| ID Source | ID |
|---|---|
| PubMed CID | 11561674 |
| CHEMBL ID | 514800 |
| CHEBI ID | 78540 |
| SCHEMBL ID | 302992 |
| MeSH ID | M0492206 |
| Synonym |
|---|
| CAS:608141-41-9;APREMILAST |
| HY-12085 |
| cc-10004 |
| apremilast , |
| bdbm50248919 |
| (s)-n-(2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide |
| D08860 |
| otezla (tn) |
| apremilast (jan/usan) |
| 608141-41-9 |
| chebi:78540 , |
| CHEMBL514800 , |
| cc10004 |
| BCP9000311 |
| apremilast (cc-10004) |
| cc 10004 |
| up7qbp99pn , |
| acetamide, n-(2-((1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)- 2,3-dihydro-1,3-dioxo-1h-isoindol-4-yl)- |
| hsdb 8221 |
| apremilast [usan:inn] |
| (+)-n-(2-((1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxo- 2,3-dihydro-1h-isoindol-4-yl)acetamide |
| otezla |
| unii-up7qbp99pn |
| BCP0726000109 |
| FK-0727 |
| CS-0671 |
| apremilast [inn] |
| n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1h-isoindol-4-yl]acetamide |
| apremilast [usan] |
| apremilast [jan] |
| apremilast [orange book] |
| apremilast [vandf] |
| apremilast [who-dd] |
| acetamide, n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1h-isoindol-4-yl]- |
| apremilast [mi] |
| S8034 |
| AKOS016339660 |
| n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-1,3-dioxoisoindol-4-yl]acetamide |
| gtpl7372 |
| (s)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione |
| (s)-n-{2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1h-isoindol-4-yl}-acetamide |
| IMOZEMNVLZVGJZ-QGZVFWFLSA-N |
| SCHEMBL302992 |
| n-{2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1h-isoindol-4-yl}acetamide |
| apremilastum |
| n-{2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1h-isoindol-4-yl}acetamide |
| c22h24n2o7s |
| AC-27650 |
| DB05676 |
| EX-A336 |
| SW219856-1 |
| BCP25283 |
| 4-[[5 pound not7-dihydroxy-2 pound not2-dimethyl-8-(2-methylpropanoyl)chromen-6-yl]methy l]-3 pound not5-dihydroxy-6 pound not6-dimethyl-2-(2-methylpropanoyl)cyclohexa-2 pound not4-dien- 1-one |
| BCP03783 |
| Q2858961 |
| AMY371 |
| DTXSID30976289 |
| CCG-269336 |
| a9l , |
| BA164215 |
| apremilast- bio-x |
| EN300-7423712 |
| Z1837762189 |
| n-(2-((1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-2,3-dihydro-1,3-dioxo-1h-isoindol-4-yl)acetamide |
| acetamide, n-(2-((1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-2,3-dihydro-1,3-dioxo-1h-isoindol-4-yl)- |
| n-(2-((1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxo-2,3-dihydro-1h-isoindol-4-yl)acetamide |
| l04aa32 |
Apremilast is a small molecule approved for the treatment of plaques psoriasis and adult psoriatic arthritis. Recently, this treatment has received marketing authorization for severe and refractory oral aphthosis in Behçet's disease.
Apremilast has been approved by the USA FDA for the treatment of active psoriatic arthritis (PsA) and moderate-to-severe psoriasis (PsO) The drug has been well tolerated in phase I and II clinical trials.
Apremilast seems to inhibit in vitro the fibroblast-to-myofibroblast transition and the profibrotic activity induced by TGFβ1 in cultured human skin fibroblasts by downregulating Smad2/3 and Erk1/2 intracellular signalling pathways. Ap Remilast-induced LRG-1 increase was consistent with the overall lack of efficacy in ankylosing spondylitis.
Apremilast was well tolerated, with generally mild gastrointestinal complaints, which occurred early in the course of the treatment and resolved over time. Treatment with apremilasts improved all HRQOL PROs at Week 16 (vs. placebo) Apremilst treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo.
Apremilast was well tolerated and the reported adverse events were in line with the known safety profile. The number of serious adverse events was not significantly different among the apremilst, secukinumab, ustekinumbe, and placebo groups.
Apremilast was rapidly absorbed (maximum concentration: ~2-3 h postdose), and eliminated according to a monoexponential pattern with a terminal-phase elimination half-life of 8-9 h. The aims of this analysis were to develop a population pharmacokinetic (PPK) model of apremilst based on observed data from phase 1 studies combined with clinical trial data from subjects with moderate to severe psoriasis.
