olo 2 mcg qd0.295
Olo 5 mcg qd0.499
Olo 10 mcg qd0.515
Olo 20 mcg qd0.655
Form 12 mcg Bid0.478

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

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

,,,,,
InterventionParticipants (Number)
Atrioventricular block first degreeBlood creatine phosphokinase MB increasedBlood creatine phosphokinase increasedBlood pressure increasedHypothyroidismHypertension
Form 12 mcg Bid100000
Olo 10 mcg qd011001
Olo 2 mcg qd000100
Olo 20 mcg qd100001
Olo 5 mcg qd000011
Placebo000000

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Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)

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

,,,,,
InterventionNumber of patients (Number)
Did not wake upWoke up onceWoke up 2-5 timesWoke up > 5 timesWas awake all night
Form 12 mcg Bid59293320
Olo 10 mcg qd56343012
Olo 2 mcg qd60361751
Olo 20 mcg qd63342021
Olo 5 mcg qd58343022
Placebo55372631

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Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)

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

,,,,,
InterventionNumber of patients (Number)
No asthma symptomsMild asthma symptomsModerate asthma symptomsSevere asthma symptomsVery severe asthma symptoms
Form 12 mcg Bid243749121
Olo 10 mcg qd233752101
Olo 2 mcg qd264637100
Olo 20 mcg qd21385461
Olo 5 mcg qd292951125
Placebo203156150

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Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)

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

,,,,,
InterventionNumber of patients (Number)
No asthma symptomsMild asthma symptomsModerate asthma symptomsSevere asthma symptomsVery severe asthma symptoms
Form 12 mcg Bid263946102
Olo 10 mcg qd254046102
Olo 2 mcg qd314729102
Olo 20 mcg qd27454350
Olo 5 mcg qd224845110
Placebo273249140

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FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response at the End of Each Treatment Period

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

InterventionLiter (Mean)
Placebo-0.039
Olo 2 mcg qd0.124
Olo 5 mcg qd0.173
Olo 10 mcg qd0.194
Olo 20 mcg qd0.211
Form 12 mcg Bid0.145

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FEV1 Area Under Curve 12-24 h (AUC 12-24h) Response at the End of Each Treatment Period

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

InterventionLiter (Mean)
Placebo0.031
Olo 2 mcg qd0.147
Olo 5 mcg qd0.183
Olo 10 mcg qd0.208
Olo 20 mcg qd0.238
Form 12 mcg Bid0.183

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period

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

InterventionLiter (Mean)
Placebo-0.004
Olo 2 mcg qd0.135
Olo 5 mcg qd0.178
Olo 10 mcg qd0.201
Olo 20 mcg qd0.225
Form 12 mcg Bid0.164

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Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

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

InterventionLiter (Mean)
Placebo-0.047
Olo 2 mcg qd0.056
Olo 5 mcg qd0.109
Olo 10 mcg qd0.094
Olo 20 mcg qd0.122
Form 12 mcg Bid0.055

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FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

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

InterventionLiter (Mean)
Placebo-0.026
Olo 2 mcg qd0.056
Olo 5 mcg qd0.109
Olo 10 mcg qd0.102
Olo 20 mcg qd0.131
Form 12 mcg Bid0.070

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FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

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

InterventionLiter (Mean)
Placebo-0.005
Olo 2 mcg qd0.055
Olo 5 mcg qd0.109
Olo 10 mcg qd0.110
Olo 20 mcg qd0.139
Form 12 mcg Bid0.085

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Mean Number of Puffs of Rescue Medication During the Whole Day

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

InterventionNumber of Puffs (Mean)
Placebo1.749
Olo 2 mcg qd1.222
Olo 5 mcg qd1.317
Olo 10 mcg qd1.271
Olo 20 mcg qd1.092
Form 12 mcg Bid1.300

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Mean Pre-dose Evening FEV1 (FEV1 p.m.)

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

InterventionL (Mean)
Placebo2.378
Olo 2 mcg qd2.428
Olo 5 mcg qd2.460
Olo 10 mcg qd2.467
Olo 20 mcg qd2.495
Form 12 mcg Bid2.457

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Mean Pre-dose Evening PEF (PEF p.m.)

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

InterventionLiter/min (Mean)
Placebo379.44
Olo 2 mcg qd394.36
Olo 5 mcg qd404.28
Olo 10 mcg qd403.06
Olo 20 mcg qd407.89
Form 12 mcg Bid399.88

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Mean Pre-dose Morning FEV1 (FEV1 a.m.)

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

InterventionL (Mean)
Placebo2.309
Olo 2 mcg qd2.402
Olo 5 mcg qd2.438
Olo 10 mcg qd2.445
Olo 20 mcg qd2.479
Form 12 mcg Bid2.403

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Mean Pre-dose Morning PEF (PEF a.m.)

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

InterventionLiter/min (Mean)
Placebo361.89
Olo 2 mcg qd383.90
Olo 5 mcg qd390.91
Olo 10 mcg qd389.78
Olo 20 mcg qd394.82
Form 12 mcg Bid385.42

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Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response

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

InterventionLiter/sec (Mean)
Placebo-0.117
Olo 2 mcg qd0.291
Olo 5 mcg qd0.449
Olo 10 mcg qd0.495
Olo 20 mcg qd0.553
Form 12 mcg Bid0.471

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Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response

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

InterventionLiter/sec (Mean)
Placebo-0.038
Olo 2 mcg qd0.336
Olo 5 mcg qd0.489
Olo 10 mcg qd0.534
Olo 20 mcg qd0.623
Form 12 mcg Bid0.532

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Peak FEV1 Within 24 Hours Post-dose Response

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

InterventionLiter (Mean)
Placebo0.224
Olo 2 mcg qd0.326
Olo 5 mcg qd0.359
Olo 10 mcg qd0.385
Olo 20 mcg qd0.404
Form 12 mcg Bid0.390

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Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.473
Olo 5 mcg qd1.698
Olo 10 mcg qd1.699

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Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters/second (Least Squares Mean)
Placebo4.374
Olo 5 mcg qd4.692
Olo 10 mcg qd4.677

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Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo3.212
Olo 5 mcg qd3.319
Olo 10 mcg qd3.310

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Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo4.950
Olo 5 mcg qd4.740
Olo 10 mcg qd4.577

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Number of Patients With Notable Increase in QRS Intervals

Number of Patients with notable increase in QRS intervals. Notable QRS interval increase defined as >=10% increase and on-treatment QRS interval > 110 ms. (NCT01040130)
Timeframe: Baseline and Week 6

,,
Interventionpercentage of participants (Number)
30 min pre-dose: increase (N=138, 139, 140)30 min pre-dose: no increase (N=138, 139, 140)40 min post-dose: increase (N=138, 141, 138)40 min post-dose: no increase (N=138, 141, 138)
Olo 10 mcg0.0100.00.799.3
Olo 5 mcg0.799.30.799.3
Placebo0.799.30.799.3

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Number of Patients With Notable Increase in PR Intervals

Number of Patients with notable increase in PR intervals. Notable PR interval increase defined as >=25% increase and on-treatment PR interval > 200 ms. (NCT01040130)
Timeframe: Baseline and Week 6

,,
Interventionpercentage of participants (Number)
30 min pre-dose: increase (N=137, 137, 139)30 min pre-dose: no increase (N=137, 137, 139)40 min post-dose: increase (N=137, 140, 137)40 min post-dose: no increase (N=137, 140, 137)
Olo 10 mcg0.0100.00.799.3
Olo 5 mcg0.799.30.0100.0
Placebo0.0100.00.0100.0

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Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters/second (Least Squares Mean)
Placebo4.363
Olo 5 mcg qd4.949
Olo 10 mcg qd4.981

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Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.220
Olo 5 mcg qd2.478
Olo 10 mcg qd2.513

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Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks

Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods. (NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.917
Olo 5 mcg qd2.099
Olo 10 mcg qd2.091

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Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.887
Olo 5 mcg qd2.067
Olo 10 mcg qd2.024

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Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks

Measured using body plethysmography (NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.170
Olo 5 mcg qd2.289
Olo 10 mcg qd2.262

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Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks

Measured using body plethysmography (NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.221
Olo 5 mcg qd2.427
Olo 10 mcg qd2.437

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Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo3.187
Olo 5 mcg qd3.471
Olo 10 mcg qd3.477

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Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo4.977
Olo 5 mcg qd4.855
Olo 10 mcg qd4.862

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Number of Patients With Notable Changes in Heart Rate

Number of Patients with notable changes in heart rate (HR). Notable HR increase defined as >=25% increase and on-treatment HR > 100 bpm; Notable HR decrease defined as >=25% decrease and on-treatment HR < 50 bpm. (NCT01040130)
Timeframe: Baseline and Week 6

,,
Interventionpercentage of participants (Number)
30 min pre-dose: increase (N=138, 139, 140)30 min pre-dose: decrease (N=138, 139, 140)30 min pre-dose: no change (N=138, 139, 140)40 min post-dose: increase (N=138, 141, 138)40 min post-dose: decrease (N=138, 141, 138)40 min post-dose: no change (N=138, 141, 138)
Olo 10 mcg0.72.197.12.96.590.6
Olo 5 mcg0.72.996.41.45.093.6
Placebo0.71.497.82.24.393.5

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Change From Baseline to Day 43 in Blood Pressure

Change from Baseline to Day 43 in Blood Pressure with spirometry. Baseline is defined as mean of pre-treatment values at a given time point. (NCT01040130)
Timeframe: Baseline and Week 6

,,
InterventionmmHg (Mean)
Systolic blood pressureDiastolic blood pressure
Olo 10 mcg-3.3-1.1
Olo 5 mcg-2.7-1.8
Placebo-3.5-1.7

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Change From Baseline to Day 43 in Pulse Rate

Change from Baseline to Day 43 in Pulse rate with spirometry. Baseline is defined as mean of pre-treatment values at a given time point. (NCT01040130)
Timeframe: Baseline and Week 6

Interventionbeats/min (Mean)
Placebo-5.1
Olo 5 mcg-5.1
Olo 10 mcg-3

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Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort. (NCT01040130)
Timeframe: 6 weeks

InterventionScores on a scale (Least Squares Mean)
Placebo6.978
Olo 5 mcg qd6.890
Olo 10 mcg qd7.234

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Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks

"Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.~Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort." (NCT01040130)
Timeframe: 6 weeks

InterventionScores on a scale (Least Squares Mean)
Placebo5.870
Olo 5 mcg qd5.104
Olo 10 mcg qd5.235

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Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort. (NCT01040130)
Timeframe: 6 weeks

InterventionScores on a scale (Least Squares Mean)
Placebo0.288
Olo 5 mcg qd0.185
Olo 10 mcg qd0.224

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Adjusted Mean Endurance Time After 6 Weeks

Primary endpoint was endurance time during constant work rate ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. Mixed effects model on log10 transformation data. Adjusted means are back transformed to report as geometric means. Standard errors (SEs) are calculated using the delta method. (NCT01040130)
Timeframe: 6 weeks

Interventionseconds (Geometric Mean)
Placebo369.81
Olo 5 mcg qd421.58
Olo 10 mcg qd420.72

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Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.475
Olo 5 mcg qd1.564
Olo 10 mcg qd1.576

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Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks

Measured using body plethysmography (NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo7.142
Olo 5 mcg qd7.148
Olo 10 mcg qd7.121

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Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks

(NCT01040130)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo7.156
Olo 5 mcg qd7.142
Olo 10 mcg qd6.997

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PEF Peak 0-3h Response After the First Dose

Adjusted means of the Peak Expiratory flow from 0 to 3 hours response in L/min after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

InterventionL/min (Mean)
Olo 552.129
T+O 1.25/553.298
T+O 2.5/556.565
T+O 5/557.318
Olo 1051.980
T+O 1.25/1054.966
T+O 2.5/1056.896
T+O 5/1059.412

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PEF AUC 0-3h Response After the First Dose

Adjusted means of the Area under the curve from 0 to 3 h response in Litres / minutes of the peak expiratory flow after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

InterventionL/min (Mean)
Olo 530.575
T+O 1.25/532.891
T+O 2.5/535.053
T+O 5/535.243
Olo 1031.724
T+O 1.25/1033.213
T+O 2.5/1034.987
T+O 5/1038.846

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Patients Global Rating

"Adjusted means of the Global Rating of the patients' health (respiratory condition) on day 29.~The score was evaluated on a 7-point scale :~1 : very much better~2 : much better~3 : a little better~4 : no change~5 : a little worse~6 : much worse~7 : very much worse" (NCT01040403)
Timeframe: Day 29

Interventionunits on a scale (Mean)
Olo 53.357
T+O 1.25/53.135
T+O 2.5/52.916
T+O 5/53.208
Olo 103.262
T+O 1.25/102.880
T+O 2.5/103.130
T+O 5/102.936

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FVC Peak 0-3h Response After the First Dose

Adjusted mean of the FVC peak 0-3h response [L] after the first dose. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

InterventionLitres (Mean)
Olo 50.473
T+O 1.25/50.423
T+O 2.5/50.481
T+O 5/50.462
Olo 100.436
T+O 1.25/100.547
T+O 2.5/100.517
T+O 5/100.505

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FVC Peak 0-3h Response

Adjusted means of the FVC peak 0-3h response [L] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29

InterventionLitres (Mean)
Olo 50.415
T+O 1.25/50.570
T+O 2.5/50.563
T+O 5/50.542
Olo 100.411
T+O 1.25/100.585
T+O 2.5/100.593
T+O 5/100.615

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FVC AUC 0-3h Response After First Dose

Adjusted means of the FVC AUC 0-3h response [L] after first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on days 1

InterventionLitres (Mean)
Olo 50.333
T+O 1.25/50.285
T+O 2.5/50.326
T+O 5/50.319
Olo 100.303
T+O 1.25/100.393
T+O 2.5/100.363
T+O 5/100.359

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FEV1 Peak 0-3h Response After the First Dose

Adjusted means of the FEV1 peak 0-3h response [L] after the first dose of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

InterventionLitres (Mean)
Olo 50.287
T+O 1.25/50.267
T+O 2.5/50.300
T+O 5/50.298
Olo 100.270
T+O 1.25/100.324
T+O 2.5/100.315
T+O 5/100.317

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FEV1 Peak 0-3h Response

Adjusted means of the FEV1 peak value over the time from 0 to 3 hours (peak 0-3h) response [L] after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29

InterventionLitres (Mean)
Olo 50.264
T+O 1.25/50.353
T+O 2.5/50.355
T+O 5/50.379
Olo 100.267
T+O 1.25/100.374
T+O 2.5/100.399
T+O 5/100.412

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FEV1 AUC 0-3h Response After the First Dose

Adjusted means of Forced Expiratory Volume in One Second (FEV1) Area Under Curve (AUC) 0-3h response [L] after the first dose, calculated using the trapezoidal rule, divided by the duration (3 hours) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1

InterventionLitres (Mean)
Olo 50.204
T+O 1.25/50.181
T+O 2.5/50.209
T+O 5/50.205
Olo 100.188
T+O 1.25/100.227
T+O 2.5/100.219
T+O 5/100.230

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PEF Peak 0-3h Response

Adjusted means of the peak expiratory flow from 0 to 3 hours (PEF peak 0-3h) response in L/min after 4 weeks of treatment. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29

InterventionL/min (Mean)
Olo 546.010
T+O 1.25/564.693
T+O 2.5/569.610
T+O 5/576.108
Olo 1049.025
T+O 1.25/1066.767
T+O 2.5/1073.140
T+O 5/1074.120

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Weekly Mean Number of Puffs of Rescue Medication Used Per Day

Adjusted means of the weekly mean number of puffs of rescue medication during the whole day : the rescue medication was a salbutamol [albuterol] dose (100 mcg per puff). (NCT01040403)
Timeframe: Weeks 1 and 4

,,,,,,,
Interventionnumber of puffs per day (Mean)
Week 1Week 4
Olo 101.4231.561
Olo 51.5111.391
T+O 1.25/101.4651.344
T+O 1.25/51.2981.502
T+O 2.5/101.1721.198
T+O 2.5/51.1911.299
T+O 5/101.2441.315
T+O 5/51.4461.444

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Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry

Systolic and diastolic blood pressure recorded in conjunction with spirometry change from baseline on day 29 in millimetres of mercury (mmHg). (NCT01040403)
Timeframe: Baseline and 30 min post-dose on day 29

,,,,,,,
InterventionmmHg (Mean)
Systolic blood pressureDiastolic blood pressure
Olo 10-3.4-3.0
Olo 5-7.2-3.8
T+O 1.25/10-5.5-3.0
T+O 1.25/5-6.0-2.8
T+O 2.5/10-3.8-2.5
T+O 2.5/5-5.6-2.5
T+O 5/10-2.2-0.4
T+O 5/5-4.8-3.0

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Physicians Global Evaluation

"Adjusted means of the Physicians Global Evaluation of the patient's respiratory condition on days 1 and 29.~The score was evaluated on a 8-points scale :~Poor : 1,2~Fair : 3,4~Good : 5,6~Excellent : 7,8" (NCT01040403)
Timeframe: Days 1 and 29

,,,,,,,
Interventionunits on a scale (Mean)
Day 1Day 29
Olo 104.7475.109
Olo 54.6184.985
T+O 1.25/104.4645.280
T+O 1.25/54.6315.146
T+O 2.5/104.6345.165
T+O 2.5/54.4845.248
T+O 5/104.6905.227
T+O 5/54.5795.070

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PEF AUC 0-3h and AUC 0-6h Responses

Adjusted means of the Peak Expiratory Flow (PEF) AUC 0-3h and AUC 0-6h responses in Litres / minute (L/min) after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29

,,,,,,,
InterventionL/min (Mean)
AUC 0-3hAUC 0-6h
Olo 1029.71331.831
Olo 525.54228.071
T+O 1.25/1048.03251.485
T+O 1.25/544.30146.822
T+O 2.5/1053.22454.593
T+O 2.5/550.69854.081
T+O 5/1052.53157.367
T+O 5/555.34657.418

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Individual PEF Measurements at Each Time Point on Day 29

Adjusted means of the PEF measurements [L/min] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29

,,,,,,,
InterventionL/min (Mean)
Timepoint -1:00 hr responseTimepoint -0:10 hr responseTimepoint 0:00 hr responseTimepoint 0:05 hr responseTimepoint 0:30 hr responseTimepoint 1:00 hr responseTimepoint 2:00 hr responseTimepoint 3:00 hr responseTimepoint 4:00 hr responseTimepoint 5:00 hr responseTimepoint 6:00 hr response
Olo 10249.356253.921251.517259.301264.909263.293272.318274.334274.466269.220270.707
Olo 5246.557245.661245.758254.967257.326261.890269.187269.067266.451272.141268.680
T+O 1.25/10263.134264.808263.757271.071280.836283.326291.503295.008293.986293.039290.283
T+O 1.25/5260.901264.412262.239267.969275.045279.892287.181292.962286.382287.917284.028
T+O 2.5/10267.013268.772267.623276.004287.502288.427298.394296.641293.617294.713293.466
T+O 2.5/5263.662265.177264.202273.340279.309287.635295.820296.736297.483293.878295.843
T+O 5/10266.913266.506266.187275.727288.289288.585294.627300.582302.539300.335299.234
T+O 5/5269.754271.793270.565275.329286.288289.866300.076303.099297.415295.911295.703

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Individual FVC Measurements at Each Time Point on Day 29

Adjusted means of the FVC measurements [L] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29

,,,,,,,
InterventionLitres (Mean)
Timepoint -1:00 hr responseTimepoint -0:10 hr responseTimepoint 0:00 hr responseTimepoint 0:05 hr responseTimepoint 0:30 hr responseTimepoint 1:00 hr responseTimepoint 2:00 hr responseTimepoint 3:00 hr responseTimepoint 4:00 hr responseTimepoint 5:00 hr responseTimepoint 6:00 hr response
Olo 102.8772.9042.8893.0093.0193.0323.0713.0813.0543.0193.028
Olo 52.8772.8912.8822.9993.0183.0363.0773.0673.0543.0613.035
T+O 1.25/103.0063.0363.0203.1413.1903.2043.2583.2643.2663.2223.228
T+O 1.25/52.9613.0072.9813.1303.1713.1743.2163.2223.1813.1933.163
T+O 2.5/103.0123.0323.0203.1473.1923.2153.2493.2673.2273.2143.208
T+O 2.5/52.9963.0093.0023.1203.1453.1903.2343.2333.2043.1883.197
T+O 5/103.0073.0323.0163.1483.2193.2393.2753.3033.2813.2523.261
T+O 5/52.9543.0122.9823.0873.1723.1623.2083.2003.1833.1783.179

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Individual FEV1 Measurements at Each Time Point on Day 29

Adjusted means of the FEV1 measurements [L] at each time point on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29

,,,,,,,
InterventionLitres (Mean)
Timepoint -1:00 hr responseTimepoint -0:10 hr responseTimepoint 0:00 hr responseTimepoint 0:05 hr responseTimepoint 0:30 hr responseTimepoint 1:00 hr responseTimepoint 2:00 hr responseTimepoint 3:00 hr responseTimepoint 4:00 hr responseTimepoint 5:00 hr responseTimepoint 6:00 hr response
Olo 101.4141.4471.4311.4911.5241.5271.5561.5671.5631.5401.547
Olo 51.4101.4311.4191.4831.5161.5211.5521.5531.5431.5491.517
T+O 1.25/101.4671.4981.4821.5761.6051.6271.6611.6711.6631.6401.636
T+O 1.25/51.4641.4871.4731.5551.5701.5951.6251.6481.6211.6221.605
T+O 2.5/101.5041.5261.5141.5931.6431.6581.6991.6901.6761.6551.656
T+O 2.5/51.4811.4881.4841.5531.5971.6221.6561.6591.6541.6261.631
T+O 5/101.5001.5271.5111.6011.6601.6751.7111.7161.7081.6881.687
T+O 5/51.4911.5161.5031.5631.6301.6331.6871.6711.6591.6541.647

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FVC AUC 0-3h and FEV1 AUC 0-6h Responses

Adjusted means of the FVC AUC 0-3h and AUC 0-6h responses [L] after 4 weeks of treatment, calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29

,,,,,,,
InterventionLitres (Mean)
AUC 0-3hAUC 0-6h
Olo 100.2790.277
Olo 50.2780.282
T+O 1.25/100.4550.466
T+O 1.25/50.4220.421
T+O 2.5/100.4540.456
T+O 2.5/50.4290.432
T+O 5/100.4790.490
T+O 5/50.4100.414

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FEV1 AUC 0-3h and FEV1 AUC 0-6h Response

Adjusted means of forced expiratory volume in one second (FEV1) area under the curve (AUC) 0-3 hour and AUC 0-6 hour responses [L] after 4 weeks treatment calculated using the trapezoidal rule, divided by the duration (3 h, 6 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29

,,,,,,,
InterventionLitres (Mean)
AUC 0-3hAUC 0-6h
Olo 100.1910.198
Olo 50.1830.188
T+O 1.25/100.2880.296
T+O 1.25/50.2580.267
T+O 2.5/100.3190.320
T+O 2.5/50.2800.287
T+O 5/100.3340.342
T+O 5/50.3020.307

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Trough Forced Vital Capacity (FVC) Response

Adjusted means of trough FVC (forced vital capacity) response [L] after 4 weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29

InterventionLitres (Mean)
Olo 50.114
T+O 1.25/50.214
T+O 2.5/50.234
T+O 5/50.215
Olo 100.122
T+O 1.25/100.253
T+O 2.5/100.253
T+O 5/100.249

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Trough FEV1 Response

Adjusted means of the trough forced expiratory volume in one second (FEV1) response (L) after four weeks treatment. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements on day 29. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. (NCT01040403)
Timeframe: Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29

InterventionLitres (Mean)
Olo 50.071
T+O 1.25/50.125
T+O 2.5/50.136
T+O 5/50.155
Olo 100.083
T+O 1.25/100.134
T+O 2.5/100.166
T+O 5/100.163

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Pulse Rate Recorded in Conjunction With Spirometry

Pulse rate recorded in conjunction with spirometry change from baseline at 30 minutes post-dose on day 29 in beats per minute (bpm). (NCT01040403)
Timeframe: Baseline and 30 min post-dose on day 29

Interventionbpm (Mean)
Olo 5-2.4
T+O 1.25/5-2.8
T+O 2.5/5-3.1
T+O 5/5-1.8
Olo 10-2.1
T+O 1.25/10-3.6
T+O 2.5/10-2.4
T+O 5/10-1.0

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Peak FVC (0-3h) Response

Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose in first treatment period. Peak FVC (0-3h) was obtained within 0 - 3 hours after the last dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040689)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo0.086
Olo 5 mcg qd0.386
Olo 10 mcg qd0.383
Tio 18 mcg qd0.381

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FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose of first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040689)
Timeframe: 1 h and 10 min prior to dose on the first day of the first treatment period (study baseline) and 12 h, 22 h, 23 h, and 23 h 50 min relative to last dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.166
Olo 5 mcg qd0.030
Olo 10 mcg qd0.086
Tio 18 mcg qd0.018

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Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of first treatment period. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the last dose after six weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040689)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo0.019
Olo 5 mcg qd0.232
Olo 10 mcg qd0.253
Tio 18 mcg qd0.220

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FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment

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 for the first period, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040689)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of the first treatment period (study baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 12 h relative to am dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.054
Olo 5 mcg qd0.131
Olo 10 mcg qd0.152
Tio 18 mcg qd0.119

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FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment

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 for the first period, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040689)
Timeframe: 1 h and 10 min prior to am dose on the first day of the first treatment period (study baseline) and 12 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.095
Olo 5 mcg qd0.036
Olo 10 mcg qd0.082
Tio 18 mcg qd0.027

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After First Dose of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040689)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose of the first period (study baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the first dose of treatment period

InterventionLiter (Mean)
Placebo-0.021
Olo 5 mcg qd0.161
Olo 10 mcg qd0.191
Tio 18 mcg qd0.111

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the first visit of the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040689)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h, 4 h, 6h, 8h, 10h, 12 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.075
Olo 5 mcg qd0.083
Olo 10 mcg qd0.117
Tio 18 mcg qd0.073

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Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of first treatment period. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the first dose of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040689)
Timeframe: Study baseline and first day of dosing

InterventionLiter (Mean)
Placebo0.040
Olo 5 mcg qd0.253
Olo 10 mcg qd0.279
Tio 18 mcg qd0.201

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040689)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the last dose of treatment after six weeks of treatment.

InterventionLiter (Mean)
Placebo-0.045
Olo 5 mcg qd0.161
Olo 10 mcg qd0.170
Tio 18 mcg qd0.137

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Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose in first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040689)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the first treatment period (study baseline) and -30 min (zero time), 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12h relative to last dose after six weeks of treatment.

InterventionLiter (Mean)
Placebo-0.110
Olo 5 mcg qd0.172
Olo 10 mcg qd0.192
Tio 18 mcg qd0.166

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FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose in first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040689)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h, 4 h, 6h, 8h, 10h, 12 h, 22 h, 23 h, and 23 h 50 min relative to last dose after six weeks of treatment.

InterventionLiter (Mean)
Placebo-0.138
Olo 5 mcg qd0.101
Olo 10 mcg qd0.139
Tio 18 mcg qd0.091

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose in the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040689)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h relative to last dose after six weeks of treatment.