| Excerpt | Reference | Relevance |
|---|---|---|
| "4) and Cmax (from 290 vs." | ( The impact of co-administration of ketoconazole and rifampicin on the pharmacokinetics of apremilast in healthy volunteers. Liu, Y; Palmisano, M; Wan, Y; Wu, A; Zhou, S, 2014) | 0.62 |
| " Pharmacodynamic effects of apremilast on plasma biomarkers associated with inflammation were evaluated in a PALACE 1 substudy." | ( The pharmacodynamic impact of apremilast, an oral phosphodiesterase 4 inhibitor, on circulating levels of inflammatory biomarkers in patients with psoriatic arthritis: substudy results from a phase III, randomized, placebo-controlled trial (PALACE 1). Chen, P; Chopra, R; Fang, L; Schafer, PH; Wang, A, 2015) | 1 |
| "A rapid, sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was developed and validated for the determination and pharmacokinetic investigation of apremilast in rat plasma." | ( Determination of Apremilast in Rat Plasma by UPLC-MS-MS and Its Application to a Pharmacokinetic Study. Chen, LG; Lai, X; Li, T; Pan, Y; Wang, S; Wang, Z, 2016) | 0.96 |
| " Plasma apremilast and metabolite M12 concentrations were determined, and pharmacokinetic parameters were calculated from samples obtained predose and up to 72 hours postdose." | ( Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12. Assaf, M; Liu, Y; Nissel, J; Palmisano, M; Zhou, S, 2016) | 1.12 |
| " The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats." | ( Preparation of sustained release apremilast-loaded PLGA nanoparticles: in vitro characterization and in vivo pharmacokinetic study in rats. Alalaiwe, A; Anwer, MK; Ezzeldin, E; Fatima, F; Iqbal, M; Mohammad, M, 2019) | 0.8 |
| "Finding biomarkers that provide shared link between disease severity, drug-induced pharmacodynamic effects and response status in human trials can provide number of values for patient benefits: elucidating current therapeutic mechanism-of-action, and, back-translating to fast-track development of next-generation therapeutics." | ( Large-scale Analyses of Disease Biomarkers and Apremilast Pharmacodynamic Effects. Ai, J; Eisinger, D; LaBrie, ST; Medvedeva, IV; Schafer, P; Stokes, ME; Trotter, MWB; Yang, R, 2020) | 0.82 |
| "We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long-term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis." | ( Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial. Imafuku, S; Komine, M; Nemoto, O; Ohtsuki, M; Okubo, Y; Petric, R; Schafer, P, 2021) | 1.18 |
| " Apremilast was rapidly absorbed (maximum concentration: ~2-3 h postdose), and eliminated according to a monoexponential pattern with a terminal-phase elimination half-life of 8-9 h." | ( Pharmacokinetics and tolerability of apremilast in healthy Korean adult men. Choi, Y; Huh, KY; Lee, H; Liu, L; Nissel, J; Palmisano, M; Ramirez-Valle, F; Wang, X, 2021) | 1.8 |
| " The aims of this analysis were to develop a population pharmacokinetic (PPK) model of apremilast based on observed data from phase 1 studies combined with clinical trial data from subjects with moderate to severe psoriasis, and to develop exposure-response (E-R) models to determine whether Japanese subjects with moderate to severe psoriasis achieve response to apremilast treatment similar to that observed in non-Japanese, predominantly Caucasian subjects with moderate to severe psoriasis." | ( Population pharmacokinetic and exposure-response analysis of apremilast in Japanese subjects with moderate to severe psoriasis. Imafuku, S; Kassir, N; Komine, M; Nemoto, O; Ohtsuki, M; Okubo, Y; Petric, R, 2021) | 1.09 |
Apremilast can be safely and effectively combined with phototherapy, systemic, and/or biological agents in patients with plaque psoriasis not responding adequately to these agents alone. This pilot study assesses the effect of twice-weekly maintenance doses of Cal/BD foam after 4 weeks of standard once-daily treatment.
| Excerpt | Reference | Relevance |
|---|---|---|
| " This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis." | ( The Use of Methotrexate, Alone or in Combination With Other Therapies, for the Treatment of Palmoplantar Psoriasis. Klufas, DM; Strober, BE; Wald, JM, 2015) | 0.42 |
| "To evaluate the short term-efficacy and safety of apremilast in combination with at least one form of photo-, systemic, or biologic therapy in the treatment of chronic plaque psoriasis." | ( Use of Apremilast in Combination With Other Therapies for Treatment of Chronic Plaque Psoriasis: A Retrospective Study. AbuHilal, M; Shear, N; Walsh, S, 2016) | 1.14 |
| "A total of 81 patients with plaque psoriasis were treated with apremilast in combination with at least 1 other therapy (NB-UVB, methotrexate, acitretin, cyclosporin, etanercept, adalimumab, infliximab, or ustekinumab)." | ( Use of Apremilast in Combination With Other Therapies for Treatment of Chronic Plaque Psoriasis: A Retrospective Study. AbuHilal, M; Shear, N; Walsh, S, 2016) | 1.13 |
| "Apremilast can be safely and effectively combined with phototherapy, systemic, and/or biological agents in patients with plaque psoriasis not responding adequately to these agents alone." | ( Use of Apremilast in Combination With Other Therapies for Treatment of Chronic Plaque Psoriasis: A Retrospective Study. AbuHilal, M; Shear, N; Walsh, S, 2016) | 2.33 |
| " After 24 weeks, patients who responded (decreased Vitiligo Area Scoring Index >30%) were rerandomized to receive apremilast or placebo, combined with twice-weekly NB-UVB for 24 additional weeks." | ( Apremilast in Combination with Narrowband UVB in the Treatment of Vitiligo: A 52-Week Monocentric Prospective Randomized Placebo-Controlled Study. Fontas, E; Khemis, A; Lacour, JP; Montaudié, H; Moulin, S; Passeron, T, 2020) | 2.21 |
| " This pilot study assesses the effect of twice-weekly maintenance doses of Cal/BD foam after 4 weeks of standard once-daily treatment in combination with apremilast." | ( The Maintenance Effect of Calcipotriene 0.05% and Betamethasone Dipropionate 0.064% (Cal/BD) Aerosol Foam in Combination With Apremilast. Kircik, L; Ozyurekoglu, E, 2022) | 1.13 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " This new development may allow for once-daily drug administration and improve both bioavailability and patient compliance." | ( Development of an amorphous based sustained release system for apremilast a selective phosphodiesterase 4 (PDE4) inhibitor. Blass, B; Durig, T; Fassihi, R; Zhang, Q, 2022) | 0.96 |
| " The functionalized nanoparticles could overcome the limitation of poor drug bioavailability and showed a high loading capacity of (45 %) with a controlled release of about (74." | ( Multifunctional nanoparticles based on marine polysaccharides for apremilast delivery to inflammatory macrophages: Preparation, targeting ability, and uptake mechanism. Abdalla, M; Chi, Z; Hamouda, HI; Liu, C; Shabana, S; Sharaf, M, 2022) | 0.96 |
Ten Caucasian individuals (6 male, 4 females; mean age 69,3; range 53-81 years) affected by moderate to severe plaque psoriasis were treated with apremilast. This first-time-in-children phase 2 study supports weight-based ap Remilast dosing for future phase 3 studies of pediatric plaque Psoriasis. Phase III clinical trials are currently underway and will better elucidate appropriate dosing of apremillast.