InterventionLiter (Mean)
Placebo-0.083
Olo 5 mcg qd0.234
Olo 10 mcg qd0.235
Tio 18 mcg qd0.219

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose in the first treatment period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040689)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of the treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h relative to first dose of treatment

InterventionLiter (Mean)
Placebo-0.024
Olo 5 mcg qd0.244
Olo 10 mcg qd0.288
Tio 18 mcg qd0.191

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

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). (NCT01040689)
Timeframe: 6 weeks

,,,
Interventionpercentage of participants (Number)
PalpitationsInvestigations
Olo 10 mcg1.00.0
Olo 5 mcg0.00.0
Placebo0.00.0
Tiotropium (Tio) 18 mcg qd0.00.0

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Trough FVC Response

Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values prior to first dose in first treatment period. Trough values were mean of the values obtained 23 h and 23 h 50 min after the last dose of study drug after six weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040689)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo-0.082
Olo 5 mcg qd0.103
Olo 10 mcg qd0.130
Tio 18 mcg qd0.046

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Trough FEV1 Response

Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values prior to first dose of first treatment period. Trough values were the mean of values obtained 23 hours and 23h 50min post the last dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040689)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo-0.043
Olo 5 mcg qd0.090
Olo 10 mcg qd0.104
Tio 18 mcg qd0.054

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Trough FEV1 Response

Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values prior to first dose of treatment for the first period. Trough values were the mean of values obtained 23h and 23 h 50 min after the last dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040728)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo0.003
Olo 5 mcg qd0.137
Olo 10 mcg qd0.146
Tio 18 mcg qd0.161

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FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose of treatment for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040728)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h, 4 h, 6h, 8h, 10h, 12 h, 22 h, 23 h, and 23 h 50 min relative to last dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.057
Olo 5 mcg qd0.247
Olo 10 mcg qd0.226
Tio 18 mcg qd0.278

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FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment

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 for the first period, just prior to administration of the first morning dose of randomized treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040728)
Timeframe: 1 hour (h) and 10 minutes (min) prior to the am dose on the first day of the first treatment period (study baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 12 h relative to am dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.008
Olo 5 mcg qd0.189
Olo 10 mcg qd0.213
Tio 18 mcg qd0.213

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Peak FVC (0-3h) Response

Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of treatment for the first period. 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 treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040728)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo0.191
Olo 5 mcg qd0.526
Olo 10 mcg qd0.537
Tio 18 mcg qd0.569

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Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of treatment for the first period. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the last dose after six weeks of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040728)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo0.082
Olo 5 mcg qd0.290
Olo 10 mcg qd0.325
Tio 18 mcg qd0.325

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Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of treatment for the first period. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after the first dose of treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040728)
Timeframe: Study baseline and first day of dosing

InterventionLiter (Mean)
Placebo0.076
Olo 5 mcg qd0.313
Olo 10 mcg qd0.342
Tio 18 mcg qd0.251

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FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose of treatment for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040728)
Timeframe: 1 h and 10 min prior to the am dose on the first day of the first treatment period (study baseline) and 12 h, 22 h, 23 h, and 23 h 50 min relative to last dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.109
Olo 5 mcg qd0.169
Olo 10 mcg qd0.155
Tio 18 mcg qd0.192

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of treatment for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040728)
Timeframe: 1 hour (h) and 10 minutes (min) prior to the am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h relative to last dose of treatment after six weeks of treatment

InterventionLiter (Mean)
Placebo0.044
Olo 5 mcg qd0.388
Olo 10 mcg qd0.397
Tio 18 mcg qd0.414

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FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of treatment for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040728)
Timeframe: 1 hour (h) and 10 minutes (min) prior to the am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h relative to first dose of treatment

InterventionLiter (Mean)
Placebo0.053
Olo 5 mcg qd0.423
Olo 10 mcg qd0.419
Tio 18 mcg qd0.316

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Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to first dose of treatment for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres. (NCT01040728)
Timeframe: 1 hour (h) and 10 minutes (min) prior to the am dose on the first day of the first treatment period (study baseline) and -30 min (zero time), 30 min, 60 min, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12h relative to last dose after six weeks of treatment.

InterventionLiter (Mean)
Placebo-0.006
Olo 5 mcg qd0.324
Olo 10 mcg qd0.321
Tio 18 mcg qd0.364

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of treatment for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040728)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to the am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the first dose of treatment after six weeks of treatment

InterventionLiter (Mean)
Placebo0.011
Olo 5 mcg qd0.225
Olo 10 mcg qd0.255
Tio 18 mcg qd0.246

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After First Dose of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of the treatment at the first treatment visit for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040728)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to the am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the first dose of treatment period

InterventionLiter (Mean)
Placebo0.018
Olo 5 mcg qd0.232
Olo 10 mcg qd0.256
Tio 18 mcg qd0.169

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose at the first randomized treatment visit for the first period. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040728)
Timeframe: 1 hour (h) and 10 minutes (min) prior to am dose on the first day of the first treatment period (study baseline) and -30 min, 30 min, 60 min, 2 h, 3 h, 4 h, 6h, 8h, 10h, 12 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.033
Olo 5 mcg qd0.142
Olo 10 mcg qd0.158
Tio 18 mcg qd0.159

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FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment

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 for the first period, just prior to administration of the first morning dose of randomized treatment. Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. 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. (NCT01040728)
Timeframe: 1 h and 10 min prior to the am dose on the first day of the first treatment period (study baseline) and 12 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

InterventionLiter (Mean)
Placebo-0.059
Olo 5 mcg qd0.094
Olo 10 mcg qd0.111
Tio 18 mcg qd0.105

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

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). (NCT01040728)
Timeframe: 6 weeks

,,,
Interventionparticipants (Number)
Potassium increasedAtrial fibrillationPalpitations
Olo 10 mcg011
Olo 5 mcg000
Placebo100
Tiotropium (Tio) 18 mcg qd000

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Trough FVC Response

Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values prior to first dose of treatment for the first period. Trough values were the mean of obtained 23 h and 23 h 50 min after the last dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with treatment and period as fixed effects and patient as a random effect and study baseline as a continuous covariate. (NCT01040728)
Timeframe: Study baseline and 6 weeks

InterventionLiter (Mean)
Placebo-0.001
Olo 5 mcg qd0.243
Olo 10 mcg qd0.215
Tio 18 mcg qd0.255

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Adjusted Mean Endurance Time After 6 Weeks

Primary endpoint was endurance time during constant work rate ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. Mixed effects model on log10 transformation data. Adjusted means are back transformed to report as geometric means. Standard errors (SEs) are calculated using the delta method. (NCT01040793)
Timeframe: 6 weeks

Interventionseconds (Geometric Mean)
Placebo354.33
Olo 5 mcg qd396.31
Olo 10 mcg qd391.45

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Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.577
Olo 5 mcg qd1.768
Olo 10 mcg qd1.771

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Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.520
Olo 5 mcg qd1.630
Olo 10 mcg qd1.630

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Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo3.144
Olo 5 mcg qd3.409
Olo 10 mcg qd3.425

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Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort. (NCT01040793)
Timeframe: 6 weeks

InterventionScores on a scale (Least Squares Mean)
Placebo7.010
Olo 5 mcg qd7.101
Olo 10 mcg qd7.351

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Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo3.103
Olo 5 mcg qd3.222
Olo 10 mcg qd3.222

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Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.158
Olo 5 mcg qd2.236
Olo 10 mcg qd2.330

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Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks

Measured using body plethysmography (NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo4.770
Olo 5 mcg qd4.557
Olo 10 mcg qd4.583

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Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks

Measured using body plethysmography (NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo4.842
Olo 5 mcg qd4.757
Olo 10 mcg qd4.723

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Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.493
Olo 5 mcg qd2.725
Olo 10 mcg qd2.696

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Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks

"Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.~Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort." (NCT01040793)
Timeframe: 6 weeks

InterventionScores on a scale (Least Squares Mean)
Placebo5.585
Olo 5 mcg qd5.250
Olo 10 mcg qd5.520

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Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort. (NCT01040793)
Timeframe: 6 weeks

InterventionScores on a scale (Least Squares Mean)
Placebo0.389
Olo 5 mcg qd0.315
Olo 10 mcg qd0.364

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Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks

Measured using body plethysmography (NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.463
Olo 5 mcg qd2.613
Olo 10 mcg qd2.618

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Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks

Measured using body plethysmography (NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo7.311
Olo 5 mcg qd7.368
Olo 10 mcg qd7.340

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Change From Baseline to Day 43 in Pulse Rate

Change from Baseline to Day 43 in Pulse rate with spirometry. Baseline is defined as mean of pre-treatment values at a given time point. (NCT01040793)
Timeframe: Baseline and Week 6

Interventionbeats/min (Mean)
Placebo-2.3
Olo 5 mcg-1.8
Olo 10 mcg-1.6

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Change From Baseline to Day 43 in Blood Pressure

Change from Baseline to Day 43 in Blood Pressure with spirometry. Baseline is defined as mean of pre-treatment values at a given time point. (NCT01040793)
Timeframe: Baseline and Week 6

,,
InterventionmmHg (Mean)
Systolic blood pressureDiastolic blood pressure
Olo 10 mcg-1.4-2.2
Olo 5 mcg-1.5-1.8
Placebo-0.5-0.8

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Number of Patients With Notable Changes in Heart Rate

Number of Patients with notable changes in heart rate (HR). Notable HR increase defined as >=25% increase and on-treatment HR > 100 bpm; Notable HR decrease defined as >=25% decrease and on-treatment HR < 50 bpm. (NCT01040793)
Timeframe: Baseline and Week 6

,,
Interventionpercentage of participants (Number)
30 min pre-dose: increase30 min pre-dose: decrease30 min pre-dose: no notable change40 min post-dose: increase (N=147,142,140)40 min post-dose: decrease (N=147,142,140)40 min post-dose: no notable change(N=147,142,140)
Olo 10 mcg0.02.997.10.03.696.4
Olo 5 mcg0.71.497.90.04.295.8
Placebo0.70.798.60.00.799.3

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Number of Patients With Notable Increase in PR Intervals

Number of Patients with notable increase in PR intervals. Notable PR interval increase defined as >=25% increase and on-treatment PR interval > 200 ms. (NCT01040793)
Timeframe: Baseline and Week 6

,,
Interventionpercentage of participants (Number)
30 min pre-dose: increase30 min pre-dose: no increase40 min post-dose: increase (N=147, 142, 140)40 min post-dose: no increase (N=147, 142, 140)
Olo 10 mcg0.0100.00.0100.0
Olo 5 mcg0.0100.00.0100.0
Placebo0.0100.00.799.3

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Number of Patients With Notable Increase in QRS Intervals

Number of Patients with notable increase in QRS intervals. Notable QRS interval increase defined as >=10% increase and on-treatment QRS interval > 110 ms. (NCT01040793)
Timeframe: Baseline and Week 6

,,
Interventionpercentage of participants (Number)
30 min pre-dose: increase30 min pre-dose: no increase40 min post-dose: increase (N=147, 142, 140)40 min post-dose: no increase (N=147, 142, 140)
Olo 10 mcg0.799.30.799.3
Olo 5 mcg0.799.30.799.3
Placebo0.799.31.498.6

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Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks

Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods. (NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.162
Olo 5 mcg qd2.246
Olo 10 mcg qd2.328

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Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.273
Olo 5 mcg qd2.437
Olo 10 mcg qd2.468

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Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters/second (Least Squares Mean)
Placebo4.324
Olo 5 mcg qd4.904
Olo 10 mcg qd4.876

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Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks

(NCT01040793)
Timeframe: 6 weeks

Interventionliters/second (Least Squares Mean)
Placebo4.258
Olo 5 mcg qd4.539
Olo 10 mcg qd4.549

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Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks

Measured using body plethysmography (NCT01040793)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo7.262
Olo 5 mcg qd7.285
Olo 10 mcg qd7.272

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Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

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. (NCT01311661)
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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo-0.004
Olo 2.5 mcg Bid0.132
Olo 5 mcg qd0.119
Olo 5 mcg Bid0.138
Olo 10 mcg qd0.143

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FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

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. (NCT01311661)
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo-0.029
Olo 2.5 mcg Bid0.116
Olo 5 mcg qd0.099
Olo 5 mcg Bid0.127
Olo 10 mcg qd0.111

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FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

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. (NCT01311661)
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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo-0.056
Olo 2.5 mcg Bid0.102
Olo 5 mcg qd0.081
Olo 5 mcg Bid0.114
Olo 10 mcg qd0.079

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Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 Hours (AUC 0-24h) Response at the End of Each Treatment Period

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. (NCT01311661)
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, 6 h, 8 h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo0.022
Olo 2.5 mcg Bid0.213
Olo 5 mcg qd0.173
Olo 5 mcg Bid0.250
Olo 10 mcg qd0.231

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Peak FVC Within 24 Hours Post-dose Response

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 morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo0.246
Olo 2.5 mcg Bid0.382
Olo 5 mcg qd0.371
Olo 5 mcg Bid0.390
Olo 10 mcg qd0.373

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Peak PEF Within 24 Hours Post-dose Response

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 morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter/sec (Mean)
Placebo0.663
Olo 2.5 mcg Bid1.254
Olo 5 mcg qd1.185
Olo 5 mcg Bid1.257
Olo 10 mcg qd1.286

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Number of Patients Categorized by Worst Asthma Nighttime Symptoms (Overall)

Assessed by patients at home using the AM3 device during each period of randomised treatment. (NCT01311661)
Timeframe: 0-3 weeks

,,,,
InterventionNumber of patients (Number)
No asthma symptomsMild asthma symptomsModerate asthma symptomsSevere asthma symptomsVery severe asthma symptoms
Olo 10 mcg qd21403532
Olo 2.5 mcg Bid32352642
Olo 5 mcg Bid21482921
Olo 5 mcg qd29383210
Placebo39767493

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PEF Area Under Curve 12-24 Hours (AUC 12-24h) Response

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. (NCT01311661)
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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter/sec (Mean)
Placebo-0.135
Olo 2.5 mcg Bid0.530
Olo 5 mcg qd0.430
Olo 5 mcg Bid0.567
Olo 10 mcg qd0.464

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PEF Daily Variability

PEF daily variability was assessed by patients at home using the AM3 device (overall means obtained during each period of randomised treatment 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. (NCT01311661)
Timeframe: 0-3 weeks

InterventionPercentage (Mean)
Placebo10.157
Olo 2.5 mcg Bid8.576
Olo 5 mcg qd8.732
Olo 5 mcg Bid8.419
Olo 10 mcg qd9.468

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Percentage of Asthma Symptom Free Days

Percentage of asthma-symptom free days 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 AM3 device. (NCT01311661)
Timeframe: 0-3 weeks

InterventionPercentage of asthma symptom free days (Mean)
Placebo23.630
Olo 2.5 mcg Bid33.929
Olo 5 mcg qd36.306
Olo 5 mcg Bid28.844
Olo 10 mcg qd28.049

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FEV1 Area Under Curve 0-12 Hours (AUC 0-12h) Response at the End of Each Treatment Period

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. (NCT01311661)
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, 6 h, 8 h, 10 h, 11 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo0.052
Olo 2.5 mcg Bid0.242
Olo 5 mcg qd0.212
Olo 5 mcg Bid0.266
Olo 10 mcg qd0.272

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FEV1 Area Under Curve 12-24 Hours (AUC 12-24h) Response at the End of Each Treatment Period

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. (NCT01311661)
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, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo-0.010
Olo 2.5 mcg Bid0.186
Olo 5 mcg qd0.135
Olo 5 mcg Bid0.233
Olo 10 mcg qd0.189

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Peak FEV1 Within 24 Hours Post-dose Response

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 morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo0.227
Olo 2.5 mcg Bid0.410
Olo 5 mcg qd0.380
Olo 5 mcg Bid0.449
Olo 10 mcg qd0.437

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Peak Expiratory Flow (PEF) Area Under Curve 0-24 Hours (AUC 0-24h) Response

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. (NCT01311661)
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, 6 h, 8h, 10 h, 11 h 50 min, 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter/sec (Mean)
Placebo-0.014
Olo 2.5 mcg Bid0.627
Olo 5 mcg qd0.563
Olo 5 mcg Bid0.653
Olo 10 mcg qd0.629

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Peak Expiratory Flow (PEF) Area Under Curve 0-12 Hours (AUC 0-12h) Response

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. (NCT01311661)
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, 6 h, 8h, 10 h, 11 h 50 min related to morning dose after 3 weeks

InterventionLiter/sec (Mean)
Placebo0.101
Olo 2.5 mcg Bid0.730
Olo 5 mcg qd0.703
Olo 5 mcg Bid0.732
Olo 10 mcg qd0.787

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Number of Patients Categorized by Worst Asthma Daytime Symptoms (Overall)

Assessed by patients at home using the AM3 device during each period of randomised treatment . (NCT01311661)
Timeframe: 0-3 weeks

,,,,
InterventionNumber of patients (Number)
No asthma symptomsMild asthma symptomsModerate asthma symptomsSevere asthma symptomsVery severe asthma symptoms
Olo 10 mcg qd20413721
Olo 2.5 mcg Bid24452541
Olo 5 mcg Bid18423641
Olo 5 mcg qd27422731
Placebo316685181

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Number of Patients Categorized by Highest Number of Night Time Awakenings (Overall)

Assessed by patients at home using the AM3 device during each period of randomised treatment. (NCT01311661)
Timeframe: 0-3 weeks

,,,,
InterventionNumber of patients (Number)
Did not wake upWoke up onceWoke up 2-5 timesWoke up > 5 timesWas awake all night
Olo 10 mcg qd47321921
Olo 2.5 mcg Bid50311800
Olo 5 mcg Bid44411402
Olo 5 mcg qd53361010
Placebo93673650

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Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

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. Time frame for adverse event reporting includes 12 days into the subsequent washout or post-treatment period. (NCT01311661)
Timeframe: 3 weeks + 12 days

,,,,
InterventionParticipants (Number)
Atrioventricular block first degreeSinus tachycardiaAspartate aminotransferase increasedBlood creatinine increasedBlood glucose increasedBlood urea abnormalGamma-glutamyltransferase increasedBlood creatine phosphokinase increasedBlood urine presentAnaemiaHypertension
Olo 10 mcg qd00101010000
Olo 2.5 mcg Bid00000000000
Olo 5 mcg Bid00000000012
Olo 5 mcg qd10010100000
Placebo01000001100

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Trough PEF Response

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 PEF values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter/sec (Mean)
Placebo-0.009
Olo 2.5 mcg Bid0.520
Olo 5 mcg qd0.401
Olo 5 mcg Bid0.594
Olo 10 mcg qd0.472

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Trough FVC Response

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 FVC values performed at 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo-0.013
Olo 2.5 mcg Bid0.096
Olo 5 mcg qd0.079
Olo 5 mcg Bid0.105
Olo 10 mcg qd0.098

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Trough FEV1 Response

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 23 h and 23 h 50 min after the last morning trial drug inhalation at the end of each 3 week period of randomised treatment. Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and 23 h, and 23 h 50 min related to morning dose after 3 weeks

InterventionLiter (Mean)
Placebo0.033
Olo 2.5 mcg Bid0.189
Olo 5 mcg qd0.134
Olo 5 mcg Bid0.229
Olo 10 mcg qd0.205

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Total Asthma Control Questionnaire (ACQ) Score

Control of asthma as assessed by the ACQ at the end of each 3-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. (NCT01311661)
Timeframe: 3 weeks

InterventionUnits on a scale (Mean)
Placebo1.613
Olo 2.5 mcg Bid1.256
Olo 5 mcg qd1.317
Olo 5 mcg Bid1.312
Olo 10 mcg qd1.311

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Mean Pre-dose Morning PEF (PEF a.m.)

PEF a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 0-3 weeks

InterventionLiter/min (Mean)
Placebo395.36
Olo 2.5 mcg Bid428.32
Olo 5 mcg qd427.99
Olo 5 mcg Bid427.02
Olo 10 mcg qd424.26

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Mean Pre-dose Morning FEV1 (FEV1 a.m.)

FEV1 a.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 0-3 weeks

InterventionmL (Mean)
Placebo2425.1
Olo 2.5 mcg Bid2598.5
Olo 5 mcg qd2580.2
Olo 5 mcg Bid2574.3
Olo 10 mcg qd2575.5

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Mean Pre-dose Evening PEF (PEF p.m.)

PEF p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 0-3 weeks

InterventionLiter/min (Mean)
Placebo409.93
Olo 2.5 mcg Bid438.80
Olo 5 mcg qd441.98
Olo 5 mcg Bid441.74
Olo 10 mcg qd443.25

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Mean Pre-dose Evening FEV1 (FEV1 p.m.)

FEV1 p.m. was measured by patients at home using the AM3 device (overall means obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 0-3 weeks

InterventionmL (Mean)
Placebo2474.3
Olo 2.5 mcg Bid2616.6
Olo 5 mcg qd2606.5
Olo 5 mcg Bid2616.5
Olo 10 mcg qd2631.7

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Mean Number of Puffs of Rescue Medication During the Whole Day

Mean of daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Assessed by patients at home using the AM3 device (overall mean number obtained during each period of randomised treatment will be compared). Means are adjusted for treatment, period, patient and study baseline. (NCT01311661)
Timeframe: 0-3 weeks

InterventionPuffs (Mean)
Placebo1.665
Olo 2.5 mcg Bid1.110
Olo 5 mcg qd1.028
Olo 5 mcg Bid1.077
Olo 10 mcg qd1.119

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FEV1 AUC(0-3h) Response on Day 1

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.205
Tiotropium (2.5 μg)0.148
Tiotropium (5 μg)0.157
Tio+Olo FDC (2.5/5 μg)0.226
Tio+Olo FDC (5/5 μg)0.237

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FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.~Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.108
Tiotropium (2.5 μg)0.083
Tiotropium (5 μg)0.100
Tio+Olo FDC (2.5/5 μg)0.159
Tio+Olo FDC (5/5 μg)0.206

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FEV1 AUC(0-12h) Response in the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.~Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.131
Tiotropium (2.5 μg)0.109
Tiotropium (5 μg)0.127
Tio+Olo FDC (2.5/5 μg)0.202
Tio+Olo FDC (5/5 μg)0.250

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Trough FEV1 Response on Day 15.

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed~1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.085
Tiotropium (2.5 μg)0.101
Tiotropium (5 μg)0.094
Tio+Olo FDC (2.5/5 μg)0.132
Tio+Olo FDC (5/5 μg)0.157

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Trough FVC Response on Day 85.

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.077
Tiotropium (2.5 μg)0.168
Tiotropium (5 μg)0.144
Tio+Olo FDC (2.5/5 μg)0.230
Tio+Olo FDC (5/5 μg)0.265

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Trough FVC Response on Day 43.

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.150
Tiotropium (2.5 μg)0.206
Tiotropium (5 μg)0.213
Tio+Olo FDC (2.5/5 μg)0.254
Tio+Olo FDC (5/5 μg)0.318

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Trough FVC Response on Day 365.

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on Day 365.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.014
Tiotropium (2.5 μg)0.114
Tiotropium (5 μg)0.108
Tio+Olo FDC (2.5/5 μg)0.155
Tio+Olo FDC (5/5 μg)0.191

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Trough FVC Response on Day 170.

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FVC measurements performed at 23h and at 23h 50 min after inhalation of study medication at the clinic visit on the previous day.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.093
Tiotropium (2.5 μg)0.184
Tiotropium (5 μg)0.169
Tio+Olo FDC (2.5/5 μg)0.225
Tio+Olo FDC (5/5 μg)0.246

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Trough FVC Response on Day 15.

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.149
Tiotropium (2.5 μg)0.222
Tiotropium (5 μg)0.220
Tio+Olo FDC (2.5/5 μg)0.270
Tio+Olo FDC (5/5 μg)0.296

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Trough FEV1 Response on Day 85

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed~1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 85.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.057
Tiotropium (2.5 μg)0.077
Tiotropium (5 μg)0.070
Tio+Olo FDC (2.5/5 μg)0.128
Tio+Olo FDC (5/5 μg)0.146

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Trough FEV1 Response on Day 43

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed~1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.083
Tiotropium (2.5 μg)0.097
Tiotropium (5 μg)0.088
Tio+Olo FDC (2.5/5 μg)0.120
Tio+Olo FDC (5/5 μg)0.163

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Trough FEV1 Response on Day 365

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed~1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 365

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)-0.000
Tiotropium (2.5 μg)0.028
Tiotropium (5 μg)0.036
Tio+Olo FDC (2.5/5 μg)0.075
Tio+Olo FDC (5/5 μg)0.099

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Trough FEV1 Response on Day 170.

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FEV1 measurements performed at 23 h and at 23 h 50 min after inhalation of study medication at the clinic visit on the previous day.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.054
Tiotropium (2.5 μg)0.083
Tiotropium (5 μg)0.065
Tio+Olo FDC (2.5/5 μg)0.111
Tio+Olo FDC (5/5 μg)0.136

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Trough FEV1 Response on Day 169

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed~1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on Day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.033
Tiotropium (2.5 μg)0.047
Tiotropium (5 μg)0.050
Tio+Olo FDC (2.5/5 μg)0.094
Tio+Olo FDC (5/5 μg)0.112

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Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. (NCT01431274)
Timeframe: Day 85

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)38.832
Tiotropium (2.5 μg)37.821
Tiotropium (5 μg)37.822
Tio+Olo FDC (2.5/5 μg)37.304
Tio+Olo FDC (5/5 μg)36.691

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Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. (NCT01431274)
Timeframe: Day 365

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)38.989
Tiotropium (2.5 μg)37.609
Tiotropium (5 μg)37.581
Tio+Olo FDC (2.5/5 μg)37.553
Tio+Olo FDC (5/5 μg)37.138

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Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group. (NCT01431274)
Timeframe: Day 169

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)38.366
Tiotropium (2.5 μg)37.792
Tiotropium (5 μg)37.907
Tio+Olo FDC (2.5/5 μg)37.335
Tio+Olo FDC (5/5 μg)36.674

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"Mahler Transitional Dyspnoea Index (TDI) focal score on Day 85 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431274)
Timeframe: Day 85

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.506
Tiotropium (2.5 μg)1.698
Tiotropium (5 μg)1.702
Tio+Olo FDC (2.5/5 μg)1.925
Tio+Olo FDC (5/5 μg)2.136

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"Mahler Transitional Dyspnoea Index (TDI) focal score on Day 43 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431274)
Timeframe: Day 43

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.453
Tiotropium (2.5 μg)1.430
Tiotropium (5 μg)1.408
Tio+Olo FDC (2.5/5 μg)1.876
Tio+Olo FDC (5/5 μg)2.048

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"Mahler Transitional Dyspnoea Index (TDI) focal score on Day 365 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287).~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431274)
Timeframe: Day 365

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.411
Tiotropium (2.5 μg)1.450
Tiotropium (5 μg)1.736
Tio+Olo FDC (2.5/5 μg)1.782
Tio+Olo FDC (5/5 μg)2.058

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, present 1237.5 (NCT01431274) and 1237.6 (NCT01431287) is the key secondary endpoint.~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431274)
Timeframe: Day 169

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.564
Tiotropium (2.5 μg)1.690
Tiotropium (5 μg)1.627
Tio+Olo FDC (2.5/5 μg)1.980
Tio+Olo FDC (5/5 μg)1.983

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FVC AUC(0-24h) Response in Sub-set of Patients With 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.~FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.~Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.192
Tiotropium (2.5 μg)0.141
Tiotropium (5 μg)0.203
Tio+Olo FDC (2.5/5 μg)0.297
Tio+Olo FDC (5/5 μg)0.329

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FVC AUC(0-12h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)

"FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.227
Tiotropium (2.5 μg)0.180
Tiotropium (5 μg)0.248
Tio+Olo FDC (2.5/5 μg)0.356
Tio+Olo FDC (5/5 μg)0.388

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FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.247
Tiotropium (2.5 μg)0.318
Tiotropium (5 μg)0.275
Tio+Olo FDC (2.5/5 μg)0.432
Tio+Olo FDC (5/5 μg)0.469

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FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.172
Tiotropium (2.5 μg)0.241
Tiotropium (5 μg)0.221
Tio+Olo FDC (2.5/5 μg)0.364
Tio+Olo FDC (5/5 μg)0.377

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FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.212
Tiotropium (2.5 μg)0.279
Tiotropium (5 μg)0.254
Tio+Olo FDC (2.5/5 μg)0.386
Tio+Olo FDC (5/5 μg)0.407

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FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.350
Tiotropium (2.5 μg)0.277
Tiotropium (5 μg)0.289
Tio+Olo FDC (2.5/5 μg)0.400
Tio+Olo FDC (5/5 μg)0.427

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Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the MMRM model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.133
Tiotropium (2.5 μg)0.148
Tiotropium (5 μg)0.139
Tio+Olo FDC (2.5/5 μg)0.241
Tio+Olo FDC (5/5 μg)0.256

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FEV1 AUC(0-3h) Response on Day 85

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.161
Tiotropium (2.5 μg)0.176
Tiotropium (5 μg)0.162
Tio+Olo FDC (2.5/5 μg)0.271
Tio+Olo FDC (5/5 μg)0.289

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FEV1 AUC(0-3h) Response on Day 365

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431274)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365.

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.096
Tiotropium (2.5 μg)0.116
Tiotropium (5 μg)0.122
Tio+Olo FDC (2.5/5 μg)0.214
Tio+Olo FDC (5/5 μg)0.237

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Trough FEV1 Response on Day 43

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.070
Tiotropium (2.5 μg)0.085
Tiotropium (5 μg)0.103
Tio+Olo FDC (2.5/5 μg)0.146
Tio+Olo FDC (5/5 μg)0.150

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Trough FVC Response on Day 365

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 365

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.028
Tiotropium (2.5 μg)0.096
Tiotropium (5 μg)0.097
Tio+Olo FDC (2.5/5 μg)0.198
Tio+Olo FDC (5/5 μg)0.184

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Trough FVC Response on Day 43

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.129
Tiotropium (2.5 μg)0.206
Tiotropium (5 μg)0.222
Tio+Olo FDC (2.5/5 μg)0.281
Tio+Olo FDC (5/5 μg)0.293

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FVC AUC(0-12h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.227
Tiotropium (2.5 μg)0.180
Tiotropium (5 μg)0.248
Tio+Olo FDC (2.5/5 μg)0.356
Tio+Olo FDC (5/5 μg)0.388

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FVC AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.~FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.~Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.192
Tiotropium (2.5 μg)0.141
Tiotropium (5 μg)0.203
Tio+Olo FDC (2.5/5 μg)0.297
Tio+Olo FDC (5/5 μg)0.329

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) is the key secondary endpoint.~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 169

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.564
Tiotropium (2.5 μg)1.690
Tiotropium (5 μg)1.627
Tio+Olo FDC (2.5/5 μg)1.980
Tio+Olo FDC (5/5 μg)1.983

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"Mahler TDI focal score on Day 365 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 365

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.411
Tiotropium (2.5 μg)1.450
Tiotropium (5 μg)1.736
Tio+Olo FDC (2.5/5 μg)1.782
Tio+Olo FDC (5/5 μg)2.058

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"Mahler TDI focal score on Day 43 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 43

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.453
Tiotropium (2.5 μg)1.430
Tiotropium (5 μg)1.408
Tio+Olo FDC (2.5/5 μg)1.876
Tio+Olo FDC (5/5 μg)2.048

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Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the MMRM model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.136
Tiotropium (2.5 μg)0.125
Tiotropium (5 μg)0.165
Tio+Olo FDC (2.5/5 μg)0.256
Tio+Olo FDC (5/5 μg)0.268

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Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"Mahler TDI focal score on Day 85 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).~The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 85

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)1.506
Tiotropium (2.5 μg)1.698
Tiotropium (5 μg)1.702
Tio+Olo FDC (2.5/5 μg)1.925
Tio+Olo FDC (5/5 μg)2.136

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Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).

"The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 169

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)38.366
Tiotropium (2.5 μg)37.792
Tiotropium (5 μg)37.907
Tio+Olo FDC (2.5/5 μg)37.335
Tio+Olo FDC (5/5 μg)36.674

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Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 365

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)38.989
Tiotropium (2.5 μg)37.609
Tiotropium (5 μg)37.581
Tio+Olo FDC (2.5/5 μg)37.553
Tio+Olo FDC (5/5 μg)37.138

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FEV1 AUC(0-12h) Response in Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.~Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.131
Tiotropium (2.5 μg)0.109
Tiotropium (5 μg)0.127
Tio+Olo FDC (2.5/5 μg)0.202
Tio+Olo FDC (5/5 μg)0.250

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Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 169

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169

InterventionLitres (Median)
Olodaterol (5 μg)0.231
Tiotropium (2.5 μg)0.247
Tiotropium (5 μg)0.283
Tio+Olo FDC (2.5/5 μg)0.439
Tio+Olo FDC (5/5 μg)0.429

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FEV1 AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate.~Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.108
Tiotropium (2.5 μg)0.083
Tiotropium (5 μg)0.100
Tio+Olo FDC (2.5/5 μg)0.159
Tio+Olo FDC (5/5 μg)0.206

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FEV1 AUC(0-3h) Response on Day 1

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.196
Tiotropium (2.5 μg)0.135
Tiotropium (5 μg)0.164
Tio+Olo FDC (2.5/5 μg)0.228
Tio+Olo FDC (5/5 μg)0.229

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FEV1 AUC(0-3h) Response on Day 365

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.105
Tiotropium (2.5 μg)0.105
Tiotropium (5 μg)0.124
Tio+Olo FDC (2.5/5 μg)0.223
Tio+Olo FDC (5/5 μg)0.237

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FEV1 AUC(0-3h) Response on Day 85

"FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.153
Tiotropium (2.5 μg)0.165
Tiotropium (5 μg)0.187
Tio+Olo FDC (2.5/5 μg)0.272
Tio+Olo FDC (5/5 μg)0.297

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Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 1

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment

InterventionLitres (Median)
Olodaterol (5 μg)0.341
Tiotropium (2.5 μg)0.264
Tiotropium (5 μg)0.298
Tio+Olo FDC (2.5/5 μg)0.411
Tio+Olo FDC (5/5 μg)0.397

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Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 365

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365

InterventionLitres (Median)
Olodaterol (5 μg)0.180
Tiotropium (2.5 μg)0.216
Tiotropium (5 μg)0.198
Tio+Olo FDC (2.5/5 μg)0.397
Tio+Olo FDC (5/5 μg)0.381

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Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)

"The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group." (NCT01431287)
Timeframe: Day 85

Interventionpoints on a scale (Least Squares Mean)
Olodaterol (5 μg)38.832
Tiotropium (2.5 μg)37.821
Tiotropium (5 μg)37.822
Tio+Olo FDC (2.5/5 μg)37.304
Tio+Olo FDC (5/5 μg)36.691

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Trough FEV1 Response on Day 15

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.083
Tiotropium (2.5 μg)0.085
Tiotropium (5 μg)0.112
Tio+Olo FDC (2.5/5 μg)0.147
Tio+Olo FDC (5/5 μg)0.148

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Trough FEV1 Response on Day 169

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 169

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.034
Tiotropium (2.5 μg)0.041
Tiotropium (5 μg)0.068
Tio+Olo FDC (2.5/5 μg)0.111
Tio+Olo FDC (5/5 μg)0.119

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Trough FEV1 Response on Day 170

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FEV1 measurements performed at 23 h and at 23 h 50 min after inhalation of study medication at the clinic visit on the previous day.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.057
Tiotropium (2.5 μg)0.062
Tiotropium (5 μg)0.096
Tio+Olo FDC (2.5/5 μg)0.125
Tio+Olo FDC (5/5 μg)0.145

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Trough FEV1 Response on Day 365

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 365

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.011
Tiotropium (2.5 μg)0.022
Tiotropium (5 μg)0.040
Tio+Olo FDC (2.5/5 μg)0.077
Tio+Olo FDC (5/5 μg)0.093

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Trough FEV1 Response on Day 85

"Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 85

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.047
Tiotropium (2.5 μg)0.081
Tiotropium (5 μg)0.088
Tio+Olo FDC (2.5/5 μg)0.129
Tio+Olo FDC (5/5 μg)0.147

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Trough FVC Response on Day 15

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.163
Tiotropium (2.5 μg)0.209
Tiotropium (5 μg)0.222
Tio+Olo FDC (2.5/5 μg)0.293
Tio+Olo FDC (5/5 μg)0.285

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Trough FVC Response on Day 85

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.063
Tiotropium (2.5 μg)0.178
Tiotropium (5 μg)0.184
Tio+Olo FDC (2.5/5 μg)0.246
Tio+Olo FDC (5/5 μg)0.274

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Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 85

"FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres.~FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85

InterventionLitres (Median)
Olodaterol (5 μg)0.250
Tiotropium (2.5 μg)0.306
Tiotropium (5 μg)0.326
Tio+Olo FDC (2.5/5 μg)0.460
Tio+Olo FDC (5/5 μg)0.469

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Trough FVC Response on Day 170

"Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FVC measurements performed at 23h and at 23h 50 min after inhalation of study medication at the clinic visit on the previous day.~Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1).~The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.~Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group." (NCT01431287)
Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23h and at 23h 50 min after inhalation of study medication on day 170

InterventionLitres (Least Squares Mean)
Olodaterol (5 μg)0.116
Tiotropium (2.5 μg)0.163
Tiotropium (5 μg)0.202
Tio+Olo FDC (2.5/5 μg)0.266
Tio+Olo FDC (5/5 μg)0.274

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Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 12

"Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment.~The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results." (NCT01525615)
Timeframe: 12 weeks

Interventionunits / seconds (Least Squares Mean)
Placebo0.015
Tio+Olo 2.5 / 5.0 µg0.013
Tio+Olo 5.0 / 5.0 µg0.013

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Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks

Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 6 weeks of treatment. (NCT01525615)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo2.402
Tio+Olo 2.5 / 5.0 µg2.589
Tio+Olo 5.0 / 5.0 µg2.627

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Adjusted Mean Inspiratory Capacity at Pre-exercise After 12 Weeks

Secondary endpoint was pre-exercise inspiratory capacity (IC) before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) after 12 weeks of treatment. (NCT01525615)
Timeframe: 12 weeks

Interventionliters (Least Squares Mean)
Placebo2.390
Tio+Olo 2.5 / 5.0 µg2.597
Tio+Olo 5.0 / 5.0 µg2.624

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Adjusted Mean Inspiratory Capacity at Pre-exercise After 1 Day

Secondary endpoint was pre-exercise inspiratory capacity (IC) during constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap) on Day 1. (NCT01525615)
Timeframe: 1 day

Interventionliters (Least Squares Mean)
Placebo2.440
Tio+Olo 2.5 / 5.0 µg2.642
Tio+Olo 5.0 / 5.0 µg2.605

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Adjusted Mean Endurance Time During Endurance Shuttle Walk Test (ESWT) After 12 Weeks

Key secondary endpoint was endurance time during endurance shuttle walk test to symptom limitation at 85% of predicted maximum oxygen consumption (VO2) peak after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean. (NCT01525615)
Timeframe: 12 weeks

Interventionseconds (Least Squares Mean)
Placebo311.41
Tio+Olo 2.5 / 5.0 µg377.20
Tio+Olo 5.0 / 5.0 µg376.39

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Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) on Day 1

Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity on Day 1. Analysis of covariance model on log10 transformation data. Adjusted means are back transformed to report in original units. Standard errors (SEs) are calculated using the delta method. (NCT01525615)
Timeframe: 1 day

Interventionseconds (Least Squares Mean)
Placebo478.59
Tio+Olo 2.5 / 5.0 µg527.69
Tio+Olo 5.0 / 5.0 µg538.76

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Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 12 Weeks

Primary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 12 weeks of treatment. The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean. (NCT01525615)
Timeframe: 12 weeks

Interventionseconds (Least Squares Mean)
Placebo463.63
Tio+Olo 2.5 / 5.0 µg503.64
Tio+Olo 5.0 / 5.0 µg527.51

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Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) on Day 1

Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed on day 1 (NCT01525615)
Timeframe: 1 day

Interventionliters (Least Squares Mean)
Placebo1.509
Tio+Olo 2.5 / 5.0 µg1.693
Tio+Olo 5.0 / 5.0 µg1.679

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Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 6 Weeks

Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 6 weeks of treatment (NCT01525615)
Timeframe: 6 weeks

Interventionliters (Least Squares Mean)
Placebo1.517
Tio+Olo 2.5 / 5.0 µg1.790
Tio+Olo 5.0 / 5.0 µg1.763

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Adjusted Mean 1-hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 12 Weeks

Secondary endpoint was adjusted mean 1-hour, post-dose Forced Expiratory Volume in one second (FEV1) observed after 12 weeks of treatment (NCT01525615)
Timeframe: 12 weeks

Interventionliters (Least Squares Mean)
Placebo1.527
Tio+Olo 2.5 / 5.0 µg1.784
Tio+Olo 5.0 / 5.0 µg1.778

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Adjusted Mean Endurance Time During Constant Work Rate Cycle Ergometry (CWRCE) After 6 Weeks Treatment

Secondary endpoint was endurance time during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment.The endurance time in seconds was transformed using log10 scale to correct skewness in endurance time on original scale and then the MMRM model was fitted to the log10-transformed data and the least square means and SEs were obtained. To present the results in a way easier for interpretation, the least square mean from the MMRM fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate for the log10 of geometric mean and the corresponding SE was transformed using delta method to get the corresponding SEs of the geometric mean. (NCT01525615)
Timeframe: 6 weeks

Interventionseconds (Least Squares Mean)
Placebo427.74
Tio+Olo 2.5 / 5.0 µg522.26
Tio+Olo 5.0 / 5.0 µg525.62

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Adjusted Mean Slope of the Intensity of Breathing Discomfort on Day 1

"Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 1 day of treatment.~The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates slowing down in decline in breathing, i.e., favorable results." (NCT01525615)
Timeframe: 1 day

Interventionunits / seconds (Least Squares Mean)
Placebo0.014
Tio+Olo 2.5 / 5.0 µg0.012
Tio+Olo 5.0 / 5.0 µg0.012

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Adjusted Mean Slope of the Intensity of Breathing Discomfort After Week 6

"Secondary endpoint was the slope of the intensity of breathing discomfort during constant work rate cycle ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment.~The intensity of breathing discomfort was rated on the Borg Scale with categories from 0 (nothing at all) to 10 (maximal). The slope of the intensity of breathing discomfort was defined as the Borg scale value of breathing discomfort at the end of exercise minus the Borg scale value of breathing discomfort at pre-exercise divided by the endurance time. A decrease in slope indicates favorable results." (NCT01525615)
Timeframe: 6 weeks

Interventionunits / seconds (Least Squares Mean)
Placebo0.016
Tio+Olo 2.5 / 5.0 µg0.013
Tio+Olo 5.0 / 5.0 µg0.013

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Slope of the Intensity of Breathing Discomfort During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity

"Slope of the intensity of breathing discomfort during Constant Work Rate Cycle Ergometry (CWRCE) to symptom limitation at 75% Work capacity (Wcap). The intensity of breathing discomfort was rated using the modified Borg scale with ratings from 0 (nothing at all) to 10 (maximal).~Slope of breathing discomfort is defined as: (intensity of breathing discomfort at the end of exercise minus intensity of breathing discomfort at rest) / endurance time.~A decrease in slope indicates improvement.~The presented means are adjusted means from MMRM model." (NCT01533922)
Timeframe: 6 weeks

Interventionunits on a scale / second (Mean)
Placebo0.018
Olodaterol 5 µg0.016
Tiotropium 5 µg0.016
Tiotropium + Olodaterol 2.5/50.015
Tiotropium + Olodaterol 5/50.016

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Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap

"Endurance time during constant work rate cycle ergometry (CWRCE) to symptom limitation at 75% work capacity (Wcap).~Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.~The presented means are adjusted mean from the MMRM model." (NCT01533922)
Timeframe: 6 weeks

Interventionseconds (Geometric Mean)
Placebo375.45
Olodaterol 5 µg453.38
Tiotropium 5 µg457.16
Tiotropium + Olodaterol 2.5/5474.80
Tiotropium + Olodaterol 5/5454.08

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Forced Expiratory Volume in 1 Second (One Hour Post-dose)

"Forced Expiratory Volume in 1 Second (FEV1) (one hour post-dose)~The presented means are adjusted means from MMRM model." (NCT01533922)
Timeframe: 6 weeks

InterventionLitres (Mean)
Placebo1.497
Olodaterol 5 µg1.689
Tiotropium 5 µg1.706
Tiotropium + Olodaterol 2.5/51.783
Tiotropium + Olodaterol 5/51.820

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Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap

"Inspiratory capacity (IC) at rest before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap).~Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.~The presented means are adjusted means from the MMRM (Mixed Effects Model Repeated Measures) model." (NCT01533922)
Timeframe: 6 weeks

InterventionLitres (Mean)
Placebo2.440
Olodaterol 5 µg2.566
Tiotropium 5 µg2.571
Tiotropium + Olodaterol 2.5/52.658
Tiotropium + Olodaterol 5/52.685

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Slope of the Intensity of Breathing Discomfort (Borg Scale) During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap

"Slope of the intensity of breathing discomfort (Borg Scale) during CWRCE to symptom limitation at 75% Wcap. The intensity of breathing discomfort was rated using the modified Borg scale with ratings from 0 (nothing at all) to 10 (maximal).~Slope is defined as : (intensity of breathing discomfort at the end of exercise minus intensity of breathing discomfort at rest) / endurance time.~A decrease in slope indicates improvement.~The presented means are adjusted means from MMRM model." (NCT01533935)
Timeframe: 6 weeks

Interventionunits on a scale / s (Mean)
Placebo0.018
Olodaterol 5 µg0.017
Tiotropium 5 µg0.015
Tiotropium + Olodaterol 2.5/50.014
Tiotropium + Olodaterol 5/50.015

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Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap

"Endurance time during constant work rate cycle ergometry (CWRCE) to symptom limitation at 75% Wcap~Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.~The presented means are adjusted mean from the MMRM model." (NCT01533935)
Timeframe: 6 weeks

Interventionseconds (Geometric Mean)
Placebo410.77
Olodaterol 5 µg419.06
Tiotropium 5 µg446.50
Tiotropium + Olodaterol 2.5/5460.66
Tiotropium + Olodaterol 5/5465.68

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FEV1 (1 Hour Post-dose)

"Forced Expiratory Volume in 1 Second (FEV1) (one hour post-dose).~The presented means are adjusted means from MMRM model." (NCT01533935)
Timeframe: 6 weeks

InterventionLitres (Mean)
Placebo1.548
Olodaterol 5 µg1.742
Tiotropium 5 µg1.741
Tiotropium + Olodaterol 2.5/51.852
Tiotropium + Olodaterol 5/51.876

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Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity

"Inspiratory capacity (IC) at rest before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap).~Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.~The presented means are adjusted means from the MMRM (Mixed Effects Model Repeated Measures) model." (NCT01533935)
Timeframe: 6 weeks

InterventionLitres (Mean)
Placebo2.502
Olodaterol 5 µg2.687
Tiotropium 5 µg2.679
Tiotropium + Olodaterol 2.5/52.776
Tiotropium + Olodaterol 5/52.767

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Trough FEV1 Response

"Trough Forced Expiratory Volume in 1 second Response. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements after 52 weeks. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.~Note: The Mean presented is the unadjusted mean." (NCT01536262)
Timeframe: Baseline and 1 h, 10 min pre-dose after 52 weeks

InterventionL (Mean)
Olodaterol (5 μg)0.075
Tiotropium + Olodaterol (2.5 / 5 μg)0.168
Tiotropium + Olodaterol (5 / 5 μg)0.143

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FEV1 AUC0-3h Response

"Forced Expiratory Volume in 1 second Area Under Curve (AUC0-3h) response. FEV1 AUC0-3h was calculated using the trapezoidal rule, divided by the duration (3 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug.~Note: The Mean presented is the unadjusted mean." (NCT01536262)
Timeframe: Baseline and 1 h, 10 min pre-dose and 30 min, 1 h, 2 h, 3 h post-dose after 52 weeks

InterventionL (Mean)
Olodaterol (5 μg)0.132
Tiotropium + Olodaterol (2.5 / 5 μg)0.260
Tiotropium + Olodaterol (5 / 5 μg)0.237

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FVC AUC0-24h Response [L] After 6 Weeks Treatment.

"Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres(L) (Mean)
Placebo-0.065
Olodaterol (5 µg)0.158
Tiotropium (2.5 µg)0.172
Tiotropium (5 µg)0.191
Tiotropium+Olodaterol FDC (2.5/5 µg)0.331
Tiotropium+Olodaterol FDC (5/5 µg)0.368

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Peak(0-3h) FEV1 Response [L] After 6 Weeks Treatment.

"Peak (0-3h) Forced Expiratory Volume in 1 second (FEV1) response.~The peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo0.072
Olodaterol (5 µg)0.291
Tiotropium (2.5 µg)0.290
Tiotropium (5 µg)0.300
Tiotropium+Olodaterol FDC (2.5/5 µg)0.422
Tiotropium+Olodaterol FDC (5/5 µg)0.411

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Peak (0-3h) FVC Response [L] After 6 Weeks Treatment.

"Peak (0-3h) Forced Vital Capacity (FVC) responses after 6 weeks treatment.~Peak was defined as the maximum value measured within the first 3 h post dosing and response was defined as the change from patient baseline.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo0.159
Olodaterol (5 µg)0.463
Tiotropium (2.5 µg)0.450
Tiotropium (5 µg)0.470
Tiotropium+Olodaterol FDC (2.5/5 µg)0.612
Tiotropium+Olodaterol FDC (5/5 µg)0.621

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Trough FEV1 Response [L] After 6 Weeks Treatment.

"Trough Forced Expiratory Volume in 1 second (FEV1) response after 6 weeks treatment period.~The trough was defined as the mean of the 23 h and 23 h50 min measurements and Response was defined as the change from patient baseline.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (Mean)
Placebo-0.006
Olodaterol (5 µg)0.109
Tiotropium (2.5 µg)0.095
Tiotropium (5 µg)0.122
Tiotropium+Olodaterol FDC (2.5/5 µg)0.196
Tiotropium+Olodaterol FDC (5/5 µg)0.201

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FVC AUC12-24h Response [L] After 6 Weeks Treatment.

"Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo-0.108
Olodaterol (5 µg)0.077
Tiotropium (2.5 µg)0.095
Tiotropium (5 µg)0.122
Tiotropium+Olodaterol FDC (2.5/5 µg)0.243
Tiotropium+Olodaterol FDC (5/5 µg)0.296

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FVC AUC0-12h Response [L] After 6 Weeks Treatment.

"Area under the Forced Vital Capacity (FVC) after 6 weeks treatment period-time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo-0.023
Olodaterol (5 µg)0.240
Tiotropium (2.5 µg)0.249
Tiotropium (5 µg)0.261
Tiotropium+Olodaterol FDC (2.5/5 µg)0.420
Tiotropium+Olodaterol FDC (5/5 µg)0.440

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Forced Expiratory Volume in 1 Second (FEV1) AUC0-24h Response [L] After 6 Weeks Treatment.

"Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 24 h post-dose, using the trapezoidal rule, divided by the duration (24 h) to report in litres.~Mean is actually the Adjusted mean.~The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo-0.037
Olodaterol (5 µg)0.129
Tiotropium (2.5 µg)0.117
Tiotropium (5 µg)0.133
Tiotropium+Olodaterol FDC (2.5/5 µg)0.241
Tiotropium+Olodaterol FDC (5/5 µg)0.244

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Trough FVC Response [L] After 6 Weeks Treatment.

"Trough Forced Vital Capacity (FVC) response after 6 weeks treatment period.~The trough was defined as the mean of the 23 h and 23 h50 min measurements and response was defined as the change from patient baseline.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day1 and week 6

InterventionLitres (L) (Mean)
Placebo-0.025
Olodaterol (5 µg)0.134
Tiotropium (2.5 µg)0.115
Tiotropium (5 µg)0.183
Tiotropium+Olodaterol FDC (2.5/5 µg)0.282
Tiotropium+Olodaterol FDC (5/5 µg)0.304

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FEV1 AUC12-24h Response [L] After 6 Weeks Treatment.

"Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 12 to 24 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo-0.060
Olodaterol (5 µg)0.079
Tiotropium (2.5 µg)0.062
Tiotropium (5 µg)0.081
Tiotropium+Olodaterol FDC (2.5/5 µg)0.172
Tiotropium+Olodaterol FDC (5/5 µg)0.182

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FEV1 AUC0-12h Response [L] After 6 Weeks Treatment.