| Excerpt | Relevance | Reference |
|---|---|---|
| " Phase III clinical trials are currently underway and will better elucidate appropriate dosing of apremilast and further illuminate its side effect profile." | ( Apremilast as a treatment for psoriasis. Feldman, S; Pellerin, M; Shutty, B; West, C, 2012) | 2.04 |
| "Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA." | ( Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. de Vlam, KL; Hu, C; Joos, R; Papp, K; Rodrigues, JF; Schett, G; Stevens, R; Vessey, AR; Wollenhaupt, J, 2012) | 1.25 |
| "Ten Caucasian individuals (6 male, 4 females; mean age 69,3; range 53-81 years) affected by moderate to severe plaque psoriasis (PASI≥10 e/o DLQI≥10 e/O BSA≥10) were treated with apremilast, following dosing regimen of technical data sheet and clinically evaluated both after 12 weeks (T12) and 16 weeks (T16)." | ( Skin involvement in patients with psoriatic arthritis: preliminary results of treatment with apremilast in real world setting. Campanati, A; Diotallevi, F; Molinelli, E; Offidani, A; Radi, G, 2019) | 0.93 |
| " Among 185 randomly assigned intent-to-treat patients at week 12, a dose-response relationship was observed; APR40 (n = 63), but not APR30 (n = 58), led to statistically significant improvements (vs." | ( A Phase 2 Randomized Trial of Apremilast in Patients with Atopic Dermatitis. Chen, M; Estrada, YD; Guttman-Yassky, E; Imafuku, S; Malik, K; Nograles, K; Pavel, AB; Peng, X; Poulin, Y; Shah, N; Simpson, EL; Suarez-Farinas, M; Ungar, B; Wen, HC; Xu, H; Zhou, L, 2019) | 0.8 |
| " Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues." | ( Preparation of sustained release apremilast-loaded PLGA nanoparticles: in vitro characterization and in vivo pharmacokinetic study in rats. Alalaiwe, A; Anwer, MK; Ezzeldin, E; Fatima, F; Iqbal, M; Mohammad, M, 2019) | 0.8 |
| " In most cases, they were mild or moderate in severity and tended to resolve over time with continued dosing and without intervention." | ( [Gastrointestinal side effects of apremilast : Characterization and management]. Beigel, F; Beissert, S; Gerdes, S; Homey, B; Körber, A; Mössner, R; Pinter, A; Radtke, MA; Staubach-Renz, P, 2019) | 0.79 |
| " Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults." | ( Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study. Barcellona, C; Becker, EM; de Lucas, R; Fiorillo, L; Hong, Y; Maes, P; Paller, AS; Paris, M; Zhang, W; Zhang, Z, 2020) | 1.06 |
| "This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis." | ( Pharmacokinetics and safety of apremilast in pediatric patients with moderate to severe plaque psoriasis: Results from a phase 2 open-label study. Barcellona, C; Becker, EM; de Lucas, R; Fiorillo, L; Hong, Y; Maes, P; Paller, AS; Paris, M; Zhang, W; Zhang, Z, 2020) | 1.08 |
| "Of the American and European guidelines available for use of apremilast, several organizations are in agreement regarding the dosage of apremilast, but there are significant disagreements concerning matters such as medication indication, pretreatment laboratory testing, and contraindications to therapy." | ( Comparison of psoriasis guidelines for use of apremilast in the United States and Europe: a critical appraisal and comprehensive review. Ghamrawi, RI; Ghiam, N; Wu, JJ, 2022) | 1.22 |
| " The drug’s simple dosing schedule with mild side effect profile makes it a practical option for patients as combination therapy." | ( Review of Apremilast Combination Therapies in the Treatment of Moderate to Severe Psoriasis. Ivanic, MG; Liao, W; Thatiparthi, A; Walia, S; Wu, JJ, 2021) | 1.02 |
| " Twice-weekly maintenance application of topical Cal/BD aerosolized foam has recently been shown to prolong time to remission and is associated with fewer relapses in patients initially treated with standard dosing of the formulation." | ( The Maintenance Effect of Calcipotriene 0.05% and Betamethasone Dipropionate 0.064% (Cal/BD) Aerosol Foam in Combination With Apremilast. Kircik, L; Ozyurekoglu, E, 2022) | 0.93 |
| Role | Description |
|---|---|
| phosphodiesterase IV inhibitor | An EC 3.1.4.53 (3',5'-cyclic-AMP phosphodiesterase) inhibitor that specifically blocks the action of phosphodiesterase IV. |
| non-steroidal anti-inflammatory drug | An anti-inflammatory drug that is not a steroid. In addition to anti-inflammatory actions, non-steroidal anti-inflammatory drugs have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. |
| [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] | |
| Class | Description |
|---|---|
| aromatic ether | Any ether in which the oxygen is attached to at least one aryl substituent. |
| N-acetylarylamine | An acetamide where at at least one of the amide hydrogens is substituted by an aryl group. RNHAc where R is an aryl group. |
| sulfone | An organosulfur compound having the structure RS(=O)2R (R =/= H). |
| phthalimides | A dicarboximide that is phthalimide or derivatives obtained from it by the formal replacement of one or more hydrogens. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Cytochrome P450 1A2 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 1.7740 | 10.0000 | AID395577 |
| Cytochrome P450 3A4 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0001 | 1.7536 | 10.0000 | AID395581 |
| Cytochrome P450 2D6 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 2.0151 | 10.0000 | AID395580 |
| Cytochrome P450 2C9 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 2.8005 | 10.0000 | AID395578 |