"Area under the Forced Expiratory Volume in 1 second (FEV1) after 6 weeks treatement-time curve from 0 to 12 h post-dose, using the trapezoidal rule, divided by the duration (12h) to report in litres.~Mean is actually the Adjusted mean.~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment and period; period baseline and patient baseline as covariates; patient as a random effect; compound symmetry covariance structure for within-patient variation and Kenward-Roger approximation of denominator degrees of freedom." (NCT01559116)
Timeframe: day 1 and week 6

InterventionLitres (L) (Mean)
Placebo-0.013
Olodaterol (5 µg)0.179
Tiotropium (2.5 µg)0.171
Tiotropium (5 µg)0.186
Tiotropium+Olodaterol FDC (2.5/5 µg)0.310
Tiotropium+Olodaterol FDC (5/5 µg)0.305

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Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline

Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as changes from baseline (NCT01694771)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5µg) and Tiotropium (18µg)0.389
Placebo and Tiotropium (18µg)0.270

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Rescue Medication Usage - Percentage of Rescue Free Days

Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment). (NCT01694771)
Timeframe: over 12 weeks

,
Interventionpercentage of days (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5µg) and Tiotropium (18µg)52.63354.91556.56260.58060.40557.78258.64258.93159.35059.99159.54363.353
Placebo and Tiotropium (18µg)48.60650.77450.26255.57752.61450.54750.72751.61851.39952.53550.58454.894

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Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)

Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary. (NCT01694771)
Timeframe: over 12 weeks

,
Interventionusage (total daily) number of puffs (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5µg) and Tiotropium (18µg)1.7601.7471.6991.7301.6091.6821.6571.6131.6221.5711.5331.520
Placebo and Tiotropium (18µg)2.0282.0732.0942.0572.0372.0472.0532.0422.0562.0502.0201.998

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Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)

Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary. (NCT01694771)
Timeframe: over 12 weeks

,
Interventionpercentage of days (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5µg) and Tiotropium (18µg)1.3701.3361.3091.3401.2301.2851.2651.2371.5971.1861.1771.178
Placebo and Tiotropium (18µg)1.6171.6201.6541.6401.5811.5961.6001.5871.2251.6001.5811.571

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Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)

Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary. (NCT01694771)
Timeframe: over 12 weeks

,
Interventionpercentage of days (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5µg) and Tiotropium (18µg)0.3920.4150.3940.3930.3830.4040.4020.3850.4040.3900.3600.346
Placebo and Tiotropium (18µg)0.4090.4490.4370.4160.4540.4470.4550.4510.4570.4480.4410.429

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Trough FVC Response at 12 Weeks- Defined as Change From Baseline

Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline. (NCT01694771)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5µg) and Tiotropium (18µg)0.276
Placebo and Tiotropium (18µg)0.213

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Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12

Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12 (NCT01694771)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5µg) and Tiotropium (18µg)0.195
Placebo and Tiotropium (18µg)0.133

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Peak FVC Response at 12 Weeks - Defined as Change From Baseline

Peak FVC response at 12 weeks - defined as change from baseline. (NCT01694771)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5µg) and Tiotropium (18µg)0.586
Placebo and Tiotropium (18µg)0.433

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FVC AUC0-3h Response at 12 Weeks - Defined as Change From Baseline

Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. (NCT01694771)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5µg) and Tiotropium (18µg)0.438
Placebo and Tiotropium (18µg)0.292

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FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12

FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12 (NCT01694771)
Timeframe: baseline and 12 weeks

InterventionArea Under the Curve (L) (Least Squares Mean)
Olodaterol (5µg) and Tiotropium (18µg)0.313
Placebo and Tiotropium (18µg)0.196

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FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12

FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12. AUC was standardized by dividing by time unit. (NCT01696058)
Timeframe: baseline and 12 weeks

InterventionArea Under the Curve (L) (standardized) (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)0.297
Placebo and Tiotropium (18μg)0.191

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Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)

"Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol metered dose inhaler (MDI) (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.~Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.~Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)" (NCT01696058)
Timeframe: over 12 weeks

,
Interventionusage (total daily) number of puffs (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5μg) and Tiotropium (18μg)1.6271.6521.6351.6471.5511.5231.5401.5861.5191.4991.4841.535
Placebo and Tiotropium (18μg)2.0722.1452.1672.1892.1832.1792.1382.1072.1212.1032.1072.103

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Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline

Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as change from baseline. All p-values for these measures are only descriptive. (NCT01696058)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)0.371
Placebo and Tiotropium (18μg)0.271

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Peak FVC Response at 12 Weeks; Defined as Change From Baseline

Peak FVC response at 12 weeks - defined as change from baseline. (NCT01696058)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)0.562
Placebo and Tiotropium (18μg)0.457

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Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data

The Saint George Respiratory Questionnaire (SGRQ) is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It is divided into two parts. Part I produces the Symptoms score (several scales), and Part II the Activity and Impacts scores [dichotomous (true/false) except last question (4-point Likert scale)]. A Total score is also produced with scores ranging from 0 to 100, with higher scores indicating more limitations. Since the SGRQ analysis is based on the combined data from both this study and protocol 1222.51 (NCT01694771), only combined SGRQ results will be included in the latest clinical trial report. Hence there will only be one SGRQ analysis from both studies, which will not appear in the first clinical trial report. For this same reason, another covariate - study - will also be included in the MMRM for SGRQ analysis. The combined data for this outcome measure was pre-specified in both protocols. (NCT01696058)
Timeframe: 12 weeks

Interventionunits on a scale (total score) (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)41.204
Placebo and Tiotropium (18μg)43.059

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Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12

Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12 (NCT01696058)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)0.175
Placebo and Tiotropium (18μg)0.135

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Trough FVC Response at 12 Weeks; Defined as Change From Baseline

Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline. (NCT01696058)
Timeframe: baseline and 12 weeks

InterventionL (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)0.269
Placebo and Tiotropium (18μg)0.235

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Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)

"Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.~Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.~Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)" (NCT01696058)
Timeframe: over 12 weeks

,
Interventionnumber of puffs (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5μg) and Tiotropium (18μg)0.4060.4210.4070.4080.3750.3780.4030.4170.3960.3920.3830.393
Placebo and Tiotropium (18μg)0.4370.4660.4590.4790.4790.4910.4990.4820.4870.4800.4820.483

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Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)

"Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.~Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.~Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)" (NCT01696058)
Timeframe: over 12 weeks

,
Interventionnumber of puffs (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5μg) and Tiotropium (18μg)1.2221.2321.2291.2391.1771.1481.1391.1731.1251.1081.1041.143
Placebo and Tiotropium (18μg)1.6331.6771.7071.7091.7101.6921.6411.6281.6361.6301.6301.625

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Rescue Medication Usage - Percentage of Rescue Free Days

"Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment).~Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.~Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552)" (NCT01696058)
Timeframe: over 12 weeks

,
Interventionpercentage of days (Least Squares Mean)
Week 1Week 2Week 3Week 4Week 5Week 6Week 7Week 8Week 9Week 10Week 11Week 12
Olodaterol (5μg) and Tiotropium (18μg)53.20754.24954.82060.76160.15459.70759.49359.02160.52460.21659.65062.327
Placebo and Tiotropium (18μg)48.58348.64049.86555.96951.84049.00150.16451.01751.27351.63451.60455.090

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FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline

Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit. (NCT01696058)
Timeframe: baseline and 12 Weeks

InterventionL (Least Squares Mean)
Olodaterol (5μg) and Tiotropium (18μg)0.424
Placebo and Tiotropium (18μg)0.306

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CLR,t1-t2,ss (Tiotropium)

"Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.~Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg)." (NCT01703845)
Timeframe: from 0 to 4 hours following drug administration on day 21

InterventionmL/min (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)292

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Aet1-t2,ss (Olodaterol)

"Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: from 0 to 4 hours following drug administration on day 21

Interventionnanogram (ng) (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)74.8
Tiotropium + Olodaterol (2.5µg/5µg)50.0

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AUC0-tz,ss (Olodaterol)

"Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

Interventionpg*h/mL (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)9.94
Tiotropium + Olodaterol (2.5µg/5µg)6.85

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AUC0-tz,ss (Tiotropium)

"Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

Interventionpg*h/mL (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)23.3
Tiotropium + Olodaterol (2.5µg/5µg)7.99

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AUCt1-t2,ss (Olodaterol)

"Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21

Interventionpg*h/mL (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)9.94
Tiotropium + Olodaterol (2.5µg/5µg)8.14

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AUCt1-t2,ss (Tiotropium)

"Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21

Interventionpg*h/mL (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)14.8
Tiotropium + Olodaterol (2.5µg/5µg)7.00

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CLR,t1-t2,ss (Olodaterol)

"Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: from 0 to 4 hours following drug administration on day 21

InterventionmL/min (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)152
Tiotropium + Olodaterol (2.5µg/5µg)148

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Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG

"Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.~There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG." (NCT01703845)
Timeframe: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose

,
Interventionparticipants (Number)
AEs reported related to vital signsAEs reported related to ECGHaematuriaBlood creatine phosphokinase increasedBlood urine present
Tiotropium + Olodaterol (2.5µg/5µg)00100
Tiotropium + Olodaterol (5µg/5µg)00011

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Cmax,ss (Olodaterol)

"Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21

Interventionpicogram/milliliter (pg/mL) (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)4.33
Tiotropium + Olodaterol (2.5µg/5µg)2.82

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fe t1-t2,ss (Olodaterol)

"Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: from 0 to 4 hours following drug administration on day 21

Interventionpercentage of dose (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)1.50
Tiotropium + Olodaterol (2.5µg/5µg)0.999

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fe t1-t2,ss (Tiotropium)

"Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: from 0 to 4 hours following drug administration on day 21

Interventionpercentage of dose (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)6.72
Tiotropium + Olodaterol (2.5µg/5µg)4.89

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Cmax,ss (Tiotropium)

"Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21

Interventionpicogram/milliliter (pg/mL) (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)16.5
Tiotropium + Olodaterol (2.5µg/5µg)6.49

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Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)

Outcome data show are the number of patients with an adverse event including the assessment based on physical examination. (NCT01703845)
Timeframe: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose

Interventionparticipants (Number)
Tiotropium + Olodaterol (5µg/5µg)4
Tiotropium + Olodaterol (2.5µg/5µg)2

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Tmax,ss (Olodaterol)

"Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21

Interventionh (Median)
Tiotropium + Olodaterol (5µg/5µg)0.183
Tiotropium + Olodaterol (2.5µg/5µg)0.217

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Tmax,ss (Tiotropium)

"Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21

Interventionh (Median)
Tiotropium + Olodaterol (5µg/5µg)0.100
Tiotropium + Olodaterol (2.5µg/5µg)0.100

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Aet1-t2,ss (Tiotropium)

"Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).~Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type." (NCT01703845)
Timeframe: from 0 to 4 hours following drug administration on day 21

Interventionnanogram (ng) (Geometric Mean)
Tiotropium + Olodaterol (5µg/5µg)336
Tiotropium + Olodaterol (2.5µg/5µg)122

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FVC AUC0-3h Response (Change From Baseline)

The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT01964352)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo-0.011
Tiotropium 5 μg0.286
Tiotropium 2.5 μg+ Olodaterol 5 μg0.387
Tiotropium 5 μg + Olodaterol 5 μg0.446

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FEV1 AUC0-3h Response

Forced expiratory volume in one second (FEV1) Area under the curve (AUC) 0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in litres. FEV1 AUC0-3h response was defined as FEV1 AUC0-3h minus baseline FEV1. The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT01964352)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo-0.014
Tiotropium 5 μg0.205
Tiotropium 2.5 μg+ Olodaterol 5 μg0.285
Tiotropium 5 μg + Olodaterol 5 μg0.316

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TDI Focal Score

"This endpoint was evaluated based on the data from this individual trial and also based on the data from the combined dataset from this trial and the replicate study NCT02006732. The results for the combined dataset are included in the disclosure for NCT02006732 as specified in the analysis plan. Mahler Transitional Dyspnoea Index (TDI) focal score was performed to measure the effect of the treatment on patients' dyspnoea.(Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9).~The adjusted mean (SE) are obtained from fitting an MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom." (NCT01964352)
Timeframe: 12 weeks

InterventionUnits on a scale (Mean)
Placebo-0.113
Tiotropium 5 μg1.332
Tiotropium 2.5 μg+ Olodaterol 5 μg1.839
Tiotropium 5 μg + Olodaterol 5 μg1.939

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Trough FEV1 Response (Change From Baseline)

Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FEV1 measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FEV1 response was defines as trough FEV1 minus baseline FEV1. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT01964352)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo0.001
Tiotropium 5 μg0.135
Tiotropium 2.5 μg+ Olodaterol 5 μg0.151
Tiotropium 5 μg + Olodaterol 5 μg0.163

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Trough Forced Vital Capacity (FVC) Response (Change From Baseline)

Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FVC measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FVC response was defined as trough FVC minus baseline FVC. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT01964352)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo0.025
Tiotropium 5 μg0.223
Tiotropium 2.5 μg+ Olodaterol 5 μg0.233
Tiotropium 5 μg + Olodaterol 5 μg0.244

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St. George's Respiratory Questionnaire (SGRQ) Total Score

"This endpoint was evaluated based on the data from this individual trial and also based on the data from the combined dataset from this trial and the replicate study NCT02006732. The results for the combined dataset are included in the disclosure for NCT02006732 as specified in the analysis plan. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life).~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom." (NCT01964352)
Timeframe: 12 weeks treatment

Interventionunits on a scale (Mean)
Placebo42.038
Tiotropium 5 μg39.637
Tiotropium 2.5 μg+ Olodaterol 5 μg37.916
Tiotropium 5 μg + Olodaterol 5 μg37.144

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Trough FEV1 Change From Patient Baseline After 6 Weeks of Treatment

"Change from patient baseline in Trough Forced Expiratory Volume in one second (FEV1) after 6 weeks of treatment. Trough FEV1 was defined as the mean of the 23h and 23h 50min (minutes) post-dose FEV1 measurements. Measured values presented are actually adjusted means.~The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient." (NCT01969721)
Timeframe: Baseline and 6 weeks.

InterventionLitres (Mean)
T+O 2.5/5 / F+S Placebo0.192
T+O 5/5 / F+S Placebo0.197
F+S 250/50 / T+O Placebo0.150
F+S 500/50 / T+O Placebo0.139

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FEV1 AUC (0-12h) Change From Patient Baseline After 6 Weeks of Treatment

"Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 12hours post-dose (AUC 0-12h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means.~The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient." (NCT01969721)
Timeframe: Baseline and 6 weeks.

InterventionLitres (Mean)
T+O 2.5/5 / F+S Placebo0.295
T+O 5/5 / F+S Placebo0.317
F+S 250/50 / T+O Placebo0.192
F+S 500/50 / T+O Placebo0.188

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FEV1 AUC (0-24h) Change From Patient Baseline After 6 Weeks of Treatment

"Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 0 to 24 hours post-dose (AUC 0-24h) [L] after 6 weeks of treatment.~Measured values presented are actually adjusted means. The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient." (NCT01969721)
Timeframe: Baseline and 6 weeks.

InterventionLitres (Mean)
T+O 2.5/5 / F+S Placebo0.228
T+O 5/5 / F+S Placebo0.244
F+S 250/50 / T+O Placebo0.162
F+S 500/50 / T+O Placebo0.159

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FEV1 AUC (12-24h) Change From Patient Baseline After 6 Weeks of Treatment

"Change from patient baseline in Forced Expiratory Volume in one second (FEV1) Area Under the FEV1-time Curve from 12 to 24 hours post-dose (AUC 12-24h) [L] after 6 weeks of treatment. Measured values presented are actually adjusted means.~The period baseline is defined as the pre-dose measurement taken at on the day 1 of each period. The patient baseline is defined as the mean of non-missing period baselines for each patient." (NCT01969721)
Timeframe: Baseline and 6 weeks.

InterventionLitres (Mean)
T+O 2.5/5 / F+S Placebo0.160
T+O 5/5 / F+S Placebo0.172
F+S 250/50 / T+O Placebo0.132
F+S 500/50 / T+O Placebo0.129

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FEV1 Peak (0-3h) Change From Patient Baseline After 6 Weeks of Treatment

Change from patient baseline in Forced Expiratory Volume in one second (FEV1) peak (0-3 hours) after 6 weeks of treatment. FEV1 peak (0-3 hours) was defined as the maximum FEV1 value measured within the first three hours post dosing. Measured values presented are actually adjusted means. (NCT01969721)
Timeframe: Baseline and 6 weeks.

InterventionLitres (Mean)
T+O 2.5/5 / F+S Placebo0.401
T+O 5/5 / F+S Placebo0.432
F+S 250/50 / T+O Placebo0.291
F+S 500/50 / T+O Placebo0.285

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St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Combined Dataset From This Study and the Replicate Study NCT01964352

"This endpoint was evaluated after combining the data from this and the replicate study NCT01964352 as specified in the analysis plan. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life).~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom." (NCT02006732)
Timeframe: 12 weeks treatment

Interventionunits on a scale (Mean)
Placebo42.265
Tiotropium 5 μg39.694
Tiotropium 2.5 μg+ Olodaterol 5 μg38.419
Tiotropium 5 μg + Olodaterol 5 μg37.597

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TDI Focal Score Based on Combined Dataset From This Study and the Replicate Study NCT01964352

"This endpoint was evaluated after combining the data from this and the replicate study NCT01964352 as specified in the analysis plan. Mahler Transitional Dyspnoea Index (TDI) focal score was performed to measure the effect of the treatment on patients' dyspnoea.(Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9).~The adjusted mean (SE) are obtained from fitting an MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom." (NCT02006732)
Timeframe: 12 weeks

InterventionUnits on a scale (Mean)
Placebo0.111
Tiotropium 5 μg1.140
Tiotropium 2.5 μg+ Olodaterol 5 μg1.722
Tiotropium 5 μg + Olodaterol 5 μg1.734

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St. George's Respiratory Questionnaire (SGRQ) Total Score Based on Data From This Individual Study

"The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life).~The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom." (NCT02006732)
Timeframe: 12 weeks treatment

Interventionunits on a scale (Mean)
Placebo42.575
Tiotropium 5 μg39.729
Tiotropium 2.5 μg+ Olodaterol 5 μg38.909
Tiotropium 5 μg + Olodaterol 5 μg38.011

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FVC AUC0-3h Response (Change From Baseline)

The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT02006732)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo-0.018
Tiotropium 5 μg0.266
Tiotropium 2.5 μg+ Olodaterol 5 μg0.436
Tiotropium 5 μg + Olodaterol 5 μg0.414

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FEV1 AUC0-3h Response

Forced expiratory volume in one second (FEV1) Area under the curve (AUC) 0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in litres. FEV1 AUC0-3h response was defined as FEV1 AUC0-3h minus baseline FEV1. The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT02006732)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo-0.006
Tiotropium 5 μg0.188
Tiotropium 2.5 μg+ Olodaterol 5 μg0.279
Tiotropium 5 μg + Olodaterol 5 μg0.293

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TDI Focal Score Based on Data From This Individual Study

"Mahler Transitional Dyspnoea Index (TDI) focal score was performed to measure the effect of the treatment on patients' dyspnoea.(Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9).~The adjusted mean (SE) are obtained from fitting an MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom." (NCT02006732)
Timeframe: 12 weeks

InterventionUnits on a scale (Mean)
Placebo0.337
Tiotropium 5 μg0.950
Tiotropium 2.5 μg+ Olodaterol 5 μg1.599
Tiotropium 5 μg + Olodaterol 5 μg1.531

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Trough FEV1 Response (Change From Baseline)

Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FEV1 measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FEV1 response was defines as trough FEV1 minus baseline FEV1. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT02006732)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo-0.003
Tiotropium 5 μg0.124
Tiotropium 2.5 μg+ Olodaterol 5 μg0.166
Tiotropium 5 μg + Olodaterol 5 μg0.163

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Trough Forced Vital Capacity (FVC) Response (Change From Baseline)

Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FVC measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FVC response was defined as trough FVC minus baseline FVC. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom. (NCT02006732)
Timeframe: baseline and 12 weeks

InterventionL (Mean)
Placebo-0.021
Tiotropium 5 μg0.170
Tiotropium 2.5 μg+ Olodaterol 5 μg0.284
Tiotropium 5 μg + Olodaterol 5 μg0.231

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QRS Change From Patient Baseline at Individual Post-dose Time Points

QRS change from patient baseline at individual post-dose time points (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

,,
Interventionms (Mean)
5 min10 min25 min50 min
Placebo-0.3-0.3-0.3-0.4
Tio+Olo 5/5μg-0.20.10.10.2
Tiotropium 5μg + Olodaterol 5μg-0.00.10.00.2

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QT Change From Patient Baseline at Individual Post-dose Time Points

QT change from patient baseline at individual post-dose time points (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

,,
Interventionms (Mean)
5 min10 min25 min50 min
Placebo4.37.17.99.4
Tio+Olo 5/5μg5.56.37.46.7
Tiotropium 5μg + Olodaterol 5μg4.97.99.69.4

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QTcB Change From Patient Baseline at Individual Post-dose Time Points

QTcB change from patient baseline at individual post-dose time points (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

,,
Interventionms (Mean)
5 min10 min25 min50 min
Placebo-2.5-1.4-1.0-2.6
Tio+Olo 5/5μg-1.4-0.20.10.7
Tiotropium 5μg + Olodaterol 5μg-2.6-0.0-2.2-0.7

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RR Change From Patient Baseline at Individual Post-dose Time Points

RR change from patient baseline at individual post-dose time points (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

,,
Interventionms (Mean)
5 min10 min25 min50 min
Placebo29.938.840.452.3
Tio+Olo 5/5μg29.728.133.025.2
Tiotropium 5μg + Olodaterol 5μg31.933.550.044.0

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Peak PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Peak PR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo3.9
Tio+Olo 5/5μg4.6
Tiotropium 5μg + Olodaterol 5μg4.7

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Peak Heart Rate Change From Patient Baseline Over All Post-dose Time Points

Peak heart rate change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionbpm (Mean)
Placebo-0.7
Tio+Olo 5/5μg-0.3
Tiotropium 5μg + Olodaterol 5μg-1.2

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Mean RR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean RR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo40.4
Tio+Olo 5/5μg29.3
Tiotropium 5μg + Olodaterol 5μg39.5

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Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points

Peak QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment))change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo3.0
Tio+Olo 5/5μg4.2
Tiotropium 5μg + Olodaterol 5μg3.5

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Mean QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean QT change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo7.2
Tio+Olo 5/5μg6.5
Tiotropium 5μg + Olodaterol 5μg7.9

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Mean QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean QRS change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo-0.3
Tio+Olo 5/5μg0.1
Tiotropium 5μg + Olodaterol 5μg0.1

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Mean PR (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Mean PR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo0.6
Tio+Olo 5/5μg1.6
Tiotropium 5μg + Olodaterol 5μg1.4

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Mean Heart Rate Change From Patient Baseline Over All Post-dose Time Points

Mean heart rate change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionbpm (Mean)
Placebo-3.0
Tio+Olo 5/5μg-2.5
Tiotropium 5μg + Olodaterol 5μg-3.6

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Peak QTcF Interval Change From Patient Baseline Over All Post-dose Time Points

Peak QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo5.2
Tio+Olo 5/5μg5.7
Tiotropium 5μg + Olodaterol 5μg5.7

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Peak RR Change From Patient Baseline Over All Post-dose Time Points

Peak RR change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo68.8
Tio+Olo 5/5μg55.5
Tiotropium 5μg + Olodaterol 5μg68.0

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Mean (Heart Rate Corrected QT Interval (Using Fredericia Adjustment)) QTcF Interval Change From Patient Baseline Over All Post-dose Time Points

Mean QTcF interval change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo1.3
Tio+Olo 5/5μg2.2
Tiotropium 5μg + Olodaterol 5μg1.9

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Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3hours) Response After Single-dose Administration

"The response was defined as the change from patient baseline. Patient baseline was the average of the mean pre-dose values (period baseline) on each test day (Visit 2 (Day 1), Visit 3 (Day 22 (±7days)), and Visit 4 (Day 43±7days)).~For patients who did not complete all periods, patient baseline was the average of the available period baselines.~The means presented are the adjusted means." (NCT02030535)
Timeframe: 1 hour (h) and 10 min pre-dose and at 15 min, 30 min, 1 h, 2 h and 3 h post-dose

InterventionLitres (Mean)
Placebo0.014
Tio+Olo 5/5μg0.233
Tiotropium 5μg + Olodaterol 5μg0.266

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Peak QRS (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Peak QRS change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo0.6
Tio+Olo 5/5μg0.9
Tiotropium 5μg + Olodaterol 5μg1.0

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Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment)) Change From Patient Baseline Over All Post-dose Time Points

Mean QTcB (Heart Rate Corrected QT Interval (Using Bazett Adjustment))change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo-1.9
Tio+Olo 5/5μg-0.2
Tiotropium 5μg + Olodaterol 5μg-1.4

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Heart Rate Change From Patient Baseline at Individual Post-dose Time Points

Heart rate change from patient baseline at individual post-dose time points (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

,,
Interventionbpm (Mean)
5 min10 min25 min50 min
Placebo-2.3-2.7-3.1-4.1
Tio+Olo 5/5μg-2.5-2.4-2.6-2.4
Tiotropium 5μg + Olodaterol 5μg-2.9-3.1-4.5-3.9

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PR Change From Patient Baseline at Individual Post-dose Time Points

PR change from patient baseline at individual post-dose time points (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

,,
Interventionms (Mean)
5 min10 min25 min50 min
Placebo0.10.10.12.2
Tio+Olo 5/5μg1.22.50.81.9
Tiotropium 5μg + Olodaterol 5μg-0.21.41.92.7

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Peak QT (Time Interval of ECG) Change From Patient Baseline Over All Post-dose Time Points

Peak QT change from patient baseline over all post-dose time points (5min, 10min, 25min and 50min) (NCT02030535)
Timeframe: 40 min pre-dose and at 5 min, 10 min, 25 min and 50 min post-dose

Interventionms (Mean)
Placebo12.4
Tio+Olo 5/5μg11.5
Tiotropium 5μg + Olodaterol 5μg13.4

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Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks

Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of predicted maximum oxygen consumption (VO2 peak) after 8 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then an analysis of covariance (ANCOVA) was fitted to the log10-transformed data and the least square means (LSMean) and standard error (SE) were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean. (NCT02085161)
Timeframe: Week 8

InterventionSecond (Geometric Mean)
Placebo With Behavioural Modification (BM)244.07
Tiotropium (Tio) 5 Micro-grams (μg) With BM254.18
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM315.32
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM355.73

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One Hour, Post-dose Forced Expiratory Volume in One Second (FEV1) After 8 Weeks of Treatment

One hour, Post-dose Forced Expiratory Volume in One Second (FEV1) after 8 weeks of treatment. (NCT02085161)
Timeframe: Week 8

InterventionLiter (Least Squares Mean)
Placebo With Behavioural Modification (BM)1.375
Tiotropium (Tio) 5 Micro-grams (μg) With BM1.550
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM1.731
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM1.705

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One Hour, Post-dose Forced Vital Capacity (FVC) After 8 Weeks of Treatment

One hour, Post-dose Forced Vital Capacity (FVC) after 8 weeks of treatment. (NCT02085161)
Timeframe: Week 8

InterventionLiter (Least Squares Mean)
Placebo With Behavioural Modification (BM)2.974
Tiotropium (Tio) 5 Micro-grams (μg) With BM3.259
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM3.504
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM3.452

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Perceived Difficulties as Evaluated With Functional Performance Inventory-Short Form (FPI-SF) Total Score at Week 12

Perceived difficulties as evaluated with FPI-SF. FPI-SF self-report questionnaire has 6 domains: Body care(5 items), Household maintenance(8 items), Physical exercise(5 items), Recreation(5 items), Spiritual activities(4 items) and Social interaction(5 items) with five possible answers on each item: Do with no difficulty - 3, Do with some difficulty - 2, Do with great difficulty - 1, don't do because of health reasons - 0, and don't do because choose not to - 0. Domain scores are expressed as mean values, with at least 6 non-missing items required for the household maintenance domain and at least 3 non-missing items for the other domains. Total score is the mean across the six domains. So total and domain scores range from 0 to 3, with higher scores indicating higher levels of functional activity within and across domains. Respondents engaged in many activities with no difficulty will score high on the FPI, while those who perform few activities with much difficulty will score low. (NCT02085161)
Timeframe: Week 12

InterventionUnits on a scale (Least Squares Mean)
Placebo With Behavioural Modification (BM)2.191
Tiotropium (Tio) 5 Micro-grams (μg) With BM2.207
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM2.335
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM2.268

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Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12

Average daily walking time measured by the activity monitor in the week prior to Week 12. (NCT02085161)
Timeframe: Week 12

InterventionSecond (Least Squares Mean)
Placebo With Behavioural Modification (BM)4670.78
Tiotropium (Tio) 5 Micro-grams (μg) With BM4145.85
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM4831.85
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM4338.80

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Resting Inspiratory Capacity (IC) Measured at 1.5 Hours Post Dose After 8 Weeks of Treatment

Resting inspiratory capacity (IC) measured at 1.5 hours post dose after 8 weeks of treatment. (NCT02085161)
Timeframe: Week 8

InterventionLiter (Least Squares Mean)
Placebo With Behavioural Modification (BM)2.452
Tiotropium (Tio) 5 Micro-grams (μg) With BM2.627
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM2.755
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM2.771

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Average Daily Walking Intensity Measured by the Activity Monitor in the Week Prior to 12 Weeks of Treatment

Average daily walking intensity measured by the activity monitor in the week prior to 12 weeks of treatment. The Movement Intensity (MI) is derived from the acceleration signals. Since seismic sensors measure gravitational acceleration (g) in static situations, the acceleration signal is expressed relative to g (1g = 9.81m/s2). To calculate movement intensity (MI) the gravitational acceleration in static situations was removed and the rotation vector of the three accelerometer signals was calculated. The MI gives an indication of the power of movements. (NCT02085161)
Timeframe: Week 12

InterventionMultiple of 9.8*(meters / (second^2)) (Least Squares Mean)
Placebo With Behavioural Modification (BM)0.20
Tiotropium (Tio) 5 Micro-grams (μg) With BM0.20
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM0.20
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM0.20

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Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 12 Weeks

Endurance time during ESWT to symptom limitation at walking speed corresponding to 85% of maximum oxygen consumption (VO2 peak) after 12 weeks of pharmacological treatment and non-pharmacological intervention. The numerical value of endurance time in seconds was transformed in log10 scale to correct for skewness and then the ANCOVA was fitted to the log10-transformed data and the least square means and SE were obtained. To present the results in a way easier for interpretation, the least square mean from the ANCOVA fitted to the log10-transformed data were transformed back taking 10 to the power of the least square estimate to obtain the geometric mean and the corresponding SE was transformed using delta method to get the corresponding SE of the geometric mean. (NCT02085161)
Timeframe: Week 12

InterventionSecond (Geometric Mean)
Placebo With Behavioural Modification (BM)243.30
Tiotropium (Tio) 5 Micro-grams (μg) With BM255.67
Tiotropium + Olodaterol (Olo) (5/5 μg) FDC With BM302.61
Tio+Olo (5/5 μg) FDC With Exercise Training (ET) and BM324.21

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General Health of the Patient After 4-6 Weeks

"General health of the patient as evaluated by the physician using the Physician´s Global Evaluation (PGE) score after 4-6 weeks.~The PGE score consists of an 8-point-scale which extends from 1 (very bad) to 8 (excellent)." (NCT02173769)
Timeframe: 4-6 weeks

InterventionPercentage of participants (Number)
1 (poor)2345678 (excellent)
All Patients0.965.4813.6722.6025.0822.098.251.86

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General Health of the Patient at Baseline

"General health of the patient as evaluated by the physician using the Physician´s Global Evaluation (PGE) score at the initial examination.~The PGE score consists of an 8-point-scale which extends from 1 (very bad) to 8 (excellent)." (NCT02173769)
Timeframe: Baseline

InterventionPercentage of participants (Number)
1 (poor)2345678 (excellent)
All Patients2.1014.7225.7329.1316.579.442.160.11

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Patient Satisfaction: Overall Satisfaction

"Patient satisfaction with Spiriva Respimat plus Striverdi Respimat or Spiriva 18 Microgram plus Striverdi Respimat.~Patient´s satisfaction with study treatment and handling of the Respimat inhaler was assessed on a 7-point-ordinal scale extending from very satisfied (1) to very unsatisfied (7)." (NCT02173769)
Timeframe: 4-6 weeks

InterventionPercentage of participants (Number)
Very satisifedSatisfiedRather satisfiedNeither satisfied or dissatisfiedRather dissatisfiedDissatisfiedVery dissatisfied
All Patients25.2142.1313.539.704.294.061.07

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Patient Satisfaction: Satisfaction With Handling of Inhaler

"Patient satisfaction with Spiriva Respimat plus Striverdi Respimat or Spiriva 18 Microgram plus Striverdi Respimat.~Patient´s satisfaction with study treatment and handling of the Respimat inhaler was assessed on a 7-point-ordinal scale extending from very satisfied (1) to very unsatisfied (7)." (NCT02173769)
Timeframe: 4-6 weeks

InterventionPercentage of participants (Number)
Very satisifedSatisfiedRather satisfiedNeither satisfied or dissatisfiedRather dissatisfiedDissatisfiedVery dissatisfied
All Patients31.4449.3211.255.061.570.960.39

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Patient Satisfaction: Satisfaction With Inhaler

"Patient satisfaction with Spiriva Respimat plus Striverdi Respimat or Spiriva 18 Microgram plus Striverdi Respimat.~Patient´s satisfaction with study treatment and handling of the Respimat inhaler was assessed on a 7-point-ordinal scale extending from very satisfied (1) to very unsatisfied (7)." (NCT02173769)
Timeframe: 4-6 weeks

InterventionPercentage of participants (Number)
Very satisifedSatisfiedRather satisfiedNeither satisfied or dissatisfiedRather dissatisfiedDissatisfiedVery dissatisfied
All Patients31.5349.8610.065.121.521.460.45

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"Percentage of Participants With Therapeutic Success"

"Percentage of participants with therapeutic success defined as a 10-point increase in the physical activity assessed by patient´s questionnaire (PF-10) score between the initial examination and after 4-6 weeks.~The PF-10 score is a subscale of the quality of life questionnaire Short Form 36 (SF-36) and contains 10 questions concerning physical activity and capacity. The total score ranges from 0 to 100. A higher score indicates a better physical functioning." (NCT02173769)
Timeframe: Baseline and 4-6 weeks

InterventionPercentage of participants (Number)
Therapy successfulTherapy not successful
All Patients48.9051.10

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Absolute Changes in the PF-10 Score

"Absolute changes in the PF-10 score.~The PF-10 score is a subscale of the quality of life questionnaire Short Form 36 (SF-36) and contains 10 questions concerning physical activity and capacity. The total score ranges from 0 to 100. A higher score indicates a better physical functioning." (NCT02173769)
Timeframe: 4-6 weeks

InterventionUnits on a scale (Mean)
All Patients10.15

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Ae(0-24h,ss) of Olodaterol

"Amount of Olodaterol that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.

Interventionng (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg360.98
Olodaterol 10 µg344.17

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AUC(0-1h,ss) of Olodaterol

"Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)).~As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint.~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg4.67
Olodaterol 10 µg4.15

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AUC(0-2h,ss) of Olodaterol

"Area under the concentration time curve of Olodaterol in plasma over the time interval 0 to 2 hours at steady state (AUC(0-2h,ss)).~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg8.52
Olodaterol 10 µg8.36

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AUC(0-4h,ss) of Tiotropium

"Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=4 h at steady state (AUC(0-4h,ss)).~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg21.92
Tiotropium 5 µg24.00

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AUC(0-tz,ss) of Olodaterol

"Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Olodaterol.~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg12.20
Olodaterol 10 µg9.25

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Tmax,ss of Tiotropium

Time from dosing to the maximum concentration of Tiotropium in plasma at steady state (tmax,ss). (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionh (Median)
Tiotropium+Olodaterol 5/10 μg0.083
Tiotropium 5 µg0.083

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Cmax,ss of Olodaterol

"Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss).~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg5.87
Olodaterol 10 µg5.28

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AUC(0-6h,ss) of Tiotropium

"Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=6 h at steady state (AUC(0-6h,ss)).~As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Tiotropium. Based on the given definition AUC(0-6h,ss) was selected as secondary endpoint.~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg29.97
Tiotropium 5 µg33.24

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Cmax,ss of Tiotropium

"Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss).~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg15.55
Tiotropium 5 µg16.15

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Cmin,ss of Olodaterol

"Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).~The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg2.30
Olodaterol 10 µg2.26

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Cmin,ss of Tiotropium

"Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).~The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg2.95
Tiotropium 5 µg2.89

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fe(0-24,ss) of Olodaterol

"Fraction of Olodaterol eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).~The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpercentage of olodaterol dose (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg3.62
Olodaterol 10 µg3.57

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Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG

Clinically relevant abnormalities in vital signs (blood pressure and pulse rate), physical examination, blood chemistry, haematology, urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Any adverse events which occurred within 14 days following the last drug administration were assigned to the last study treatment administered. (NCT02231177)
Timeframe: From drug administration until 14 days following the last drug administration

Interventionparticipants (Number)
Tiotropium+Olodaterol 5/10 μg0
Olodaterol 10 µg0
Tiotropium 5 µg0

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fe(0-24,ss) of Tiotropium

"Fraction of Tiotropium eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).~The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpercentage of tiotropium dose (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg18.2
Tiotropium 5 µg18.6

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Tmax,ss of Olodaterol

Time from dosing to the maximum concentration of Olodaterol in plasma at steady state (tmax,ss). (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionh (Median)
Tiotropium+Olodaterol 5/10 μg0.25
Olodaterol 10 µg0.25

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AUC(0-tz,ss) of Tiotropium

"Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Tiotropium.~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionpg*h/mL (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg32.67
Tiotropium 5 µg32.91

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FVC Change From Baseline

"Mean change from baseline in forced vital capacity (FVC). Pulmonary function test.~The baseline value was measured pre-dose on day 1 of the first treatment period." (NCT02231177)
Timeframe: 0:30 and 1:00 h after drug administration on the first day of each treatment period

,,
InterventionL (Mean)
0:30 h after drug administration (N=47, 47, 47)1:00 h after drug administration (N=47, 46, 47)
Olodaterol 10 µg0.4500.522
Tiotropium 5 µg0.4360.470
Tiotropium+Olodaterol 5/10 μg0.4850.547

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FEV1 Change From Baseline

"Mean change from baseline in forced expiratory volume in one second (FEV1). Pulmonary function test.~The baseline value was measured pre-dose on day 1 of the first treatment period." (NCT02231177)
Timeframe: 0:30 and 1:00 h after drug administration on the first day of each treatment period

,,
InterventionL (Mean)
0:30 h after drug administration (N=47, 47, 47)1:00 h after drug administration (N=47, 46, 47)
Olodaterol 10 µg0.2920.357
Tiotropium 5 µg0.2710.284
Tiotropium+Olodaterol 5/10 μg0.2750.335

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Ae(0-24h,ss) of Tiotropium

"Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).~The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA)." (NCT02231177)
Timeframe: Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.

Interventionng (Geometric Mean)
Tiotropium+Olodaterol 5/10 μg900.57
Tiotropium 5 µg918.63

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Tmin,ss of Tiotropium

Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss) (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionh (Median)
Tiotropium+Olodaterol 5/10 μg6.00
Tiotropium 5 µg8.00

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Tmin,ss of Olodaterol

Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss) (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

Interventionh (Median)
Tiotropium+Olodaterol 5/10 μg2.00
Olodaterol 10 µg1.01

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Concentration of Olodaterol in Plasma

"Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.~The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

,
Interventionpg/mL (Geometric Mean)
C(0.333_8) (N=38, 34)C(0.333_14,ss) (N=41, 38)C(0.333_21,ss) (N=43, 40)
Olodaterol 10 µg4.484.664.80
Tiotropium+Olodaterol 5/10 μg5.095.135.23

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Concentration of Tiotropium in Plasma

"Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.~The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics." (NCT02231177)
Timeframe: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.

,
Interventionpg/mL (Geometric Mean)
C(0.333_8) (N=40, 38)C(0.333_14,ss) (N=43, 40)C(0.333_21,ss) (N=46, 44)
Tiotropium 5 µg9.589.029.21
Tiotropium+Olodaterol 5/10 μg8.909.088.34

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Annualised Rate of Exacerbations Leading to Hospitalisation During the Actual Treatment Period.

Annualised rate of exacerbations leading to hospitalisation during the actual treatment period was calculated per treatment per patient-year. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. (NCT02296138)
Timeframe: From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days

InterventionRate per patient-year (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.20
Tiotropium (5 μg) + Olodaterol (5 μg)0.18

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Annualised Rate of Moderate to Severe COPD Exacerbations During the Actual Treatment Period.

Annualised rate of moderate to severe COPD exacerbations during the actual treatment period was calculated per treatment per patient-year. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. Least Squares Means are actually exponentiated. (NCT02296138)
Timeframe: From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days

InterventionRate per patient-year (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.97
Tiotropium (5 μg) + Olodaterol (5 μg)0.90

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Number of Patients With All-cause Mortality Occurring During the Actual Treatment Period.

Number of patients with all-cause mortality occurring during the actual treatment period per treatment. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. The median was not estimated due to less than 50% of patients having an event. Hence the number of patients with all-cause mortality is presented. (NCT02296138)
Timeframe: From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days

InterventionNumber of patients (Number)
Tiotropium 5 Microgram (μg)32
Tiotropium (5 μg) + Olodaterol (5 μg)36

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Number of Patients With at Least One COPD Exacerbation Leading to Hospitalisation During the Actual Treatment Period.

Number of patients with at least one COPD exacerbation leading to hospitalisation during the actual treatment period per treatment. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. The median was not estimated due to less than 50% of patients having an event. Hence the number of patients with at least one moderate to severe COPD exacerbation leading to hospitalisation is presented. (NCT02296138)
Timeframe: From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days

InterventionNumber of patients (Number)
Tiotropium 5 Microgram (μg)469
Tiotropium (5 μg) + Olodaterol (5 μg)450

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Number of Patients With at Least One Moderate to Severe COPD Exacerbation During the Actual Treatment Period.

Key secondary endpoint: Number of patients with at least one moderate to severe COPD exacerbation during the actual treatment period per treatment. The actual treatment period was defined as the interval from first in-take of study medication until 1 day after last in-take of study medication. The median was not estimated due to less than 50% of patients having an event. Hence the number of patients with at least one moderate to severe COPD exacerbation is presented. (NCT02296138)
Timeframe: From first in-take of study medication until 1 day after last in-take of study medication, up to 361 days

InterventionNumber of patients (Number)
Tiotropium 5 Microgram (μg)1777
Tiotropium (5 μg) + Olodaterol (5 μg)1746

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Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs)

At day 43 adjusted mean (SE) of average daily duration [minute] of ≥ 4 METs treatment comparisons measured by the activity monitor in the 2 weeks prior to week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: 2 weeks prior to Week 6 per treatment

Interventionminute (Mean)
Tiotropium 5 μg10.206
Tiotropium + Olodaterol 5/5 μg9.914

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Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs)

At day 43 adjusted mean (SE) of average daily duration [minute] of ≥ 3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: 2 weeks prior to Week 6 per treatment

Interventionminute (Mean)
Tiotropium 5 μg44.662
Tiotropium + Olodaterol 5/5 μg45.601

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Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs

At day 43 adjusted mean (SE) of average daily active strength [METs x minute] of >=3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: 2 weeks prior to Week 6 per treatment

InterventionMetabolic equivalents * minutes (Mean)
Tiotropium 5 μg148.647
Tiotropium + Olodaterol 5/5 μg151.067

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60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre)

At day 43 adjusted mean (SE) of 60 minute post-dose slow vital capacity [Litre] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg2.962
Tiotropium + Olodaterol 5/5 μg3.096

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6-minute Walk Distance [Meter]

6-minute walk distance [Meter] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionMeter (m) (Mean)
Tiotropium 5 μg307.356
Tiotropium + Olodaterol 5/5 μg311.524

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30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre)

At day 43 adjusted mean (SE) of 30 minute post-dose forced vital capacity (FVC) [Litre] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 30 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg2.857
Tiotropium + Olodaterol 5/5 μg3.020

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Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose

At day 43 inspiratory capacity at rest measured at 60 minutes post-dose, after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.875
Tiotropium + Olodaterol 5/5 μg1.990

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30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre)

At day 43 adjusted mean (SE) of 30 minute post-dose forced expiratory volume in one second (FEV1) [Litre] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 30 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.169
Tiotropium + Olodaterol 5/5 μg1.275

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Average Number of Step Per Day (Step/Day)

At day 43 adjusted mean (SE) of average number of step per day [step/day] treatment comparisons in measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: 2 weeks prior to Week 6 per treatment

Interventionstep/day (Mean)
Tiotropium 5 μg3550.400
Tiotropium + Olodaterol 5/5 μg3559.901

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Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs)

At day 43 adjusted mean (SE) of average daily duration [minute] of ≥ 2 METs treatment comparison measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: 2 weeks prior to Week 6 per treatment

Interventionminute (Mean)
Tiotropium 5 μg171.935
Tiotropium + Olodaterol 5/5 μg174.192

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Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage III/IV

At day 43 adjusted mean (standard error) of inspiratory capacity [Litre] treatment comparisons after 6 weeks of each treatment for subgroup of GOLD stage III/IV. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.697
Tiotropium + Olodaterol 5/5 μg1.849

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Inspiratory Capacity [Litre] Treatment Comparisons of Subgroup of Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I/II

At day 43 adjusted mean (standard error) of inspiratory capacity [Litre] treatment comparisons after 6 weeks of each treatment for subgroup of GOLD stage I/II. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg2.023
Tiotropium + Olodaterol 5/5 μg2.106

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Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) in-Completer at Baseline Period

At day 43 adjusted mean (standard error) of inspiratory capacity [Litre] test comparisons after 6 weeks of each test for 6MWT in-completer at baseline period. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.744
Tiotropium + Olodaterol 5/5 μg1.830

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Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Treatment Period

At day 43 adjusted mean (standard error) of inspiratory capacity [Litre] test comparisons after 6 weeks of each treatment for 6MWT completer at treatment period. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.940
Tiotropium + Olodaterol 5/5 μg2.072

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Inspiratory Capacity [Litre] Treatment Comparisons of 6-Minute Walk Test (6MWT) Completer at Baseline Period

At day 43 adjusted mean (standard error) of inspiratory capacity [Litre] test comparisons after 6 weeks of each treatment for 6MWT completer at baseline period. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.925
Tiotropium + Olodaterol 5/5 μg2.053

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Inspiratory Capacity [Litre] Test Comparisons of 6-Minute Walk Treatment (6MWT) in-Completer at Treatment Period

At day 43 adjusted mean (standard error) of inspiratory capacity [Litre] test comparisons after 6 weeks of each treatment for 6MWT in-completer at treatment period. Adjusted mean was entered instead of mean in statistical analysis. (NCT02629965)
Timeframe: Day 43, 60 minutes post-dose after 6 weeks of each treatment

InterventionLitre (L) (Mean)
Tiotropium 5 μg1.738
Tiotropium + Olodaterol 5/5 μg1.820

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Trough Forced Vital Capacity (FVC) (in Liter) After 28 Days of Treatment

"This outcome measure presents trough FVC after 28 days of treatment (measurement on Day 29).~The FVC measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement for FVC." (NCT02683109)
Timeframe: Day 29

InterventionLiter (Mean)
T+O 5/53.126
T 5/O 53.121

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Trough Forced Expiratory Volume in 1 Second (FEV1) (in Liter) After 28 Days of Treatment

"This outcome measure presents FEV1 after 28 days of treatment (measurement on Day 29). Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), and was measured at 24 hours (+/- 10 minutes) after trial medication administration at Visit 5.~The FEV1 measurement at Visit 4, which was 24 hours after the last open-label run-in treatment intake and 15 minutes before the first double-blind study drug intake was the baseline measurement." (NCT02683109)
Timeframe: Day 29

InterventionLiter (Mean)
T+O 5/51.422
T 5/O 51.399

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Chronic Obstructive Pulmonary Disease (COPD) Assessment Test™ (CAT) Score on Day 28

"This outcome measure presents COPD assessment test score on Day 28. The COPD Assessment Test™ is a short 8-item questionnaire for assessment and monitoring of COPD health status in routine practice. Its scale is 0-40 (high score = poor health).~The CAT measurement on Visit 4 prior to the first dose of double-blind study drug was the baseline for CAT." (NCT02683109)
Timeframe: Day 28

InterventionScore on scale (Mean)
T+O 5/515.423
T 5/O 515.750

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Change From Period Baseline in the Exercise-isotime Borg CR-10 Rating of Perceived Dyspnea During CWR

Borg rating of perceived shortness of breath (dyspnea) were measured on a category-ratio scale from 0 to 10 (CR-10) during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lower CR-10 score for dyspnea at isotime would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionscores on a scale (Median)
Stiolto Respimat3
Placebo Respimat2.5

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Change From Period Baseline in the Exercise-isotime Borg CR-10 Rating of Perceived Leg Fatigue During CWR

Borg rating of perceived tiredness on the legs (leg fatigue) were measured on a category-ratio scale from 0 to 10 (CR-10) during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lower CR-10 score for leg fatigue at isotime would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionscores on a scale (Median)
Stiolto Respimat3
Placebo Respimat2.5

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Change From Period Baseline in the Exercise-isotime Frontal Lobe Oxygen Saturation During CWR

Tissue saturation of hemoglobin with oxygen is measured by spatially resolved near-infrared spectroscopy from the frontal lobe during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater frontal lobe oxygen saturation at isotime would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

InterventionPercent of hemoglobin saturated with O2 (Median)
Stiolto Respimat62.5
Placebo Respimat62.8

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Change From Period Baseline in the Exercise-isotime in Pulse Oximeter Oxygen Saturation During CWR

Percentage of arterial hemoglobin that is saturated with oxygen, measured using pulse oximetry during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater pulse oximeter oxygen saturation would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionpercent of hemoglobin saturated with O2 (Median)
Stiolto Respimat99.0
Placebo Respimat98.5

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Change From Period Baseline in the Exercise-isotime Inspiratory Capacity During CWR

Inspiratory capacity (IC) measured during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater IC would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

InterventionLiters (Median)
Stiolto Respimat1.91
Placebo Respimat1.88

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Change From Period Baseline in the Exercise-isotime Muscle Oxygen Saturation During CWR

Tissue saturation of hemoglobin plus myoglobin with oxygen is measured by spatially resolved near-infrared spectroscopy from the vastus lateralis muscle during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater muscle oxygen saturation at isotime would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Intervention% of O2 saturated hemoglobin+myoglobin (Median)
Stiolto Respimat54.5
Placebo Respimat53.4

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Change From Period Baseline in the Exercise-isotime Oxygen Uptake (VO2) During CWR

Pulmonary oxygen uptake (VO2) measured during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lesser VO2 would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

InterventionLiters/minute (Median)
Stiolto Respimat1.279
Placebo Respimat1.219

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Change From Period Baseline in the Exercise-isotime Ventilation During CWR

Minute ventilation (VE) measured during constant work rate (CWR) cycling exercise at the time of the shortest duration of each intervention arm (isotime). A lesser VE would reflect a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

InterventionLiters/minute (Median)
Stiolto Respimat50.20
Placebo Respimat45.25

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Change From Period Baseline in the Forced Expiratory Volume in 1 Second (FEV1)

This outcome describes the the effect of the intervention on forced expiratory volume in 1 second (FEV1) during resting spirometry. A greater FEV1 would reflect a positive benefit of the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

InterventionLiters (Median)
Stiolto Respimat1.81
Placebo Respimat1.72

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Change From Period Baseline in the Pre/Post Exercise-induced Decline in Peak Isokinetic Power Normalized to the Measured Muscle Activity (Muscle Fatigue, MF) During CWR

Constant work rate (CWR) exercise causes muscle fatigue (MF) and reduces muscle activation (activation fatigue; AF). The relationship between muscle activity (using EMG) and power is measured at baseline (unfatigued condition). Fatigue is measured by the difference between pre-CWR and post-CWR maximal voluntary isokinetic power i.e. how much maximal voluntary isokinetic power declines during CWR. The fraction of the total fall in voluntary isokinetic power (total fatigue) that is ascribed to reduced muscle activity is then calculated from the reduction in EMG activity. The remainder is ascribed to muscle fatigue (MF) and expressed as a percentage of total fatigue. This measurement was made at peak exercise. A smaller value (%) of MF would be associated with a beneficial response to the intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionpercentage of total fatigue (Median)
Stiolto Respimat20.9
Placebo Respimat25.4

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Exercise Endurance Time During CWR Cycling Exercise

The duration in seconds for which constant work rate (CWR) cycling exercise could be tolerated prior to voluntary termination of exercise. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionseconds (Median)
Stiolto Respimat297
Placebo Respimat274

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The Magnitude of Change Electromyographic (EMG) Muscle Activity (Activation Fatigue, AF) Associated With Stiolto Respimat Compared With Placebo Respimat at Isotime During Constant Work Rate Exercise (CWR)

"Constant work rate (CWR) exercise causes fatigue and reduces muscle activation. The relationship between muscle activation and power is measured at baseline (unfatigued condition). Fatigue is measured by the difference between pre-CWR and post-CWR maximal voluntary isokinetic power i.e. how much maximal voluntary isokinetic power declines during CWR. The fraction of fatigue that is ascribed to reduced muscle activity is then calculated. The magnitude of activation fatigue is measured in EMG activity and expressed in watts at the time of the shortest exercise duration in either study arm, which is termed isotime. A smaller value (in watts) of activation fatigue means that the intervention was associated with a less reduction in EMG activity after a given CWR exercise duration (i.e. at isotime)." (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionwatts (Median)
Stiolto Respimat58
Placebo Respimat50

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The Magnitude of Change in Isokinetic Power (Performance Fatigue, PF) Associated With Stiolto Respimat Compared With Placebo Respimat at Isotime During Constant Work Rate Exercise (CWR)

"Constant work rate (CWR) exercise causes fatigue. Fatigue is measured by the difference between pre-CWR and post-CWR maximal voluntary isokinetic power i.e. how much maximal voluntary isokinetic power declines during CWR. The magnitude of fatigue is measured in watts at the time of the shortest exercise duration in either study arm, which is termed isotime. A smaller value (in watts) of performance fatigue means that the intervention was associated with less fatigue after a given CWR exercise duration (i.e. at isotime)." (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

Interventionwatts (Median)
Stiolto Respimat75
Placebo Respimat77

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Change From Period Baseline in the Exercise-isotime Inspiratory Reserve Volume During CWR

Inspiratory reserve volume (IRV) measured during CWR cycling exercise at the time of the shortest duration of each intervention arm (isotime). A greater IRV would reflect a beneficial response to intervention. (NCT02845752)
Timeframe: Baseline and day 7 of each treatment period

InterventionLiters (Median)
Stiolto Respimat0.54
Placebo Respimat0.46

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Change From Baseline in Intensity of Breathlessness Measured Using the Modified Borg Scale at the End of the 3 Minute (Min) Constant Speed Shuttle Test After 6 Weeks of Treatment.