| cAMP-specific 3',5'-cyclic phosphodiesterase 4A | Homo sapiens (human) | IC50 (µMol) | 0.0860 | 0.0000 | 1.0680 | 10.0000 | AID1598960; AID1720007; AID395573 |
| Cytochrome P450 2C19 | Homo sapiens (human) | IC50 (µMol) | 10.0000 | 0.0000 | 2.3983 | 10.0000 | AID395579 |
| cAMP-specific 3',5'-cyclic phosphodiesterase 4B | Homo sapiens (human) | IC50 (µMol) | 0.0590 | 0.0000 | 1.1040 | 10.0000 | AID1455744; AID1596278; AID1598195; AID1598960; AID1713828; AID1720007; AID395573 |
| cAMP-specific 3',5'-cyclic phosphodiesterase 4C | Homo sapiens (human) | IC50 (µMol) | 0.0860 | 0.0000 | 1.4651 | 10.0000 | AID1598960; AID1720007; AID395573 |
| cAMP-specific 3',5'-cyclic phosphodiesterase 4D | Homo sapiens (human) | IC50 (µMol) | 0.1235 | 0.0000 | 1.1463 | 10.0000 | AID1596274; AID1598243; AID1598959; AID1598960; AID1605517; AID1651548; AID1720007; AID395573 |
| Carboxylic ester hydrolase | Rattus norvegicus (Norway rat) | IC50 (µMol) | 10.0000 | 0.0004 | 1.4811 | 9.8700 | AID395578 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1598904 | Permeability across apical to basal side in human Caco2 cells assessed as drug recovery measured after 95 mins by LC-MS/MS analysis | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1713830 | Inhibition of PDE-4 in human PBMC assessed as LPS-induced TNFalpha production at 100 nM incubated for 15 mins followed by LPS stimulation and measured after 18 hrs by ELISA relative to control | 2016 | Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22 | In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors. |
| AID1596321 | Inhibition of recombinant N-terminal GST tagged human PDE4A4B (2-end aa) expressed in Sf9 cells using FAM-cAMP as substrate at 10xIC50 incubated for 60 mins by fluorescence plate reader analysis | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID1598907 | Apparent permeability across basal to apical side in human Caco2 cells measured after 95 mins by LC-MS/MS analysis | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1719476 | Toxicity in imiquimod-induced Harlan Balb/c mouse model of psoriasis assessed as effect on body weight at 10 mg/kg, po BID for 7 days | 2021 | Bioorganic & medicinal chemistry, 03-15, Volume: 34 | Discovery of benzo[f]pyrido[4,3-b][1,4]oxazepin-10-one derivatives as orally available bromodomain and extra-terminal domain (BET) inhibitors with efficacy in an in vivo psoriatic animal model. |
| AID1222793 | Dissociation constant, pKa of the compound | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Which metabolites circulate? |
| AID1598244 | Inhibition of recombinant human His6-tagged PDE4D2 expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID1598909 | Efflux ratio of apparent permeability across basal to apical side over apical to basal side in human Caco2 cells measured after 95 mins by LC-MS/MS analysis | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID393500 | Oral bioavailability in rat at 10 mg/kg | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1598241 | Inhibition of recombinant human His6-tagged PDE4D3 UCR1 S54D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvat | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID1598193 | Inhibition of recombinant human wild-type His6-tagged PDE4D7 UCR1 domain (S129 residues) expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by ye | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID395583 | Cmax in rat at 5 mg/kg, iv | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1713828 | Inhibition of human PDE4B using [3H]cAMP as substrate incubated for 5 mins followed by substrate addition and measured after 10 mins by scintillation proximity assay | 2016 | Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22 | In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors. |
| AID1598905 | Permeability across basal to apical side in human Caco2 cells assessed as drug recovery measured after 95 mins by LC-MS/MS analysis | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1596319 | Inhibition of recombinant N-terminal GST-tagged full length human PDE4A1A expressed in Sf9 cells using cAMP as substrate at 10xIC50 incubated for 60 mins by fluorescence plate reader analysis | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID1598243 | Inhibition of recombinant human His6-tagged PDE4D2 expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID395579 | Inhibition of CYP2C19 | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID395582 | Protein binding in human plasma | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1713826 | Inhibition of human PDE4B using [3H]CAMP as substrate at 1000 nM incubated for 5 mins followed by substrate addition and measured after 10 mins by scintillation proximity assay relative to control | 2016 | Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22 | In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors. |
| AID1596274 | Inhibition of PDE4D (unknown origin) | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID1598242 | Inhibition of recombinant human His6-tagged PDE4D3 UCR1 S54D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvat | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID395573 | Inhibition of human PDE4 | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1719474 | Protection against imiquimod-induced Harlan Balb/c mouse model of psoriasis assessed as decrease in ear thickness at 10 mg/kg, po administered BID for 7 days measured on day 8 by dial gauge micrometer analysis | 2021 | Bioorganic & medicinal chemistry, 03-15, Volume: 34 | Discovery of benzo[f]pyrido[4,3-b][1,4]oxazepin-10-one derivatives as orally available bromodomain and extra-terminal domain (BET) inhibitors with efficacy in an in vivo psoriatic animal model. |
| AID1605517 | Inhibition of PDE4D2 (unknown origin) | 2020 | Journal of medicinal chemistry, 03-26, Volume: 63, Issue:6 | Discovery and Optimization of α-Mangostin Derivatives as Novel PDE4 Inhibitors for the Treatment of Vascular Dementia. |
| AID1713831 | Inhibition of PDE-4 in human PBMC assessed as LPS-induced TNFalpha production incubated for 15 mins followed by LPS stimulation and measured after 18 hrs by ELISA relative to control | 2016 | Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22 | In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors. |
| AID1596276 | Inhibition of recombinant N-terminal GST tagged human PDE4A4B (2-end aa) expressed in Sf9 cells using FAM-cAMP as substrate at 0.1xIC50 incubated for 60 mins by fluorescence plate reader analysis | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID393497 | Cmax in rat at 10 mg/kg, po | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1596297 | Inhibition of recombinant N-terminal GST-tagged full length human PDE4A1A expressed in Sf9 cells using cAMP as substrate at 1xIC50 incubated for 60 mins by fluorescence plate reader analysis | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID1598906 | Apparent permeability across apical to basal side in human Caco2 cells measured after 95 mins by LC-MS/MS analysis | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID395581 | Inhibition of CYP3A4 | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1598960 | Inhibition of PDE4 in human PBMC assessed as reduction in LPS-stimulated TNFalpha production | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID395578 | Inhibition of CYP2C9 | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1598255 | Inhibition of recombinant human His6-tagged PDE4D UCR2 deletion mutant catalytic domain expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yea | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID1598238 | Inhibition of recombinant human His6-tagged PDE4D7 UCR1 S129D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruva | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID1598953 | Protection against imiquimod-induced skin inflammation in BALB/c mouse psoriasis model assessed as decrease in skin scaling at 25 mg/kg, po administered once daily for 7 days | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1598195 | Inhibition of recombinant human His6-tagged PDE4B1 UCR1 S133D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruva | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID395575 | Inhibition of TNFalpha production in LPS-stimulated human whole blood preincubated before LPS challenge measured after 4 hrs by enzyme immunoassay | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1720007 | Inhibition of PDE4 (unknown origin) | 2020 | Journal of medicinal chemistry, 10-08, Volume: 63, Issue:19 | Advances in the Development of Phosphodiesterase-4 Inhibitors. |
| AID1598952 | Protection against imiquimod-induced skin inflammation in BALB/c mouse psoriasis model assessed as decrease in lesion thickness at 25 mg/kg, po administered once daily for 7 days | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1598955 | Protection against imiquimod-induced skin inflammation in BALB/c mouse psoriasis model assessed as decrease in cumulative psoriasis score at 25 mg/kg, po administered once daily for 7 days | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID395580 | Inhibition of CYP2D6 | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1713827 | Inhibition of human PDE4B using [3H]cAMP as substrate at 100 nM incubated for 5 mins followed by substrate addition and measured after 10 mins by scintillation proximity assay relative to control | 2016 | Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22 | In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors. |
| AID393501 | Antiinflammatory activity in rat assessed as inhibition of LPS-induced TNFalpha production at 0.01 mg/kg, po | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1596278 | Inhibition of PDE4B (unknown origin) | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID393494 | Half life in rat at 5 mg/kg, iv | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID393503 | Antiinflammatory activity in po dosed rat assessed as inhibition of LPS-induced neutrophilia in bronchoalveolar lavage fluid | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1598196 | Inhibition of recombinant human His6-tagged PDE4D7 UCR1 S129D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruva | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID393495 | Clearance in rat at 5 mg/kg, iv | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID393496 | Volume of distribution at steady state in rat at 5 mg/kg, iv | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1455744 | Inhibition of recombinant human PDE4B2 expressed in African green monkey COS7 cells using cAMP as substrate | 2018 | Journal of medicinal chemistry, 03-22, Volume: 61, Issue:6 | 4-Amino-7,8-dihydro-1,6-naphthyridin-5(6 H)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure-Activity Relationships. |