At 3 min or end of exercise (if 3 min not achieved), patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). The modified Borg scale is 10-point subjective scoring system, in which a patient rates effort of exertion while performing a particular activity. The scale is 0 to 10, the higher the score, the greater the perceived difficulty. Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionUnit on Scale (Least Squares Mean)
Tiotropium 5 Microgram (μg)-0.968
Tiotropium + Olodaterol 5/5 μg-1.325

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Change From Baseline After 6 Weeks of Treatment for Intensity of Breathlessness (MBS-S) at 1, 2 and 2.5 Minute (Min) During the 3 Min Constant Speed Shuttle Test

At 1, 2 and 2.5 min during exercise, patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). At 3 min or end of exercise (if 3 min not achieved), patients were asked to estimate the intensity of breathing discomfort that they were experiencing by matching their subjective estimate to descriptive phrases that best described the intensity of each sensation using the Modified Borg Scale (MBS-S). The modified Borg scale is 10-point subjective scoring system, in which a patient rates effort of exertion while performing a particular activity. The scale is 0 to 10, the higher the score, the greater the perceived difficulty. Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

,
InterventionUnit on Scale (Least Squares Mean)
1 min2 min2.5 min
Tiotropium + Olodaterol 5/5 μg-0.793-1.079-1.164
Tiotropium 5 Microgram (μg)-0.685-0.839-0.846

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Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured Prior to Exercise

Inspiratory Capacity (IC) is a standard measurement for the assessment of lung function. IC measurements were performed prior to the 3min Constant Speed Shuttle Test (CSST) (at rest). Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionLitre (L) (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.279
Tiotropium + Olodaterol 5/5 μg0.464

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Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Standardized (CRQ-SAS) Dyspnoea Domain Score

CRQ-SAS was questionnaire to assess patients' perception of COPD and measures the impact of COPD on their life. This version was derived from the original CRQ tool & therefore, is scored on 7-point Likert-type scale (1: maximum impairment to 7: no impairment) for each 4 domains covering: dyspnea, fatigue, emotional function & mastery. The CRQ-SAS refers to the CRQ-Self-administered standardized format & contains 20 questions. The first part of the questionnaire contains 5 standardized dyspnea questions and the patients must indicate how much shortness of breath they have experienced while performing each of these 5 activities. The scores for each question of each domain were added together and divided by the number of questions answered in each domain. The higher scores indicate better health-related quality of life in the respective domain. Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionUnit on Scale (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.325
Tiotropium + Olodaterol 5/5 μg0.415

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Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Expiratory Volume

Forced Expiratory Volume in 1st second (FEV1) is a standard measurement for the assessment of lung function. The best of 3 efforts was defined as the highest FEV1, each obtained on any of 3 manoeuvres meeting the American Thoracic Society (ATS) criteria (to a maximum of 5 attempts). Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionLitre (L) (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.163
Tiotropium + Olodaterol 5/5 μg0.318

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Change From Baseline After 6 Weeks of Treatment for 1 Hour Post-dose Forced Vital Capacity

Forced Vital Capacity (FVC) is a standard measurement for the assessment of lung function. The best of 3 efforts was defined as the highest FVC, each obtained on any of 3 manoeuvres meeting the American Thoracic Society (ATS) criteria (to a maximum of 5 attempts). Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionLitre (L) (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.258
Tiotropium + Olodaterol 5/5 μg0.459

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Change From Baseline After 6 Weeks of Treatment for Inspiratory Capacity Measured at the End of Exercise

Inspiratory Capacity (IC) is a standard measurement for the assessment of lung function. IC measurements were performed at the end of the 3min Constant Speed Shuttle Test (CSST). Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionLitre (L) (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.256
Tiotropium + Olodaterol 5/5 μg0.322

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Change From Baseline After 6 Weeks of Treatment for Chronic Respiratory Questionnaire - Self Administered Individualized (CRQ-SAI) Dyspnoea Domain Score

CRQ-SAI refers to the CRQ-Self-administered individualized format as it contains a dyspnea domain that is individualized to each patient. This version was derived from the original CRQ tool & therefore, is scored on 7-point Likert-type scale (1: maximum impairment to 7: no impairment) for each 4 domains covering: dyspnea, fatigue, emotional function & mastery. Dyspnea items may be selected from list of 26 suggested items or written in by the patients. The patients are asked to select up to 5 activities associated with breathlessness that they perform frequently and are most important to them. The scores for each question of each domain were added together and divided by the number of questions answered in each domain. The higher scores indicate better health-related quality of life in the respective domain. Measure type is actually Adjusted Mean Change from Baseline. (NCT02853123)
Timeframe: Baseline and week 6

InterventionUnit on Scale (Least Squares Mean)
Tiotropium 5 Microgram (μg)0.640
Tiotropium + Olodaterol 5/5 μg0.610

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Percentage of Subjects With Any Adverse Event (AE) in the Long-term Safety Analysis Set

"An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.~Percentage of participants with any AE is reported. Percentages were rounded to two decimal places." (NCT02864407)
Timeframe: From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days.

Interventionpercentage of partcipants (Number)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)22.88

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Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Effectiveness Analysis Set

Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. (NCT02864407)
Timeframe: At Week 24 (±2 weeks).

Interventionunits on a scale (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)-0.18

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Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Long-term Effectiveness Analysis Set

Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. (NCT02864407)
Timeframe: At Week 24 (±2 weeks).

Interventionunits on a scale (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)-0.31

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Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Effectiveness Analysis Set

Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. (NCT02864407)
Timeframe: At Week 52 (±2 weeks).

Interventionunits on a scale (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)-0.39

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Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Long-term Effectiveness Analysis Set

Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. (NCT02864407)
Timeframe: At Week 52 (±2 weeks).

Interventionunits on a scale (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)-0.44

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Percentage of Subjects With Any Adverse Drug Reaction, Serious Adverse Drug Reaction, Unexpected Adverse Drug Reaction, Unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction Leading to Discontinuation

"An adverse drug reaction (ADR) was defined as a response to a medicinal product which is noxious and unintended. Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility. Adverse reactions may arise from use of the product within or outside the terms of the marketing authorization or from occupational exposure. Conditions of use outside the marketing authorization include off label use, overdose, misuse, abuse and medication errors. Investigator was primarily responsible to assess ADR relatedness.~An ADR was assessed as unexpected if not listed in Local Product Information (LPI) and Company Core Data Sheet (CCDS).~Percentage of subjects with any Adverse Drug Reaction, serious Adverse Drug Reaction, unexpected Adverse Drug Reaction, unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction leading to discontinuation is reported. Percentages were rounded to two decimal places." (NCT02864407)
Timeframe: From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days.

Interventionpercentage of participants (Number)
Any Adverse Drug ReactionSerious Adverse Drug ReactionUnexpected Adverse Drug ReactionUnexpected Serious Adverse Drug ReactionAdverse Drug Reaction leading to discontinuation
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)2.870.161.160.131.32

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Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation

"An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.~An adverse event was assessed as unexpected if not listed in Local Product Information (LPI) and Company Core Data Sheet (CCDS).~Percentage of subjects with any Adverse Event, unexpected Adverse Event, unexpected Serious Adverse Event, Adverse Event leading to discontinuation is reported. Percentages were rounded to two decimal places." (NCT02864407)
Timeframe: From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days.

Interventionpercentage of participants (Number)
Any Adverse EventUnexpected Adverse EventUnexpected Serious Adverse EventAdverse Event leading to discontinuation
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)19.9013.653.482.29

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Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 24 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in post bronchodilator percent predicted FEV1 to Week 24 was calculated as: post bronchodilator percent predicted FEV1 value at Week 24 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline and Week 24 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)3.80

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Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 24 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in post bronchodilator percent predicted FEV1 to Week 24 was calculated as: post bronchodilator percent predicted FEV1 value at Week 24 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline and Week 24 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)5.19

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Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 52 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in post bronchodilator percent predicted FEV1 to Week 52 was calculated as: post bronchodilator percent predicted FEV1 value at Week 52 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline and Week 52 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)4.52

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Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 52 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in post bronchodilator percent predicted FEV1 to Week 52 was calculated as: post bronchodilator percent predicted FEV1 value at Week 52 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline and Week 52 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)4.36

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Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 24 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in pre-dose percent predicted FEV1 to Week 24 was calculated as: pre-dose percent predicted FEV1 value at Week 24 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)5.41

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Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 24 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 24 was calculated as: pre-dose percent predicted FEV1 value at Week 24 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)6.13

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Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 52 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 52 was calculated as: pre-dose percent predicted FEV1 value at Week 52 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)4.91

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Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set

"FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 52 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.).~Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 52 was calculated as: pre-dose percent predicted FEV1 value at Week 52 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline." (NCT02864407)
Timeframe: At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks).

Interventionpercentage of predicted FEV1 (Mean)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)4.83

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Effectiveness Rate in the Effectiveness Analysis Set

"Overall evaluation (Improved, unchanged or aggravated) by investigator was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. 'Improved' was assessed as Effective, 'Unchanged, Aggravated' were assessed as Invalid." (NCT02864407)
Timeframe: At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Interventionpercentage of participants (Number)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)65.84

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Effectiveness Rate in the Long-term Effectiveness Analysis Set

"Overall evaluation (Improved, unchanged, aggravated or unassessable) by investigator was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. 'Improved' was assessed as Effective, 'Unchanged, Aggravated' were assessed as Invalid." (NCT02864407)
Timeframe: At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Interventionpercentage of participants (Number)
Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)70.80

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Maximum Measured Concentration of Olodaterol in Plasma (Cmax)

"Cmax, maximum measured concentration of olodaterol in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).~detailed sampling time points: 0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20(hours:minutes) after drug administration." (NCT02969317)
Timeframe: Day 1, 7, 14, 18, 19 and 20

InterventionPicograms per millilitre [pg/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg1.26

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Maximum Measured Concentration of Tiotropium in Plasma (Cmax)

"Cmax, maximum measured concentration of Tiotropium in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).~Detailed sampling time points:0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20 (hours:minutes) after drug administration" (NCT02969317)
Timeframe: Day 1, 7, 14, 18, 19, 20

InterventionPicograms per millilitre [pg/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg6.12

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Maximum Measured Concentration of Tiotropium in Plasma at Steady State (Cmax,ss)

Cmax,ss, maximum measured concentration of olodaterol in plasma at steady state of Tiotropium after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionPicograms per millilitre [pg/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg7.65

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Pre-dose Concentration of Olodaterol in Plasma at Steady State (Cpre,ss)

Cpre,ss, pre-dose concentration of olodaterol in plasma at steady state after multiple dosing at Day 21 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionPicograms per millilitre [pg/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg0.788

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Pre-dose Concentration of Tiotropium in Plasma at Steady State (Cpre,ss)

Cpre,ss, pre-dose concentration of Tiotropium in plasma at steady state after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionPicograms per millilitre [pg/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg1.90

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Time From Dosing to the Maximum Concentration of Olodaterol in Plasma (Tmax)

"Tmax, time from dosing to the maximum concentration of olodaterol in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).~detailed sampling time points: 0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20(hours:minutes) after drug administration." (NCT02969317)
Timeframe: Day 1, 7, 14, 18, 19 and 20

InterventionHour [h] (Median)
Tiotropium+Olodaterol FDC 5 mg/5 mg0.167

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Time From Dosing to the Maximum Concentration of Olodaterol in Plasma at Steady State (Tmax,ss)

Tmax,ss,time from dosing to the maximum concentration of olodaterol in plasma at steady state after multiple dosing at Day 21 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionHour [h] (Median)
Tiotropium+Olodaterol FDC 5 mg/5 mg2.00

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Time From Dosing to the Maximum Concentration of Tiotropium in Plasma at Steady State (Tmax,ss)

Tmax,ss,time from dosing to the maximum concentration of Tiotropium in plasma at steady state after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionHour [h] (Median)
Tiotropium+Olodaterol FDC 5 mg/5 mg0.0830

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Accumulation Ratios in Plasma of Olodaterol (RA,Cmax =Cmax,ss/Cmax)

Accumulation ratios in plasma of olodaterol (RA,Cmax =Cmax,ss/Cmax) after multiple dosing at Day 21 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 1 and Day 21

InterventionRatio (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg1.58

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Accumulation Ratios in Plasma of Tiotropium (RA,Cmax =Cmax,ss/Cmax)

Accumulation ratios in plasma of Tiotropium (RA,Cmax =Cmax,ss/Cmax) after multiple dosing at Visit 4 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 1, 7, 14, 18, 19, 20 and 21

Interventionratio (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg1.29

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Area Under the Concentration Time Curve of Olodaterol in Plasma Over the Time Interval From 0 to 6 Hours at Steady State (AUC0-6,ss)

AUC0-6,ss, area under the concentration time curve of olodaterol in plasma over the time interval from 0 to 6 hours at steady state after multiple dosing at Day 21 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00 (hours:minutes) after drug administration

InterventionPicograms*hour per millilitre [pg*h/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg7.54

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Area Under the Concentration Time Curve of Tiotropium in Plasma Over the Time Interval From 0 to 6 Hours at Steady State (AUC0-6,ss)

AUC0-6,ss, area under the concentration time curve of Tiotropium in plasma over the time interval from 0 to 6 hours at steady state after multiple dosing at Visit 4 of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21:0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00 (hours:minutes) after drug administration

InterventionPicograms*hour per millilitre [pg*h/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg22.0

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Area Under the Concentration-time Curve of Olodaterol in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)

AUCτ,ss, area under the concentration-time curve of olodaterol in plasma at steady state over a uniform dosing interval τ at steady state after multiple dosing at Day 21 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionPicograms*hour per millilitre [pg*h/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg25.5

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Area Under the Concentration-time Curve of Tiotropium in Plasma at Steady State Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)

AUCτ,ss, area under the concentration-time curve of Tiotropium in plasma at steady state over a uniform dosing interval τ at steady state after multiple dosing at Visit 4 is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionPicograms*hour per millilitre [pg*h/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg54.8

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Time From Dosing to the Maximum Concentration of Tiotropium in Plasma (Tmax)

"Tmax, time from dosing to the maximum concentration of Tiotropium in plasma after single inhaled administration of tiotropium+olodaterol FDC 5 mg/5 mgis presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%).~Detailed sampling time points:0:05 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 143:45, 144:20, 311:45, 312:20, 407:45, 408:20, 431:45, 432:20, 455:45, 456:20 (hours:minutes) after drug administration" (NCT02969317)
Timeframe: Day 1, 7, 14, 18, 19, 20

InterventionHour [h] (Median)
Tiotropium+Olodaterol FDC 5 mg/5 mg0.167

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Maximum Measured Concentration of Olodaterol in Plasma at Steady State (Cmax,ss)

Cmax,ss, maximum measured concentration of olodaterol in plasma at steady state of olodaterol after multiple dosing at Visit 4 (day 21) of tiotropium+olodaterol FDC 5 mg/5 mg is presented as unadjusted geometric mean (gMean) and geometric coefficient of variation (gCV) (%). (NCT02969317)
Timeframe: Day 21: 0:15 (hours:minutes) before drug administration and 0:02, 0:05, 0:07, 0:10, 0:20, 0:30, 0:40, 1:00, 2:00, 3:00, 4:00, 6:00, 12:00, 24:00 (hours:minutes) after drug administration

InterventionPicograms per millilitre [pg/mL] (Geometric Mean)
Tiotropium+Olodaterol FDC 5 mg/5 mg2.00

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Baseline Characteristics of New Users of Indacaterol: Age

Baseline characteristics of patients in treatment group by data source: Age (NCT03030638)
Timeframe: Baseline

InterventionYears (Median)
Indacaterol - PHARMO Overall67
Indacaterol - National Health Databases, Denmark69
Indacaterol - IMS RWE LPD GP Panel63
Indacaterol - IMS RWE LPD Pulmonologist Panel68

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Baseline Characteristics of New Users of Olodaterol: Age

Baseline characteristics of patients in treatment group by data source: Age (NCT03030638)
Timeframe: Baseline

InterventionYears (Median)
Olodaterol - PHARMO Overall68
Olodaterol - National Health Databases, Denmark71
Olodaterol - IMS RWE LPD General Practitioner (GP) Panel63
Olodaterol - IMS RWE LPD Pulmonologist Panel67

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Percentage of Off-label Use of Indacaterol Among New Users

Percentage of off-label use of Indacaterol among new users of this medication. Potential off-label are the patients, aged 18 years or older with no recorded COPD diagnosis and no asthma diagnosis. Off-label are the patients, aged 17 years or younger or patients aged 18 years or older with no recorded COPD diagnosis but with a diagnosis of asthma. (NCT03030638)
Timeframe: 01March2014 to 30November2017 up to 30 days after index date, up to 1370 days.

,,,,
InterventionPercentage of participants (Number)
Potential off-labelOff-label
Indacaterol - IMS RWE LPD GP Panel34.911.9
Indacaterol - IMS RWE LPD Pulmonologist Panel20.59.4
Indacaterol - National Health Databases, Denmark66.64.6
Indacaterol - PHARMO Overall61.13.5
Indacaterol - PHARMO-GP29.26.8

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Percentage of Off-label Use of Olodaterol Among New Users

Percentage of off-label use of olodaterol among new users of this medication. Potential off-label are the patients, aged 18 years or older with no recorded Chronic Obstructive Pulmonary Disease (COPD) diagnosis and no asthma diagnosis. Off-label are the patients, aged 17 years or younger or patients aged 18 years or older with no recorded COPD diagnosis but with a diagnosis of asthma. Index date is defined as the date an eligible patient receives the first dispensing of olodaterol or indacaterol during the study period. (NCT03030638)
Timeframe: 01March2014 to 30November2017 up to 30 days after index date, up to 1370 days.

,,,,
InterventionPercentage of participants (Number)
Potential off-labelOff-label
Olodaterol - IMS RWE LPD General Practitioner (GP) Panel33.912.4
Olodaterol - IMS RWE LPD Pulmonologist Panel17.34.9
Olodaterol - National Health Databases, Denmark30.34.4
Olodaterol - PHARMO Overall48.63.5
Olodaterol - PHARMO-GP19.66.2

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Change From Baseline in 1.5 Hour Post Dose Forced Expiratory Volume in 1st Second (FEV1) After 6 Weeks of Treatment

Change from baseline in 1.5 hour post dose Forced Expiratory Volume in 1st second (FEV1) is presented. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionLitre (L) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)0.158
Tiotropium + Olodaterol FDC (T+O 5/5)0.339

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Change From Baseline in Aortic Augmentation Index After 6 Weeks of Treatment

Change from baseline in aortic augmentation index is presented. Augmentation index was derived from brachial pulse wave separation analysis as augmentation pressure (pressure difference between the reflection wave to the ejection wave) divided by central pulse pressure (at the central aortic site) multiplied by 100. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionPercentage of index (%) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)1.723
Tiotropium + Olodaterol FDC (T+O 5/5)1.404

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Change From Baseline in Pulse Pressure After 6 Weeks of Treatment

Change from baseline in pulse pressure is presented. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionmmHg (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)0.170
Tiotropium + Olodaterol FDC (T+O 5/5)0.579

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Change From Baseline in Pulmonary Artery Pulsatility After 6 Weeks of Treatment

Change from baseline in pulmonary artery pulsatility (PAP) is presented. Pulmonary artery pulsatility measurements as measure of arterial stiffness were derived from cine images acquired at end-expiration in planes perpendicular to the thoracic aorta at the level of the pulmonary artery (ascending and descending section of thoracic aorta), abdominal aorta, and perpendicularly to the main, right, and left pulmonary arteries. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionPercentage of PAP (%) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)-0.175
Tiotropium + Olodaterol FDC (T+O 5/5)1.105

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Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVI) in the 6th Week of Treatment

"LVEDVI is normalised left ventricular end diastolic volume, divided by body surface area.~Baseline was defined as the value obtained during the assessment performed in a week prior to Visit 2 (Day 1). The change from baseline was calculated as the value obtained in a week prior to Visits 3 and 4 (end of each treatment periods) minus the baseline value." (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionMillilitre/ meter^2 (mL/m^2) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)2.855
Tiotropium + Olodaterol FDC (T+O 5/5)2.317

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Change From Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % Predicted After 6 Weeks of Treatment

Change from Baseline in Functional Residual Capacity Body Plethysmography (FRCpleth) % predicted is presented. Functional residual capacity, percent predicted is a lung volume at the end of normal expiration assessed/measured by body plethysmography and compared to predicted capacity for such subject, if nonsmoker and without a disease which could compromise their ventilator function, to give a percentage predicted. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionPercentage of FRCpleth (%) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)-10.211
Tiotropium + Olodaterol FDC (T+O 5/5)-18.168

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Change From Baseline in Central Systolic Pressure After 6 Weeks of Treatment

Change from baseline in central systolic pressure is presented. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionmmHg (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)0.202
Tiotropium + Olodaterol FDC (T+O 5/5)2.271

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Change From Baseline in 1.5 Hour Post Dose Forced Vital Capacity (FVC) After 6 Weeks of Treatment

Change from baseline in 1.5 hour post dose Forced Vital Capacity (FVC) is presented. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionLitre (L) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)0.159
Tiotropium + Olodaterol FDC (T+O 5/5)0.445

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Change From Baseline in Aortic Distensibility After 6 Weeks of Treatment

Change from baseline in aortic distensibility is presented. Aortic distensibility measurements as measure of arterial stiffness were derived from cine images acquired at end-expiration in planes perpendicular to the thoracic aorta at the level of the pulmonary artery (ascending and descending section of thoracic aorta), abdominal aorta, and perpendicularly to the main, right, and left pulmonary arteries. (NCT03055988)
Timeframe: Baseline and 6 weeks

InterventionPercentage/millimeter of mercury(%/mmHg) (Least Squares Mean)
Fluticasone Propionate + Salmeterol FDC (F+S 1000/100)-0.006
Tiotropium + Olodaterol FDC (T+O 5/5)-0.005

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Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment

"Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 12 hours (AUC0-12) response (change from baseline) [L] after 12 weeks of treatment.~FEV1 AUC0-12 was calculated as the area under the FEV1-time curve from 0-12 hours post-dose using the trapezoidal rule, divided by the duration (12 hours) and reported in liters. FEV1 AUC0-12 response (change from baseline) was defined as FEV1 AUC0-12 minus baseline FEV1." (NCT03240575)
Timeframe: 1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline. 10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min post morning dose at week 12.

InterventionLitre*hours (L*h) (Mean)
Tiotropium+Olodaterol (5μg/5μg) - Main Study0.237
Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study0.147
Tiotropium+Olodaterol (5μg/5μg) - DH-studyNA
Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-studyNA

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Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment

Peak 0-3 hours Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Peak 0-3h was defined as the maximum value measured within the first three hours post doing. (NCT03240575)
Timeframe: 30 minutes, 1 h, 2h and 3h post dose at baseline and week 12.

InterventionLitre (L) (Mean)
Tiotropium+Olodaterol (5μg/5μg) - Main Study0.341
Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study0.243
Tiotropium+Olodaterol (5μg/5μg) - DH-studyNA
Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-studyNA

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Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment

Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 24 hours (AUC0-24) response (change from baseline) [L] after 12 weeks of treatment. FEV1 AUC0-24 was calculated as the area under the FEV1-time curve from 0-24 hours post-dose using the trapezoidal rule, divided by the duration (24 hours) and reported in liters. FEV1 AUC0-24 response (change from baseline) was defined as FEV1 AUC0-24 mius baseline FEV1. (NCT03240575)
Timeframe: 1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline.10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min, 12h 30 min, 13h, 14h, 22h, 23h, and 24h post morning dose at week 12.

InterventionLitre*hours (L*h) (Mean)
Tiotropium+Olodaterol (5μg/5μg) - Main Study0.174
Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study0.122
Tiotropium+Olodaterol (5μg/5μg) - DH-studyNA
Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-studyNA

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Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment

Trough Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Trough FEV1 was defined as the mean of the FEV1 value measured at 23 hours and at 24 hours after the trial medication administration. Through FEV1 response (change from baseline) was defined as trough FEV1 minus baseline FEV1. (NCT03240575)
Timeframe: At 23 h and 24 h post dose at baseline and at 23h and 24 h post dose at week 12.