| AID1598959 | Inhibition of PDE4D (unknown origin) using cAMP as substrate | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID395574 | Inhibition of TNFalpha production in LPS-stimulated human PBMC preincubated before LPS challenge measured after 4 hrs by enzyme immunoassay | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1598239 | Inhibition of recombinant human wild-type His6-tagged PDE4D7 UCR1 domain (S129 residues) expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by ye | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID393499 | Half life in rat at 10 mg/kg, po | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1598954 | Protection against imiquimod-induced skin inflammation in BALB/c mouse psoriasis model assessed as decrease in skin erythema at 25 mg/kg, po administered once daily for 7 days | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1713829 | Inhibition of PDE-4 in human PBMC assessed as LPS-induced TNFalpha production at 1000 nM incubated for 15 mins followed by LPS stimulation and measured after 18 hrs by ELISA relative to control | 2016 | Bioorganic & medicinal chemistry, 11-15, Volume: 24, Issue:22 | In vivo effective dibenzo[b,d]furan-1-yl-thiazoles as novel PDE-4 inhibitors. |
| AID1596298 | Inhibition of recombinant N-terminal GST tagged human PDE4A4B (2-end aa) expressed in Sf9 cells using FAM-cAMP as substrate at 1xIC50 incubated for 60 mins by fluorescence plate reader analysis | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID1651548 | Inhibition of human PDE4D catalytic domain (86 to 413 residues) expressed in Escherichia coli BL21 (DE3) cells using [3H]cAMP as substrate measured after 30 mins by scintillation proximity assay | 2020 | Journal of natural products, 04-24, Volume: 83, Issue:4 | Diterpenoids from the Root Bark of |
| AID1596275 | Inhibition of recombinant N-terminal GST-tagged full length human PDE4A1A expressed in Sf9 cells using cAMP as substrate at 0.1xIC50 incubated for 60 mins by fluorescence plate reader analysis | 2019 | European journal of medicinal chemistry, Jul-15, Volume: 174 | InCl |
| AID1598908 | Fraction absorbed in human Caco2 cells measured after 95 mins by LC-MS/MS analysis | 2019 | Journal of medicinal chemistry, 06-13, Volume: 62, Issue:11 | Structure-Aided Identification and Optimization of Tetrahydro-isoquinolines as Novel PDE4 Inhibitors Leading to Discovery of an Effective Antipsoriasis Agent. |
| AID1598254 | Inhibition of recombinant human His6-tagged PDE4D UCR2 deletion mutant catalytic domain expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yea | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID1598240 | Inhibition of recombinant human His6-tagged PDE4B1 UCR1 S133D mutant expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruva | 2019 | Journal of medicinal chemistry, 05-23, Volume: 62, Issue:10 | Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders. |
| AID393498 | AUC in rat at 10 mg/kg, po | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID395577 | Inhibition of CYP1A2 | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID395576 | Metabolic stability in human microsomes assessed as half life | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID395584 | AUC in rat at 5 mg/kg, iv | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID393502 | Antiinflammatory activity in po dosed rat assessed as inhibition of LPS-induced TNFalpha production | 2009 | Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6 | Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. |
| AID1345234 | Human phosphodiesterase 4B (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) | 2014 | Cellular signalling, Sep, Volume: 26, Issue:9 | Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. |
| AID1345281 | Human phosphodiesterase 4C (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) | 2014 | Cellular signalling, Sep, Volume: 26, Issue:9 | Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. |
| AID1345251 | Human phosphodiesterase 4A (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) | 2014 | Cellular signalling, Sep, Volume: 26, Issue:9 | Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. |
| AID1345239 | Human phosphodiesterase 4D (Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs)) | 2014 | Cellular signalling, Sep, Volume: 26, Issue:9 | Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 4 (0.68) | 29.6817 |
| 2010's | 284 (47.97) | 24.3611 |
| 2020's | 304 (51.35) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.
| This Compound (79.89) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 96 (15.51%) | 5.53% |
| Reviews | 126 (20.36%) | 6.00% |
| Case Studies | 92 (14.86%) | 4.05% |
| Observational | 20 (3.23%) | 0.25% |
| Other | 285 (46.04%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| An Investigator Initiated Study of Monocyte Biomarkers in Moderate to Severe Plaque Psoriasis Subjects Treated With Apremilast [NCT03442088] | Phase 2 | 28 participants (Actual) | Interventional | 2018-06-01 | Completed | ||
| Expanded Access for CC-10004 [NCT03740516] | 0 participants | Expanded Access | No longer available | ||||
| A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double Blind-Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Genital Psoriasis [NCT03777436] | Phase 3 | 289 participants (Actual) | Interventional | 2019-02-11 | Completed | ||
| Open-Label Study to Assess the Safety and Efficacy of Apremilast in Patients With Chronic Plaque Psoriasis Who Have Failed One Course of Biologic Therapy. [NCT01200264] | Phase 2 | 0 participants (Actual) | Interventional | 2010-09-30 | Withdrawn(stopped due to Contract never executed; withdrawn by sponsor) | ||
| Apremilast in Combination With Clobetasol Spray for the Treatment of Plaque Psoriasis [NCT03453190] | Phase 4 | 20 participants (Anticipated) | Interventional | 2018-02-25 | Recruiting | ||
| A Phase 3, Multi-Center, Randomized, Placebo-Controlled, Double-Blind, Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis of the Scalp [NCT03123471] | Phase 3 | 303 participants (Actual) | Interventional | 2017-05-16 | Completed | ||
| A Phase 3b, Open-label, Single-arm Study of the Efficacy and Safety of Apremilast, in Subjects With Plaque Psoriasis That is Not Adequately Controlled by Topical Therapy [NCT03930186] | Phase 3 | 152 participants (Actual) | Interventional | 2019-06-17 | Completed | ||
| Medication Development for Protracted Abstinence in Alcoholism: Apremilast Versus Placebo [NCT03175549] | Phase 2 | 51 participants (Actual) | Interventional | 2017-11-01 | Completed | ||
| A Phase 4, Multicenter, Randomized, Placebo-controlled, Double-blind, Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate Plaque Psoriasis [NCT02425826] | Phase 4 | 221 participants (Actual) | Interventional | 2015-04-20 | Completed | ||
| An Open-label Pilot Study to Investigate the Efficacy of Apremilast in the Treatment of Central Centrifugal Cicatricial Alopecia (CCCA) [NCT03521687] | Phase 4 | 20 participants (Actual) | Interventional | 2018-11-15 | Completed | ||
| A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis Who Have Not Been Previously Treated With Disease-modifying A [NCT01307423] | Phase 3 | 529 participants (Actual) | Interventional | 2010-12-09 | Completed | ||
| A Phase IV, Open Label Study of the Effects of Apremilast on Vascular Inflammation and Cardiometabolic Function in Psoriasis [NCT03082729] | Phase 4 | 70 participants (Actual) | Interventional | 2017-04-24 | Completed | ||
| The Controlled Trial of Apremilast for Rheumatoid Arthritis Treatment [NCT01250548] | Phase 2 | 34 participants (Actual) | Interventional | 2010-05-31 | Completed | ||
| A Phase 2, Multicenter, Randomized, Doubleblind, Placebo-controlled, Parallel-group,Efficacy Study of Apremilast (CC-10004)in Subjects With Erosive Hand Osteoarthritis [NCT01200472] | Phase 2 | 30 participants (Actual) | Interventional | 2010-08-31 | Completed | ||
| Concomitant Use of Apremilast for the Treatment of Active RA Despite TNF-Inhibition and Methotrexate- CATARA [NCT01204138] | Phase 2 | 0 participants (Actual) | Interventional | 2010-09-30 | Withdrawn(stopped due to decision of sponsor to withdraw before initiation; 0 patients enrolled) | ||
| A Prospective, Randomized, Controlled, Open Label, Assessor-blinded, Parallel-group Phase III Clinical Trial to Evaluate the Impact of Tapering Systemic Immunosuppressive Therapy in a Treat-to-target Approach on Maintaining Minimal Disease Activity in Adu [NCT04610476] | Phase 3 | 270 participants (Anticipated) | Interventional | 2020-10-19 | Recruiting | ||
| A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Palmoplantar Pustulosis in Japan [NCT04057937] | Phase 2 | 90 participants (Actual) | Interventional | 2019-10-16 | Completed | ||
| Observational Study on Quality of Life and Ultrasonographic Assessment of Nail Psoriasis After Treatment With Apremilast (JUST Study) [NCT03616561] | 45 participants (Actual) | Observational | 2018-02-23 | Completed | |||
| A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Early, Oligoarticular Psoriatic Arthritis Despite Initial Stable Treatment With Either [NCT03747939] | Phase 4 | 310 participants (Actual) | Interventional | 2018-12-31 | Completed | ||
| I-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients [NCT04488081] | Phase 2 | 1,500 participants (Anticipated) | Interventional | 2020-07-31 | Recruiting | ||
| A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN PEDIATRIC SUBJECTS FROM 6 THROUGH 17 YEARS WITH MODERATE TO SEVERE PLAQUE PSORIASIS [NCT03701763] | Phase 3 | 245 participants (Actual) | Interventional | 2018-12-19 | Terminated(stopped due to PPSO-003 (20200056) is closing: - Last Subject Enrolled was 30-Dec-2021 - The Recruitment Status has to be updated to Terminated. LSLV was achieved 27-Mar-2023) | ||
| Preliminary Efficacy and Safety of Apremilast in the Treatment of Acne Conglobata: A Phase II, Single Centre, Open Label, Proof of Concept Study for the Treatment of Acne Conglobata With the PDE-4 Inhibitor Apremilast (APACCO-Study) [NCT04161456] | Phase 2 | 1 participants (Actual) | Interventional | 2019-10-09 | Completed | ||
| Adherence to Otezla in Patients With Mild Psoriasis [NCT05601492] | Early Phase 1 | 84 participants (Anticipated) | Interventional | 2023-12-31 | Not yet recruiting | ||
| A Phase 1, Open-label, Two Part Study to Evaluate the Pharmacokinetics of Single and Multiple Doses of Apremilast in Healthy Adult Male Korean Subjects [NCT02802735] | Phase 1 | 28 participants (Actual) | Interventional | 2016-06-22 | Completed | ||
| A Multicenter, Open Label, Single-arm Pilot Study to Evaluate the Efficacy and Safety of Oral Apremilast in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP) (APLANTUS) [NCT04572997] | Phase 2 | 21 participants (Actual) | Interventional | 2018-11-29 | Completed | ||