InterventionLitre (L) (Mean)
Tiotropium+Olodaterol (5μg/5μg) - Main Study0.118
Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study0.114
Tiotropium+Olodaterol (5μg/5μg) - DH-studyNA
Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-studyNA

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Residual Volume on Day 3

Change in residual volume during treatment (NCT03673670)
Timeframe: Change from pre-dose on Day 1 to the following timepoints: pre-dose, 1.25, 8.25 and 12.25 hours on Day 3 (after the morning dose)

,,
InterventionLiters (Mean)
Pre-dose Day 31.25 hours8.25 hours12.25 hours
1.5 mg RPL554 and Tiotropium/Olodaterol on Day 3-0.323-0.648-0.526-0.353
6 mg RPL554 and Tiotropium/Olodaterol on Day 3-0.313-0.510-0.481-0.236
Placebo and Tiotropium/Olodaterol on Day 3-0.184-0.510-0.471-0.094

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Functional Residual Capacity on Day 3

Change in functional residual capacity during treatment (NCT03673670)
Timeframe: Change from pre-dose on Day 1 to the following timepoints: pre-dose, 1.25, 8.25 and 12.25 hours on Day 3 (after the morning dose)

,,
InterventionLiters (Mean)
1.25 hours8.25 hours12.25 hoursPre-dose on Day 3
1.5 mg RPL554 and Tiotropium/Oldaterol on Day 3-0.490-0.420-0.255-0.278
6 mg RPL554 and Tiotropium/Oldaterol on Day 3-0.408-0.405-0.155-0.206
Placebo and Tiotropium/Oldaterol on Day 3-0.382-0.355-0.075-0.163

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Change From Baseline in Peak FEV1 After Evening Dose on Day 3

Change from baseline FEV1 to peak FEV1 in the 4 hours post-dose after the evening dose on Day 3 (NCT03673670)
Timeframe: Change from pre-dose to each of the ollowing timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4 hours on Day 3 (after the evening dose), with the maximum change reported

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.453
6 mg RPL554 and Tiotropium/Olodaterol0.405
Placebo and Tiotropium/Olodaterol0.324

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Change From Baseline in Peak FEV1 on Day 3

Change from baseline FEV1 to peak FEV1 (measured as the greatest value in the 4 hours post-dose after the morning dose) on Day 3 (NCT03673670)
Timeframe: Change from pre-dose at 5, 15 and 30 minutes and 1, 1.5, 2 & 4 hours on Day 3

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.565
6 mg RPL554 and Tiotropium/Olodaterol0.506
Placebo and Tiotropium/Olodaterol0.519

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Change From Baseline in Peak FEV1 on Day 1

Change from baseline FEV1 to peak FEV1 in the 4 hours post-dose after the morning dose on Day 1 (NCT03673670)
Timeframe: Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4 hours on Day 1 (after the morning dose), with the maximum change reported

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.490
6 mg RPL554 and Tiotropium/Olodaterol0.467
Placebo and Tiotropium/Olodaterol0.445

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Specific Airway Conductance on Day 1

Change in specific airway conductance during treatment (NCT03673670)
Timeframe: Change from pre-dose to 1.25 hours on Day 1 (after the morning dose)

Intervention1/kPa*sec (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol on Day 10.064
6 mg RPL554 and Tiotropium/Olodaterol on Day 10.042
Placebo and Tiotropium/Olodaterol on Day 10.043

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Specific Airway Conductance on Day 3

Change in specific airway conductance during treatment (NCT03673670)
Timeframe: Change from pre-dose on Day 1 to the following timepoints: pre-dose, 1.25, 8.25 and 12.25 hours on Day 3 (after the morning dose)

,,
Intervention1/kPa*sec (Mean)
Pre-dose Day 31.25 hours8.25 hours12.25 hours
1.5 mg RPL554 and Tiotropium/Olodaterol on Day 30.0210.0640.0590.029
6 mg RPL554 and Tiotropium/Olodaterol on Day 30.0460.0500.0480.032
Placebo and Tiotropium/Olodaterol on Day 30.0160.0490.0370.021

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Residual Volume on Day 1

Change in residual volume during treatment (NCT03673670)
Timeframe: Change from pre-dose to 1.25 hours on Day 1 (after the morning dose)

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol on Day 1-0.469
6 mg RPL554 and Tiotropium/Olodaterol on Day 1-0.408
Placebo and Tiotropium/Olodaterol on Day 1-0.377

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Functional Residual Capacity on Day 1

Change in functional residual capacity during treatment (NCT03673670)
Timeframe: Change from pre-dose to 1.25 hours on Day 1 (after the morning dose)

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol on Day 1-0.344
6 mg RPL554 and Tiotropium/Olodaterol on Day 1-0.294
Placebo and Tiotropium/Olodaterol on Day 1-0.277

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Determination of Onset of Action on Day 1

Time to >10% increase in FEV1 from pre-first dose, censored at 2 hours (NCT03673670)
Timeframe: Change from pre-dose to the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2 hours on Day 1 (after the morning dose)

Interventionminutes (Median)
1.5 mg RPL554 and Tiotropium/Olodaterol10.0
6 mg RPL554 and Tiotropium/Olodaterol6.0
Placebo and Tiotropium/Olodaterol11.0

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Change From Baseline to Trough FEV1 on Day 4

Change from baseline to morning trough FEV1 on Day 4 (NCT03673670)
Timeframe: Change from pre-dose on Day 1 to pre-dose on Day 4

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.186
6 mg RPL554 and Tiotropium/Olodaterol0.178
Placebo and Tiotropium/Olodaterol0.150

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Change From Baseline in AUC0-12h FEV1 on Day 1

Change from baseline FEV1 to AUC FEV1 over 12 hours post-dose after the morning dose on Day 1. The endpoint is measured as AUC/interval length (average) and measured in liters (Note: Endpoint is AUC/interval length (average) so the units are in liters.) (NCT03673670)
Timeframe: Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4, 6, 8, 12 hours on Day 1 (after the morning dose)

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.333
6 mg RPL554 and Tiotropium/Olodaterol0.308
Placebo and Tiotropium/Olodaterol0.303

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Change From Baseline in AUC0-12h FEV1 on Day 3

Change from baseline in AUC over 12 hours post-dose after the morning dose on Day 3. The endpoint is measured as AUC/interval length (average) and measured in liters (Note: Endpoint is AUC/interval length (average) so the units are in liters.) (NCT03673670)
Timeframe: Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4, 6, 8, 12 hours on Day 3 (after the morning dose)

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.390
6 mg RPL554 and Tiotropium/Olodaterol0.347
Placebo and Tiotropium/Olodaterol0.337

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Change From Baseline in AUC0-4h FEV1 on Day 3

Change from baseline FEV1 to AUC FEV1 over 4 hours post-dose after the morning dose on Day 3. The endpoint is measured as AUC/interval length (average) and measured in liters. (Note: Endpoint is AUC/interval length (average) so the units are in liters.) (NCT03673670)
Timeframe: Change from pre-dose to each of the following timepoints: 5, 15 and 30 minutes and 1, 1.5, 2, 4 hours on Day 3 (after the morning dose)

InterventionLiters (Mean)
1.5 mg RPL554 and Tiotropium/Olodaterol0.429
6 mg RPL554 and Tiotropium/Olodaterol0.390
Placebo and Tiotropium/Olodaterol0.377

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Rate of Discontinuation of Index Treatment (Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol)

The primary outcome of interest was discontinuation of index treatment (Olodaterol/Tiotropium Bromide or Umeclidinium/Vilanterol), defined as persistence, (i.e. no refill Claim within 60 days [not including treatment Switch, nor death] after end of supply) during follow-up. Persistence was assessed by calculating rates of discontinuation in the matched cohorts using a 60-day allowable gap. Rates of discontinuation are reported as the number of events divided by the number of Person-years at risk. Addition of another treatment to index treatment did not count as discontinuation. (NCT03979807)
Timeframe: From first day after the cohort entry date to the earliest occurence of the outcome (discontinuation or refills), or any censoring criteria (365 days of follow-up without discontinuation, death, disenrollment end of data).

InterventionEvents per 1000 person-years (Number)
Olodaterol/Tiotropium Bromide - Matched Cohort1826.00
Umeclidinium/Vilanterol - Matched Cohort1647.03

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Annualized Rate of Moderate-to-severe Exacerbation

The annualized rate of moderate-to-severe exacerbation was calculated as: total number of episodes of moderate-to-severe exacerbation of all participants divided by the sum of follow-up period [years] of all participants. The corresponding 95% confidence interval was from Poisson regression. (NCT04011475)
Timeframe: Up to 1 year after the index date (Baseline).

Interventionepisodes/patient-year (Number)
Tiotropium+Olodaterol (Group A)0.28
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)0.42
Long-Acting Muscarinic Antagonist (LAMA) (Group C)0.10

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Annualized Rate of Moderate Exacerbation

The annualized rate of moderate exacerbation was calculated as: total number of episodes of moderate exacerbation of all participants divided by the sum of follow-up period [years] of all participants. The corresponding 95% confidence interval was from Poisson regression. (NCT04011475)
Timeframe: Up to 1 year after the index date (Baseline).

Interventionepisodes/patient-year (Number)
Tiotropium+Olodaterol (Group A)0.19
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)0.30
Long-Acting Muscarinic Antagonist (LAMA) (Group C)0.08

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Percentage of Patients Using Rescue Medications

Percentage of patients using rescue medications within 1 year after index date was reported. (NCT04011475)
Timeframe: Up to 1 year after index date (Baseline).

InterventionPercentage of participants (Number)
Tiotropium+Olodaterol (Group A)58.8
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)43.9
Long-Acting Muscarinic Antagonist (LAMA) (Group C)45.6

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Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by COPD Assessment Test (CAT) Score at 12 Months After Index Date

"Change from baseline in pulmonary function after Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Tiotropium+Olodaterol or other LABA+LAMA therapy) or LAMA initiation evaluating by Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) score at 12 months after index date was reported.~The COPD assessment test (CAT) was a simple, 8-item, health status instrument which provided a simple method for assessing the impact of COPD on the patient's health and the quality of life. Each item was on a 6-point scale: 0 (no impact) to 5 (maximum impact). The CAT score ranging from 0 (better health status) to 40 (worse health status) was calculated by summing the points for each item. A decrease in CAT score represents an improvement in health status, whereas an increase in CAT score represents a worsening in health status." (NCT04011475)
Timeframe: At index date (Baseline) and at 12 months after index date.

InterventionScore on a scale (Mean)
Tiotropium+Olodaterol (Group A)0.0
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)1.0
Long-Acting Muscarinic Antagonist (LAMA) (Group C)2.4

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Annualized Rate of Mild Exacerbation

The annualized rate of mild exacerbation was calculated as: total number of episodes of mild exacerbation of all participants divided by the sum of follow-up period [years] of all participants. The corresponding 95% confidence interval was from Poisson regression. (NCT04011475)
Timeframe: Up to 1 year after the index date (Baseline).

Interventionepisodes/patient-year (Number)
Tiotropium+Olodaterol (Group A)0.00
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)0.04
Long-Acting Muscarinic Antagonist (LAMA) (Group C)0.04

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Annualized Rate of Severe Exacerbation

The annualized rate of severe exacerbation was calculated as: total number of episodes of severe exacerbation of all participants divided by the sum of follow-up period [years] of all participants. The corresponding 95% confidence interval was from Poisson regression. (NCT04011475)
Timeframe: Up to 1 year after the index date (Baseline).

Interventionepisodes/patient-year (Number)
Tiotropium+Olodaterol (Group A)0.09
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)0.12
Long-Acting Muscarinic Antagonist (LAMA) (Group C)0.02

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Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by Modified Medical Research Council Dyspnea Scale (mMRC) at 12 Months After Index Date

"Change from baseline in pulmonary function after Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Tiotropium+Olodaterol or other LABA+LAMA therapy) or LAMA initiation evaluating by modified Medical Research Council dyspnea scale (mMRC) at 12 months after index date is reported.~Modified Medical Research Council dyspnea scale (mMRC) is a 5 points scale measuring the severity of dyspnea of patients. The scale ranges from 0 (better outcome) to 4 (worse outcome). The higher the scale value, the more severe the dyspnea is. If mMRC scale of the patient was > 2, it means the patient may suffer from dyspnea." (NCT04011475)
Timeframe: At index date (baseline) and at 12 months after index date

InterventionScore on a scale (Mean)
Tiotropium+Olodaterol (Group A)0.1
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)0.1
Long-Acting Muscarinic Antagonist (LAMA) (Group C)0.2

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Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by Post-bronchodilator Forced Expiratory Volume in One Second (Post-FEV1) at 12 Months After Index Date

"Change from baseline in pulmonary function after Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Tiotropium+Olodaterol or other LABA+LAMA therapy) or LAMA initiation evaluating by post-bronchodilatorForced Expiratory Volume in one second (Post-FEV1) at 12 months after index date was reported.~Spirometry was the most common tool to evaluate the lung function of patients with respiratory disease. Among the results of spirometry, post-bronchodilator Forced Expiratory Volume in one second was used for assisting in the diagnosis, determining disease severity, and following up the prognosis." (NCT04011475)
Timeframe: At index date (Baseline) and at 12 months after index date.

Interventionmilliliter (Mean)
Tiotropium+Olodaterol (Group A)-142.0
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)20.0
Long-Acting Muscarinic Antagonist (LAMA) (Group C)-2.1

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Change From Baseline in Pulmonary Function After LABA+LAMA or LAMA Initiation Evaluating by Post-bronchodilator Forced Volume Vital Capacity (Post-FVC) at 12 Months After Index Date

"Change from baseline in pulmonary function after Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Tiotropium+Olodaterol or other LABA+LAMA therapy) or LAMA initiation evaluating by post-bronchodilator Forced Volume Vital Capacity (Post-FVC) at 12 months after index date was reported.~Spirometry was the most common tool to evaluate the lung function of patients with respiratory disease. Among the results of spirometry, post-bronchodilator Forced Volume Vital Capacity was used for assisting in the diagnosis, determining disease severity, and following up the prognosis." (NCT04011475)
Timeframe: At index date (Baseline) and at 12 months after index date.

Interventionmilliliter (Mean)
Tiotropium+Olodaterol (Group A)-74.0
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)134.5
Long-Acting Muscarinic Antagonist (LAMA) (Group C)63.7

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Incidence of Patients Escalating Therapy (From Single/Dual to Dual/Triple Therapy)

Incidence of patients escalating therapy, from single/dual to dual/triple therapy such as receiving Long-Acting Muscarinic Antagonist (LAMA) escalated to dual therapy or receiving LABA+LAMA (Tiotropium+Olodaterol) escalated to triple therapy(LABA+LAMA+inhaled corticosteroids (ICS)), within 1 year after the index date was reported. (NCT04011475)
Timeframe: Up to 1 year after the index date (Baseline).

InterventionParticipants (Count of Participants)
Tiotropium+Olodaterol (Group A)10
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)17
Long-Acting Muscarinic Antagonist (LAMA) (Group C)19

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Number of Participants With Moderate-to-severe Acute Exacerbation

Number of participants with moderate-to-severe acute exacerbation within 1 year after the index date was reported. (NCT04011475)
Timeframe: Up to 1 year after the index date (Baseline).

InterventionParticipants (Count of Participants)
Tiotropium+Olodaterol (Group A)20
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)22
Long-Acting Muscarinic Antagonist (LAMA) (Group C)9

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Percentage of Patients Receiving Dual Therapy Escalated to Triple Therapy or LAMA Escalated to Dual Therapy

Percentage of patients receiving dual therapy (Tiotropium+Olodaterol or other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) therapy) escalated to triple therapy (LABA+LAMA + inhaled corticosteroids (ICS)) or LAMA escalated to dual therapy (LABA + LAMA) was reported. (NCT04011475)
Timeframe: Up to 1 year after index date (Baseline).

InterventionPercentage of participants (Number)
Tiotropium+Olodaterol (Group A)8.8
Other Long-Acting Beta-Agonist (LABA)+Long-Acting Muscarinic Antagonist (LAMA) (Group B)14.9
Long-Acting Muscarinic Antagonist (LAMA) (Group C)16.7

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Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Alternative Case Definition) to Triple Therapy

"Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (alternative case definition) to triple therapy.~Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.~Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination." (NCT04138758)
Timeframe: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.

Interventionevents per 1,000 Person-days (Number)
Tiotropium + Olodaterol2.16
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy5.67

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

"Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation after cohort entry. The event was defined as follows:~Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD.~or Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid." (NCT04138758)
Timeframe: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to one year after cohort entry.

InterventionEvents per 1,000 Person-days (Number)
Tiotropium + Olodaterol1.63
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy2.43

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Incidence Rate of First Hospitalization for Community-acquired Pneumonia

Incidence rate of first hospitalization for community-acquired pneumonia (serious pneumonia). Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. (NCT04138758)
Timeframe: From cohort entry (index date) until the occurrence of first hospitalization for community-acquired pneumonia (serious pneumonia). Up to one year after cohort entry.

Interventionevents per 1,000 Person-days (Number)
Tiotropium + Olodaterol0.23
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy0.34

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Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Alternative Case Definition) to Triple Therapy

"Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy.~Based on feedback from clinical experts during review of study results, an alternative post-hoc definition was also assessed in which initiation of any treatment including simultaneous LABA (long-acting beta agonist) /LAMA (Long-acting Muscarinic Antagonists) /ICS (inhaled corticosteroid therapy) use in free or fixed combination was counted as an outcome." (NCT04138758)
Timeframe: From cohort entry (index date) until the escalation, up to one year after cohort entry.

Interventionevents per 1,000 Person-days (Number)
Tiotropium + Olodaterol0.57
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy3.14

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Incidence Rate of Any Element of a Composite Outcome Including Exacerbation, Hospitalization for Pneumonia, or Escalation (Original Case Definition) to Triple Therapy

"Incidence rate of any element of a composite outcome including exacerbation, hospitalization for pneumonia, or escalation (original case definition) to triple therapy.~Exacerbation was defined as follows: Severe exacerbation: Hospitalization with a principal discharge diagnosis of COPD. Moderate exacerbation: An emergency department (ED) visit with a discharge diagnosis of COPD, or, an antibiotic for a respiratory condition dispensed the same day as an oral corticosteroid.~Pneumonia was defined using ICD-9-CM diagnoses and ICD-10 diagnosis codes. Escalation was defined as the addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy." (NCT04138758)
Timeframe: From cohort entry (index date) until exacerbation, hospitalization (for community-acquired pneumonia) or escalation, up to one year after cohort entry.

Interventionevents per 1,000 Person-days (Number)
Tiotropium + Olodaterol2.14
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy5.45

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Incidence Rate of the First Date of a Pharmacy Dispensing Indicating Escalation (Original Case Definition) to Triple Therapy

Incidence rate of the first date of a pharmacy dispensing indicating escalation to triple therapy, (i.e., addition of Inhaled Corticosteroids to Tiotropium and Olodaterol or a Long-acting Muscarinic Antagonists to long-acting beta agonist / inhaled corticosteroid therapy). (NCT04138758)
Timeframe: From cohort entry (index date) until the escalation, up to one year after cohort entry.

Interventionevents per 1,000 Person-days (Number)
Tiotropium + Olodaterol0.54
Long-acting Beta Agonist / Inhaled Corticosteroid Therapy2.90

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation was reported. Time to the first Chronic obstructive pulmonary disease (COPD) exacerbation will be measured from cohort entry until the occurrence of a hospitalization for COPD (severe exacerbation) or Emergency Department (ED) visit for COPD with the prescription of an antibiotic and/or an oral corticosteroid on the same day (moderate exacerbation). (NCT04184297)
Timeframe: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to 1 year after cohort entry.

InterventionEvents per 1000 person-days (Number)
Tiotropium+Olodaterol1.32
LABA/LAMA/ICS1.14

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Overall Incidence Rate of Hospitalization for Community-acquired Pneumonia (Serious Pneumonia)

Overall incidence rate of first hospitalization for community-acquired pneumonia (serious pneumonia). (NCT04184297)
Timeframe: From cohort entry (index date) until the occurrence of hospitalization for community-acquired pneumonia (serious pneumonia). Up to 1 year after cohort entry.

InterventionEvents per 1000 person-days (Number)
Tiotropium+Olodaterol0.25
LABA/LAMA/ICS0.24

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation - Without Exacerbation Within 30 Days Prior to Cohort Entry

Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation excluding participants who had exacerbation within 30 days prior to cohort entry, was reported. Time to the first Chronic obstructive pulmonary disease (COPD) exacerbation will be measured from cohort entry until the occurrenceof a hospitalization for COPD (severe exacerbation) or Emergency Department (ED) visit for COPD with the prescription of an antibiotic and/or an oral corticosteroid on the same day (moderate exacerbation). (NCT04184297)
Timeframe: From cohort entry (index date) until the occurrence of a hospitalization for COPD (severe exacerbation), ED visit for COPD or prescription of an antibiotic and oral corticosteroid on the same day (moderate exacerbation). Up to 1 year after cohort entry.

InterventionEvents per 1000 person-days (Number)
Tiotropium+Olodaterol1.18
LABA/LAMA/ICS0.99

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Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) After 4 Weeks of Treatment

Change from baseline in trough Forced Expiratory Volume in one second (FEV1) after 4 weeks of treatment. (NCT04223843)
Timeframe: At baseline and at week 4.

InterventionLiter (Mean)
Tio+Olo (5μg/5μg) - Sub-optimal PIFR0.095
Matching Placebo - Sub-optimal PIFR-0.106
Tio+Olo (5μg/5μg ) - Optimal PIFR0.177
Matching Placebo - Optimal PIFR-0.040

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Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) After 4 Weeks of Treatment.

"FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters. Mean is adjusted mean.~A hierarchical testing procedure was used to test the primary endpoint. Each of the tests were considered confirmatory only if all previous tests were successful." (NCT04223843)
Timeframe: At baseline and at week 4: 10 minutes (min) prior and 5 min, 15 min, 30 min and 1 hour (h), 2h and 3h after drug administration, respectively.

InterventionLiter (L) (Mean)
Tio+Olo (5μg/5μg) - Sub-optimal PIFR0.250
Matching Placebo - Sub-optimal PIFR-0.086
Tio+Olo (5μg/5μg ) - Optimal PIFR0.333
Matching Placebo - Optimal PIFR0.012

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Time to Triple Therapy Initiation

"Time to triple therapy initiation (first event per patient) defined as any fixed dose combination of Long-acting muscarinic antagonists (LAMA) / Long-acting beta agonist (LABA) / Inhaled Corticosteroid (ICS) or any concurrent use for 30 consecutive days of the following:~any LAMA/LABA fixed dose combination + any ICS single formulation~any LAMA single formulation + any LABA/ICS fixed dose combination~any LAMA single formulation + any LABA single formulation + any ICS single formulation.~Patients will be censored if they had an occurrence of any of the following: outcome (initiation of triple therapy), death, or end of data. The analysis will use an intention-to-treat censoring approach, which does not account for treatment change." (NCT04249310)
Timeframe: From index date (cohort entry date) until first occurence of event, up to 42 months.

InterventionDays (Mean)
Tiotropium/Olodaterol (Spiolto®)195.0
Tiotropium (Spiriva®)89.5

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Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

"Time to First Moderate or Severe COPD Exacerbation. Moderate exacerbation is defined as an outpatient visit with a diagnosed code for COPD in any field + a prescription for an oral corticosteroid or an antibiotic for respiratory infections. Severe exacerbations will be defined as a hospitalization with a primary diagnosis for COPD.~Patients will be censored if they had an occurrence of any of the following: outcome (initiation of triple therapy), death, or end of data. The analysis will use an intention-to-treat censoring approach, which does not account for treatment change." (NCT04249310)
Timeframe: From index date until first occurence of event, up to 42 months.

,
InterventionDays (Mean)
Moderate or SevereModerate ExacerbationSevere Exacerbation
Tiotropium (Spiriva®)118.8139.0134.5
Tiotropium/Olodaterol (Spiolto®)116.3125.6134.0

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Number of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

"Number of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations.~Moderate exacerbation is defined as an outpatient visit with a diagnosed code for COPD in any field + a prescription for an oral corticosteroid or an antibiotic for respiratory infections. Severe exacerbations will be defined as a hospitalization with a primary diagnosis for COPD.~Patients will be censored if they had an occurrence of any of the following: outcome (initiation of triple therapy), death, or end of data. The analysis will use an intention-to-treat censoring approach, which does not account for treatment change." (NCT04249310)
Timeframe: From index date until first occurence of event, up to 42 months.

,
InterventionNumber of Exacerbations (Mean)
Moderate or Severe ExacerbationsModerate ExacerbationsSevere Exacerbations
Tiotropium (Spiriva®)0.080.040.05
Tiotropium/Olodaterol (Spiolto®)0.080.040.05

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Percentage of Patients With Improved / Worsen Condition in Self-care According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months

EQ-5D-5L descriptive system comprises of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Subjects had to indicate their health state by choosing the appropriate level from each dimension. The dimension for self-care is reported in this endpoint. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionPercentage of participants (Number)
Improvement compared to baselineDeterioration compared to baseline
COPD Patients30.593.80

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Percentage of Patients With Adherence to the Medication

Adherence is measured with the Simplified Medication Adherence Questionnaire (SMAQ), which is a short questionnaire including 6 questions, that assess patient adherence to the medication. (NCT04672941)
Timeframe: At 3 months after baseline.

InterventionPercentage of participants (Number)
YesNo
COPD Patients67.2032.80

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Percentage of Patients by Preference for Inhaler

Percentage of patients by preference for inhaler according to Part 2 of the PASAPQ is reported. (NCT04672941)
Timeframe: At 3 months after baseline.

InterventionPercentage of participants (Number)
Spiriva® Handihaler®Spiolto® Respimat®No preference
COPD Patients4.0687.098.85

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Change From Baseline in Patients' Quality of Life (QoL) According to the Total Score of COPD Assessment Test (CAT) at Month 3

The CAT is a patient-completed questionnaire assessing globally the impact of COPD on health status. It contains 8 items, where each item has a score range from 0 to 5. The CAT score is calculated by summing up the scores from the 8 items. CAT score ranges from 0 to 40. Higher score denotes a more severe impact of COPD on a patient's life. CAT score <10 corresponding to mild impact on patients life is usually considered representing patients without impaired health status. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionScore on a scale (Mean)
BaselineChange from baseline
COPD Patients18.41-5.25

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Percentage of Patients With Improved / Worsen Condition Pain/Discomfort According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months

EQ-5D-5L descriptive system comprises of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Subjects had to indicate their health state by choosing the appropriate level from each dimension. The dimension for pain/discomfort is reported in this endpoint. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionPercentage of participants (Number)
Improvement compared to baselineDeterioration compared to baseline
COPD Patients43.554.87

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Total Score in Abbreviated Patient Satisfaction and Preference Questionnaire (PASAPQ)

Calculated from questions 1 to 13 in Part 1 of the PASAPQ. All questions in PASAPQ were answered on a 7-point scale ranging from 1= very dissatisfied to 7 = very satisfied. To calculate the total score, the sum of the 13 items of the two domains (performance and convenience) was transformed to a 0- (least) to 100- (most) point scale which is scaled positively: higher scores represent higher levels of satisfaction. (NCT04672941)
Timeframe: At 3 months after baseline.

InterventionScore on a scale (Mean)
COPD Patients78.74

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Percentage of Patients With Improved / Worsened Condition Mobility According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months

EQ-5D-5L descriptive system comprises of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Subjects had to indicate their health state by choosing the appropriate level from each dimension. The dimension for mobility is reported in this endpoint. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionPercentage of participants (Number)
Improvement compared to baselineDeterioration compared to baseline
COPD Patients44.272.87

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Number of Patients Adherence to Medication of COPD Patients According to the Simplified Medication Adherence Questionnaire (SMAQ) Three-months After the Switch

Number of patients adherence to medication of COPD patients according to the Simplified Medication Adherence Questionnaire (SMAQ) three-months after the switch is reported. (NCT04672941)
Timeframe: At 3 months after baseline.

InterventionParticipants (Count of Participants)
Forget to take the medication for COPD72504161Always take your medication for COPD at the indicated time72504161If feel worse, do you stop taking the medication for COPD?72504161At the last weekend, did you miss your medication?72504161
MissingYesNo
COPD Patients154
COPD Patients1162
COPD Patients1030
COPD Patients286
COPD Patients40
COPD Patients41
COPD Patients1275
COPD Patients53
COPD Patients1263

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Overall Satisfaction of Inhaler

Overall satisfaction according to Question 14 of PASAPQ (Part 1). Question 14 of PASAPQ has a score range from 1= very dissatisfied to 7 = very satisfied. (NCT04672941)
Timeframe: At 3 months after baseline.

InterventionScore on a scale (Mean)
COPD Patients6.15

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Days of Missed Medication for COPD

Days of missed medication for COPD is reported. (NCT04672941)
Timeframe: up to 3 months

Interventiondays (Mean)
COPD Patients1.55

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Willingness to Continue With Inhaler

According to Part 2 of the PASAPQ; willingness to continue is self-reported by the patient by providing a single value between 1 and 100. 0 indicates that the patient is not willing to continue using the inhaler and 100 indicates that the patient is definitely willing to continue. (NCT04672941)
Timeframe: At 3 months after baseline.

InterventionScore on a scale (Mean)
COPD Patients88.39

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Change From Baseline in the Percentage of Patients With CAT≥10 at Month 3

The CAT is a patient-completed questionnaire assessing globally the impact of COPD on health status. It contains 8 items, where each item has a score range from 0 to 5. The CAT score is calculated by summing up the scores from the 8 items. CAT score ranges from 0 to 40. Higher score denotes a more severe impact of COPD on a patient's life. CAT score <10 corresponding to mild impact on patient's life is usually considered representing patients without impaired health status. CAT≥10 refers to impaired health status. The percentages of patients with CAT CAT≥10 at baseline and at Month 3 were reported below. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionPercentage of participants (Number)
COPD Patients - Baseline91.76
COPD Patients - Month 366.12

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Change From Baseline in the Total European Quality of Life-Visual Analogue Scale (EQ-VAS) at Month 3

The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. EQ-VAS score ranges from 0 to 100 where 0 represents the worst state the patient can imagine and 100 the best. Higher scores indicated better health state. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionScore on a scale (Mean)
COPD Patients11.44

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Percentage of Patients With Improved / Worsen Condition Anxiety/Depression According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months

EQ-5D-5L descriptive system comprises of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Subjects had to indicate their health state by choosing the appropriate level from each dimension. The dimension for anxiety/depression is reported in this endpoint. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionPercentage of participants (Number)
Improvement compared to baselineDeterioration compared to baseline
COPD Patients43.274.01

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Change From Baseline of Patients' Dyspnea Status According to the Modified Medical Research Council (mMRC) Scale at Month 3

mMRC is a five-level rating scale ranging from 0 to 4 based on the patient's perception of dyspnea in daily activities. A higher score indicates a higher grade of breathlessness. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionScore on a scale (Mean)
COPD Patients-0.55

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Percentage of Patients With Improved / Worsen Condition Usual Activities According to the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Questionnaire After 3 Months

EQ-5D-5L descriptive system comprises of 5 dimensions-mobility, self-care, usual activities, pain/discomfort & anxiety/depression. Each dimension has 5 levels: not at all (level 1), mild (level 2), moderate (level 3), severe (level 4), extreme/leading to incapacity (level 5), with highest level corresponding to worst outcome. Subjects had to indicate their health state by choosing the appropriate level from each dimension. The dimension for usual activities is reported in this endpoint. (NCT04672941)
Timeframe: At baseline and at 3 months after baseline.

InterventionPercentage of participants (Number)
Improvement compared to baselineDeterioration compared to baseline
COPD Patients43.624.08

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Characteristics of Patients Receiving Second Maintenance Treatment - UK

Characteristics of patients receiving second maintenance treatment from chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy in the United Kingdom (UK) CPRD GOLD database were reported. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

,,,,,,,
InterventionParticipants (Count of Participants)
MaleConcomitant medications - Oral corticosteroids
UK CPRD GOLD - 2MT - ICS3125
UK CPRD GOLD - 2MT - LABA5136
UK CPRD GOLD - 2MT - LABA+ICS191152
UK CPRD GOLD - 2MT - LAMA12771
UK CPRD GOLD - 2MT - LAMA+ICS3741
UK CPRD GOLD - 2MT - LAMA+LABA555356
UK CPRD GOLD - 2MT - LAMA+LABA+ICS383385
UK CPRD GOLD - 2MT - Overall13751066

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Characteristics of Patients Receiving Second Maintenance Treatment - US

Characteristics of patients receiving second maintenance treatment from chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy in the United States (US) IBM MarketScan database were reported. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

,,,,,,,
InterventionParticipants (Count of Participants)
MaleUpper respiratory tract infectionLower respiratory infectionsChronic bronchitisLung fibrosisConcomitant medications - Oral corticosteroidsConcomitant medications - Oral antibiotics
US IBM Marketscan - 2MT - ICS2651961308937355481
US IBM Marketscan - 2MT - LABA41251311114464
US IBM Marketscan - 2MT - LABA+ICS92049736826410110191399
US IBM Marketscan - 2MT - LAMA749343260243798511126
US IBM Marketscan - 2MT - LAMA+ICS733229261275108
US IBM Marketscan - 2MT - LAMA+LABA62830721316543595833
US IBM Marketscan - 2MT - LAMA+LABA+ICS99844237229710511251388
US IBM Marketscan - 2MT - Overall367418421385109538840655399

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Number of Participants With Zero Exacerbations in the Year Prior to the Start of Second Maintenance Therapy - UK

Number of participants with zero exacerbations in the year prior to the start of second maintenance therapy among chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy in the United Kingdom (UK) CPRD GOLD database was reported. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

InterventionParticipants (Count of Participants)
UK CPRD GOLD - 2MT - Overall1351
UK CPRD GOLD - 2MT - ICS34
UK CPRD GOLD - 2MT - LABA63
UK CPRD GOLD - 2MT - LABA+ICS172
UK CPRD GOLD - 2MT - LAMA+LABA590
UK CPRD GOLD - 2MT - LAMA+LABA+ICS299
UK CPRD GOLD - 2MT - LAMA144
UK CPRD GOLD - 2MT - LAMA+ICS49

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Age of the Chronic Obstructive Pulmonary Disease (COPD) Patients at the Time of COPD Diagnosis - US

Age of the chronic obstructive pulmonary disease (COPD) patients at the time of COPD diagnosis from the United States (US) IBM MarketScan was reported by groups stratified according to their COPD diagnosis times (Before versus after the approval of Tiotropium + Olodaterol in 2015). (NCT04926233)
Timeframe: At index date of cohort entry (baseline; time of COPD diagnosis).

InterventionYears (Mean)
US IBM Marketscan - COPD Diagnosis Before Tio+Olo Approval65.6
US IBM Marketscan - COPD Diagnosis After Tio+Olo Approval64.4

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Age of Patients Receiving First Maintenance Treatment - UK

Age of patients receiving first maintenance treatment from chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy in the United Kingdom (UK) CPRD GOLD database was reported. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

InterventionYears (Median)
UK CPRD GOLD - 1MT - Overall68.0
UK CPRD GOLD - 1MT - ICS67.0
UK CPRD GOLD - 1MT - LABA67.0
UK CPRD GOLD - 1MT - LABA+ICS67.0
UK CPRD GOLD - 1MT - LAMA+LABA68.0
UK CPRD GOLD - 1MT - LAMA+LABA+ICS70.0
UK CPRD GOLD - 1MT - LAMA68.0
UK CPRD GOLD - 1MT - LAMA+ICS69.0

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Age of Patients Receiving First Maintenance Treatment - US

Age of chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy in the United States (US) IBM MarketScan database was reported. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

InterventionYears (Mean)
US IBM Marketscan - 1MT - Overall63.0
US IBM Marketscan - 1MT - ICS62.0
US IBM Marketscan - 1MT - LABA67.0
US IBM Marketscan - 1MT - LABA+ICS62.0
US IBM Marketscan - 1MT - LAMA+LABA62.0
US IBM Marketscan - 1MT - LAMA+LABA+ICS63.0
US IBM Marketscan - 1MT - LAMA64.0
US IBM Marketscan - 1MT - LAMA+ICS65.0

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Age of Patients Receiving Second Maintenance Treatment - UK

Age of patients receiving second maintenance treatment from chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy in the United Kingdom (UK) CPRD GOLD database was reported. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

InterventionYears (Median)
UK CPRD GOLD - 2MT - Overall68.0
UK CPRD GOLD - 2MT - ICS68.0
UK CPRD GOLD - 2MT - LABA71.0
UK CPRD GOLD - 2MT - LABA+ICS69.0
UK CPRD GOLD - 2MT - LAMA+LABA68.0
UK CPRD GOLD - 2MT - LAMA+LABA+ICS68.0
UK CPRD GOLD - 2MT - LAMA70.0
UK CPRD GOLD - 2MT - LAMA+ICS68.0

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Age of Patients Receiving Second Maintenance Treatment - US

Age of patients receiving second maintenance treatment from the United States (US) IBM MarketScan database was reported. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

InterventionYears (Median)
US IBM Marketscan - 2MT - Overall64.0
US IBM Marketscan - 2MT - ICS63.0
US IBM Marketscan - 2MT - LABA70.0
US IBM Marketscan - 2MT - LABA+ICS63.0
US IBM Marketscan - 2MT - LAMA+LABA63.0
US IBM Marketscan - 2MT - LAMA+LABA+ICS64.0
US IBM Marketscan - 2MT - LAMA64.0
US IBM Marketscan - 2MT - LAMA+ICS65.0

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Age of the Chronic Obstructive Pulmonary Disease (COPD) Patients at the Time of COPD Diagnosis - UK

Age of the chronic obstructive pulmonary disease (COPD) patients at the time of COPD diagnosis from the the United Kingdom (UK) CPRD GOLD database was reported by groups stratified according to their COPD diagnosis times (Before versus after the approval of Tiotropium + Olodaterol in 2015). (NCT04926233)
Timeframe: At index date of cohort entry (baseline; time of COPD diagnosis).

InterventionYears (Mean)
UK CPRD GOLD - COPD Diagnosis Before Tio+Olo Approval65.82
UK CPRD GOLD - COPD Diagnosis After Tio+Olo Approval66.17

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Charlson Comorbidity Index (CCI) at the Time of COPD Diagnosis

The Charlson Comorbidity Index (CCI) was a method of categorizing comorbidities of patients based on the International Classification of Diseases diagnosis. The CCI score ranged from 0 (better outcome) to 21 (worse outcome). The higher the score, the more fragile/ill the patient was. (NCT04926233)
Timeframe: At index date of cohort entry (baseline; time of COPD diagnosis).

InterventionScore on a scale (Mean)
US IBM Marketscan - Overall1.6
US IBM Marketscan - COPD Diagnosis Before Tio+Olo Approval1.5
US IBM Marketscan - COPD Diagnosis After Tio+Olo Approval1.9
UK CPRD GOLD - Overall1.89
UK CPRD GOLD - COPD Diagnosis Before Tio+Olo Approval1.83
UK CPRD GOLD - COPD Diagnosis After Tio+Olo Approval2.31

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Charlson Comorbidity Index (CCI) of Patients Receiving First Maintenance Treatment - US

The Charlson Comorbidity Index (CCI) was a method of categorizing comorbidities of patients based on the International Classification of Diseases diagnosis. The CCI score ranged from 0 (better outcome) to 21 (worse outcome). The higher the score, the more fragile/ill the patient was. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

InterventionScore on a scale (Mean)
US IBM Marketscan - 1MT - Overall2.0
US IBM Marketscan - 1MT - ICS2.0
US IBM Marketscan - 1MT - LABA2.0
US IBM Marketscan - 1MT - LABA+ICS2.0
US IBM Marketscan - 1MT - LAMA+LABA2.0
US IBM Marketscan - 1MT - LAMA+LABA+ICS2.0
US IBM Marketscan - 1MT - LAMA2.0
US IBM Marketscan - 1MT - LAMA+ICS2.0

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Charlson Comorbidity Index (CCI) of Patients Receiving Second Maintenance Treatment - US

The Charlson Comorbidity Index (CCI) was a method of categorizing comorbidities of patients based on the International Classification of Diseases diagnosis. The CCI score ranged from 0 (better outcome) to 21 (worse outcome). The higher the score, the more fragile/ill the patient was. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

InterventionScore on a scale (Median)
US IBM Marketscan - 2MT - Overall2.0
US IBM Marketscan - 2MT - ICS2.0
US IBM Marketscan - 2MT - LABA3.0
US IBM Marketscan - 2MT - LABA+ICS2.0
US IBM Marketscan - 2MT - LAMA+LABA2.0
US IBM Marketscan - 2MT - LAMA+LABA+ICS2.0
US IBM Marketscan - 2MT - LAMA3.0
US IBM Marketscan - 2MT - LAMA+ICS2.0

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Days Between First and Second Maintenance Therapy - UK

Days between first and second maintenance therapy among chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy in the United Kingdom (UK) CPRD GOLD database were reported. (NCT04926233)
Timeframe: From the index date of first maintenance initiation until the initiation of the second maintenance therapy, up to 10133 days before this study started.

InterventionDays (Median)
UK CPRD GOLD - 2MT - Overall218.0
UK CPRD GOLD - 2MT - ICS239.5
UK CPRD GOLD - 2MT - LABA141.0
UK CPRD GOLD - 2MT - LABA+ICS155.5
UK CPRD GOLD - 2MT - LAMA+LABA284.0
UK CPRD GOLD - 2MT - LAMA+LABA+ICS197.0
UK CPRD GOLD - 2MT - LAMA225.5
UK CPRD GOLD - 2MT - LAMA+ICS158.0

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Days Between First and Second Maintenance Therapy - US

Days between first and second maintenance therapy among the chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy the United States (US) IBM MarketScan database were reported. (NCT04926233)
Timeframe: From the index date of first maintenance initiation until the initiation of the second maintenance therapy, up to 1020 days before this study started.

InterventionDays (Median)
US IBM Marketscan - 2MT - Overall160.0
US IBM Marketscan - 2MT - ICS181.5
US IBM Marketscan - 2MT - LABA176.0
US IBM Marketscan - 2MT - LABA+ICS158.0
US IBM Marketscan - 2MT - LAMA+LABA223.0
US IBM Marketscan - 2MT - LAMA+LABA+ICS143.5
US IBM Marketscan - 2MT - LAMA137.0
US IBM Marketscan - 2MT - LAMA+ICS125.0

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Days Between Index and Initiation of First Maintenance Therapy - UK

Days between index and initiation of first maintenance therapy among the chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy in the United Kingdom (UK) CPRD GOLD database were reported. (NCT04926233)
Timeframe: From index date until initiation of first maintenance therapy, up to 9795 days before this study started.

InterventionDays (Median)
UK CPRD GOLD - 1MT - Overall28.5
UK CPRD GOLD - 1MT - ICS708.0
UK CPRD GOLD - 1MT - LABA43.5
UK CPRD GOLD - 1MT - LABA+ICS32.0
UK CPRD GOLD - 1MT - LAMA+LABA19.0
UK CPRD GOLD - 1MT - LAMA+LABA+ICS19.0
UK CPRD GOLD - 1MT - LAMA22.0
UK CPRD GOLD - 1MT - LAMA+ICS19.0

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Days Between Index and Initiation of First Maintenance Therapy - US

Days between index and initiation of first maintenance therapy among the chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy the United States (US) IBM MarketScan database was reported. (NCT04926233)
Timeframe: From index date until initiation of first maintenance, up to 3368 days before this study started.

InterventionDays (Median)
US IBM Marketscan - 1MT - Overall158.0
US IBM Marketscan - 1MT - ICS242.0
US IBM Marketscan - 1MT - LABA233.0
US IBM Marketscan - 1MT - LABA+ICS165.0
US IBM Marketscan - 1MT - LAMA+LABA116.0
US IBM Marketscan - 1MT - LAMA+LABA+ICS78.0
US IBM Marketscan - 1MT - LAMA136.0
US IBM Marketscan - 1MT - LAMA+ICS85.0

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Number of Participants With Zero Exacerbations in the Year Prior to the Start of First Maintenance Therapy - UK

Number of participants with zero exacerbations in the year prior to the start of first maintenance therapy among the chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy in the United Kingdom (UK) CPRD GOLD database was reported. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

InterventionParticipants (Count of Participants)
UK CPRD GOLD - 1MT - Overall5942
UK CPRD GOLD - 1MT - ICS498
UK CPRD GOLD - 1MT - LABA275
UK CPRD GOLD - 1MT - LABA+ICS712
UK CPRD GOLD - 1MT - LAMA+LABA960
UK CPRD GOLD - 1MT - LAMA+LABA+ICS207
UK CPRD GOLD - 1MT - LAMA3281
UK CPRD GOLD - 1MT - LAMA+ICS9

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Number of Participants With Zero Exacerbations in the Year Prior to the Start of First Maintenance Therapy - US

Number of participants with zero exacerbations in the year prior to the start of first maintenance therapy among the chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy the United States (US) IBM MarketScan database was reported. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

InterventionParticipants (Count of Participants)
US IBM Marketscan - 1MT - Overall26242
US IBM Marketscan - 1MT - ICS3518
US IBM Marketscan - 1MT - LABA183
US IBM Marketscan - 1MT - LABA+ICS12483
US IBM Marketscan - 1MT - LAMA+LABA3818
US IBM Marketscan - 1MT - LAMA+LABA+ICS676
US IBM Marketscan - 1MT - LAMA5515
US IBM Marketscan - 1MT - LAMA+ICS49

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Number of Participants With Zero Exacerbations in the Year Prior to the Start of Second Maintenance Therapy - US

Number of participants with zero exacerbations in the year prior to the start of second maintenance therapy among the chronic obstructive pulmonary disease (COPD) patients initiated their second maintenance therapy the United States (US) IBM MarketScan database was reported. (NCT04926233)
Timeframe: At index date of the second maintenance treatment

InterventionParticipants (Count of Participants)
US IBM Marketscan - 2MT - Overall2361
US IBM Marketscan - 2MT - ICS226
US IBM Marketscan - 2MT - LABA29
US IBM Marketscan - 2MT - LABA+ICS684
US IBM Marketscan - 2MT - LAMA+LABA426
US IBM Marketscan - 2MT - LAMA+LABA+ICS505
US IBM Marketscan - 2MT - LAMA451
US IBM Marketscan - 2MT - LAMA+ICS40

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Characteristics of Patients Receiving First Maintenance Treatment - US

Characteristics of patients receiving first maintenance treatment among chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy in the United States (US) IBM MarketScan database were reported. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

,,,,,,,
InterventionParticipants (Count of Participants)
Upper respiratory tract infectionLower respiratory tract infectionPneumoniaChronic bronchitisLung fibrosisConcomitant medications - Oral corticosteroidsConcomitant medications - Oral antibioticsConcomitant medications - Oxygen therapy
US IBM Marketscan - 1MT - ICS21141160125360323931725047425
US IBM Marketscan - 1MT - LABA874677422215224957
US IBM Marketscan - 1MT - LABA+ICS715145774762264288212240191682094
US IBM Marketscan - 1MT - LAMA2299147421601066405395971161058
US IBM Marketscan - 1MT - LAMA+ICS341629125509616
US IBM Marketscan - 1MT - LAMA+LABA1632885101450220727704645625
US IBM Marketscan - 1MT - LAMA+LABA+ICS4863676512941089291508305
US IBM Marketscan - 1MT - Overall13803852599465161186823272378294580

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Characteristics of Patients Receiving First Maintenance Treatment - UK

Characteristics of patients receiving first maintenance treatment from chronic obstructive pulmonary disease (COPD) patients initiated their first maintenance therapy in the United Kingdom (UK) CPRD GOLD database were reported. (NCT04926233)
Timeframe: At index date of the first maintenance treatment

,,,,,,,
InterventionParticipants (Count of Participants)
Upper respiratory tract infectionLower respiratory tract infection (not pneumonia)Concomitant medications - Oral corticosteroidsConcomitant medications - Oral antibiotics
UK CPRD GOLD - 1MT - ICS454501207480
UK CPRD GOLD - 1MT - LABA16622087204
UK CPRD GOLD - 1MT - LABA+ICS545721453796
UK CPRD GOLD - 1MT - LAMA1946248611402624
UK CPRD GOLD - 1MT - LAMA+ICS71168
UK CPRD GOLD - 1MT - LAMA+LABA541732353797
UK CPRD GOLD - 1MT - LAMA+LABA+ICS143164121224
UK CPRD GOLD - 1MT - Overall3802483523675133

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Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

"Annualized population averages of COPD exacerbations for the categories below are reported:~Any COPD exacerbation~Severe COPD exacerbation (defined as an inpatient admission or an emergency room (ER) visit with a COPD diagnosis code in the primary position; or an inpatient admission or an ER visit with a diagnosis code for acute respiratory failure in the primary position and a COPD diagnosis code in any position; or an inpatient admission or an ER visit with a diagnosis code for acute respiratory failure in the primary position + an inpatient admission or an ER visit within ±7 days with a COPD diagnosis code in any position).~Annualized population averages= ([sum of all exacerbations for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals])." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

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Interventionexacerbations/year (Mean)
Any COPD exacerbationSevere COPD exacerbation
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)0.980.26
Tiotropium Bromide/Olodaterol (TIO/OLO)1.020.28

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All-cause Health Care Resource Utilization

"All-cause health care resource utilization. Annualized population averages of visits for each of the following categories is reported:~Ambulatory visits~Office visits~Outpatient visits~Emergency room visits~Inpatient visits~Other medical visits (included services like independent laboratory, home health, durable medical equipment, etc.) Annualized population averages of visits were calculated as: ([sum of all visits for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals])." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

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Interventionvisits/year (Mean)
Ambulatory visitsOffice visitsOutpatient visitsEmergency room visitsInpatient visitsOther medical visits
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)32.9117.5715.421.390.4810.48
Tiotropium Bromide/Olodaterol (TIO/OLO)32.5417.8014.821.260.4510.09

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Percentage of Patients With 30-day All-cause Readmission After COPD Hospitalization

"Percentage of patients with 30-day all-cause readmission after Chronic Obstructive Pulmonary Disease (COPD) hospitalization is reported.~Hospitalizations were classified as COPD-related if they met either of the following 2 criteria:~≥1 diagnosis of COPD in the primary position any time during the acute inpatient stay; or~≥1 diagnosis of acute respiratory failure in the primary position and a diagnosis of acute exacerbation of COPD in a later position on the same claim during an acute inpatient stay." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

Interventionpercentage of patients (Number)
Tiotropium Bromide/Olodaterol (TIO/OLO)12.04
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)18.25

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COPD or Pneumonia-attributable Health Care Resource Utilization: Pharmacy Fills

"COPD or pneumonia-attributable health care resource utilization: This utilization was calculated for medical claims with a diagnosis for COPD, pneumonia, or acute bronchitis/bronchiolitis in the primary position or a diagnosis for acute respiratory failure in the primary position and a diagnosis for COPD, pneumonia, or acute bronchitis/bronchiolitis in a non-primary position and pharmacy claims for a COPD-related treatment, including COPD-guideline recommended antibiotics.~Annualized population averages for pharmacy claims are calculated as the ([sum of all pharmacy fills for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals]). Wald 95% confidence limits for this ratio used the Taylor expansion to estimate the standard error." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

Interventionpharmacy fills/year (Mean)
Tiotropium Bromide/Olodaterol (TIO/OLO)15.48
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)15.08

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COPD or Pneumonia-attributable Health Care Resource Utilization: Inpatient Days

"COPD or pneumonia-attributable health care resource utilization: This utilization was calculated for medical claims with a diagnosis for COPD, pneumonia, or acute bronchitis/bronchiolitis in the primary position or a diagnosis for acute respiratory failure in the primary position and a diagnosis for COPD, pneumonia, or acute bronchitis/bronchiolitis in a non-primary position and pharmacy claims for a COPD-related treatment, including COPD-guideline recommended antibiotics.~Population annualized averages of inpatient days is reported.~Population annualized averages of inpatient days were calculated as: ([sum of all inpatient days for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals])." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

Interventioninpatient days/year (Mean)
Tiotropium Bromide/Olodaterol (TIO/OLO)2.87
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)3.08

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All-cause Health Care Resource Utilization: Inpatient Days

"All-cause health care resource utilization: Inpatient days. Annualized population averages of inpatient days is reported.~Annualized population averages of inpatient days were calculated as: ([sum of all inpatient days for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals])." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

Interventioninpatient days/year (Mean)
Tiotropium Bromide/Olodaterol (TIO/OLO)4.30
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)4.68

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All-cause Health Care Resource Utilization: Pharmacy Fills

"All-cause health care resource utilization: Pharmacy fills. Annualized population averages for pharmacy fills is reported.~Annualized population averages of pharmacy fills were calculated as:([sum of all pharmacy fills for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals])." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

Interventionpharmacy fills/year (Mean)
Tiotropium Bromide/Olodaterol (TIO/OLO)59.39
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)57.13

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COPD or Pneumonia-attributable Health Care Resource Utilization

"COPD or pneumonia-attributable health care resource utilization: This utilization was calculated for medical claims with a diagnosis for COPD, pneumonia, or acute bronchitis/bronchiolitis in the primary position or a diagnosis for acute respiratory failure in the primary position and a diagnosis for COPD, pneumonia, or acute bronchitis/bronchiolitis in a non-primary position and pharmacy claims for a COPD-related treatment, including COPD-guideline recommended antibiotics.~Population annualized averages of visits in each of the following categories is reported:~Ambulatory visits~Office visits~Outpatient visits~Emergency room visits~Inpatient visits~Other medical visits (independent laboratory, home health, durable medical equipment, etc.)~Population annualized averages of visits were calculated as: ([sum of all visits for all individuals during the follow-up period] / [sum of follow-up on-treatment time in years (365 days) for all individuals])." (NCT05127304)
Timeframe: Follow-up period (started on the day after the index date, with a minimum of 30-days duration (index date + 1 through index date+30) up to a maximum of 12 months duration (index date + 1 through index date +365).

,
Interventionvisits/year (Mean)
Ambulatory visitsOffice visitsOutpatient visitsEmergency room visitsInpatient visitsOther medical visits
Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)4.902.142.770.260.254.27
Tiotropium Bromide/Olodaterol (TIO/OLO)4.202.092.120.290.243.82

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Total Costs of All-cause HCRU

The total annualized costs of all-cause HCRU were calculated for each cohort by totaling the costs for all patients divided by the total follow-up in days, multiplied by 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventiondollars per year (Number)
Stiolto Initiators20849
Trelegy Initiators19384

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Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position) - Among Patients With no Baseline Exacerbation

The incidence rates of pneumonia (pneu.) hospitalization (diagnosis in any position) among patients with no baseline exacerbation were reported. The incidence rate was calculated as totaling the number of pneumonia hospitalization for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionpneu. hospitalization per patient-year (Number)
Stiolto Initiators0.024
Trelegy Initiators0.023

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Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position) - Among Patients With 2 or More Baseline Exacerbations

The incidence rates of pneumonia (pneu.) hospitalization (diagnosis in any position) among patients with 2 or more baseline exacerbations were reported. The incidence rate was calculated as totaling the number of pneumonia hospitalization for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionpneu. hospitalization per patient-year (Number)
Stiolto Initiators0.075
Trelegy Initiators0.072

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Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position) - Among Patients With 0 or 1 Baseline Exacerbation

The incidence rates of pneumonia (pneu.) hospitalization (diagnosis in any position) among patients with 0 or 1 baseline exacerbation were reported. The incidence rate was calculated as totaling the number of pneumonia hospitalization for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionpneu. hospitalization per patient-year (Number)
Stiolto Initiators0.024
Trelegy Initiators0.028

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry

Incidence rate of chronic obstructive pulmonary disease (COPD) exacerbation after cohort entry were reported. The incidence rate was calculated as totaling the number of exacerbation for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionexacerbation per patient-year (Number)
Stiolto Initiators0.28
Trelegy Initiators0.32

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Incidence Rate of Pneumonia Hospitalization (Diagnosis in Any Position)

The incidence rates of pneumonia (pneu.) hospitalization (diagnosis in any position) were reported. The incidence rate was calculated as totaling the number of pneumonia hospitalization for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionpneu. hospitalization per patient-year (Number)
Stiolto Initiators0.025
Trelegy Initiators0.030

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry - Among Patients With no Baseline Exacerbation

Incidence rate of chronic obstructive pulmonary disease (COPD) exacerbation after cohort entry among patients with no baseline exacerbation were reported. The incidence rate was calculated as totaling the number of exacerbation for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionexacerbation per patient-year (Number)
Stiolto Initiators0.25
Trelegy Initiators0.3

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry - Among Patients With 2 or More Baseline Exacerbations

Incidence rate of chronic obstructive pulmonary disease (COPD) exacerbation after cohort entry among patients with 2 or more baseline exacerbations were reported. The incidence rate was calculated as totaling the number of exacerbation for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionexacerbation per patient-year (Number)
Stiolto Initiators0.49
Trelegy Initiators0.58

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Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation After Cohort Entry - Among Patients With 0 or 1 Baseline Exacerbation

Incidence rate of chronic obstructive pulmonary disease (COPD) exacerbation after cohort entry among patients with 0 or 1 baseline exacerbation were reported. The incidence rate was calculated as totaling the number of exacerbation for all patients / total follow-up in days * 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventionexacerbation per patient-year (Number)
Stiolto Initiators0.27
Trelegy Initiators0.31

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Total Costs of COPD or Pneumonia Attributable HCRU

The total annualized costs of COPD or pneumonia attributable HCRU were calculated for each cohort by totaling the costs for all patients divided by the total follow-up in days, multiplied by 365. (NCT05169424)
Timeframe: From index date (i.e. baseline, cohort entry, 15 September 2017) until 31st March 2020, up to 30 months and 16 days.

Interventiondollars per year (Number)
Stiolto Initiators5729
Trelegy Initiators5409

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