| A Split Body Study of the Effects of Combined Therapy With Narrow-Band Ultraviolet B Phototherapy and Apremilast for the Treatment of Vitiligo [NCT03123016] | Phase 2 | 23 participants (Actual) | Interventional | 2017-04-14 | Completed | ||
| Clinical and Immune-modulating Effects of CC-10004 in Discoid Lupus Erythematosus [NCT00708916] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2008-06-30 | Completed | ||
| Real World Study on the Efficacy and Safety of Apremilast in Chinese Patients With Moderate to Severe Plaque Psoriasis, a Multi Center, Prospective, Observational Trial（REACT） [NCT05863273] | 360 participants (Anticipated) | Observational | 2023-05-20 | Not yet recruiting | |||
| Observational Study Evaluating the Real-World Effectiveness, Safety and Tolerability of Treatment With Apremilast in Psoriatic Arthritis Patients Followed in Canadian Routine Care (APPRAISE) [NCT03608657] | 102 participants (Actual) | Observational | 2018-07-31 | Completed | |||
| An Open-label, Single-arm Pilot Study of the Safety and Efficacy of an Oral PDE4-inhibitor Agent, Apremilast, in the Treatment of Moderate to Severe Acne [NCT01074502] | Phase 2 | 3 participants (Actual) | Interventional | 2010-02-28 | Terminated(stopped due to lack of funding due to Celgene administrative decision) | ||
| A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis [NCT01232283] | Phase 3 | 413 participants (Actual) | Interventional | 2010-11-22 | Completed | ||
| Open-Label, Single-Arm Pilot Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety, and Preliminary Efficacy of CC10004 in Subjects With Severe Plaque Type Psoriasis [NCT00604682] | Phase 2 | 19 participants (Actual) | Interventional | 2005-01-01 | Completed | ||
| Randomized Double Blind Controlled Trial Comparing the Safety and Efficacy of Apremilast Versus Placebo in Severe Forms of Recurrent Aphthous Stomatitis [NCT04227314] | Phase 3 | 134 participants (Anticipated) | Interventional | 2022-01-31 | Not yet recruiting | ||
| Apremilast as Anti-pruritic Treatment in Patients With Prurigo Nodularis [NCT03576287] | Phase 1/Phase 2 | 15 participants (Anticipated) | Interventional | 2017-07-01 | Recruiting | ||
| A Phase 4 Multicenter, Randomized, Placebo-controlled Study Evaluating the Effect of Apremilast on Pruritus and Quality of Life of Patients With Moderate-to-severe Scalp Psoriasis [NCT03553433] | Phase 4 | 90 participants (Anticipated) | Interventional | 2018-06-30 | Not yet recruiting | ||
| A Phase 2, Multicenter, Open-Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Apremilast (CC-10004) in Pediatric Subjects With Moderate to Severe Plaque Psoriasis [NCT02576678] | Phase 2 | 42 participants (Actual) | Interventional | 2015-10-13 | Completed | ||
| Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia [NCT02735707] | Phase 3 | 10,000 participants (Anticipated) | Interventional | 2016-04-11 | Recruiting | ||
| A Phase 2 Open-label Single Center Study to Evaluate the Efficacy of Apremilast for the Treatment of Moderate Hidradenitis Suppurativa [NCT02695212] | Phase 2 | 20 participants (Actual) | Interventional | 2016-07-31 | Completed | ||
| Validation of the PsASon ULtrasound Scores in Patients With Psoriatic Arthritis Undergoing TReatment With Apremilast [NCT04102449] | Phase 4 | 0 participants (Actual) | Interventional | 2020-07-01 | Withdrawn(stopped due to Funding stopped) | ||
| An Open-label Trial to Assess the Efficacy and Safety of Apremilast in the Management of Vision-threatening Uveitis That is Refractory to Other Modes of Systemic Immunosuppression. [NCT00889421] | Phase 1/Phase 2 | 3 participants (Actual) | Interventional | 2009-11-30 | Terminated(stopped due to Investigator discretion due to lack of efficacy in three subjects enrolled) | ||
| A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis [NCT01194219] | Phase 3 | 844 participants (Actual) | Interventional | 2010-09-09 | Completed | ||
| The AP-GELP Study: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Phosphodiesterase 4-Inhibitor Apremilast in Female Genital Erosive Lichen Planus [NCT03656666] | Phase 2 | 42 participants (Anticipated) | Interventional | 2019-09-24 | Active, not recruiting | ||
| [NCT03022617] | Phase 4 | 12 participants (Actual) | Interventional | 2017-01-31 | Completed | ||
| A Phase 1, Open Label, Randomized, Two Part Study to Evaluate the Pharmacokinetic Exposure of a Once-Daily (QD) Apremilast Formulation Relative to the Twice-Daily (BID) Reference Immediate Release (IR) Tablet and the Effect of Food on the QD Apremilast Fo [NCT02777554] | Phase 1 | 144 participants (Actual) | Interventional | 2016-08-17 | Completed | ||
| Prevalence, Pattern and Disease Course og Arthritis and Enthesitis in Patients With Psoriasis, and Effect of Apremilast in Subclinical, US-defined Psoriatic Arthritis - a Population Based Study Applying Clinical, Ultrasonic, MRI and Patient-reported Outco [NCT04515732] | Phase 4 | 115 participants (Anticipated) | Interventional | 2018-12-14 | Enrolling by invitation | ||
| A Phase 3 Randomized, Double-Blind, Placebo- and Active-Controlled Study of the Efficacy and Safety of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Plaque Psoriasis [NCT03168256] | Phase 3 | 528 participants (Actual) | Interventional | 2018-09-15 | Completed | ||
| A Clinical Trial Of CC-10004 For The Treatment Of Vulvodynia [NCT00814632] | Phase 2 | 10 participants (Actual) | Interventional | 2008-12-31 | Completed | ||
| DARWIN: Description of Apremilast Real World Italian Psoriasis Network - a Multicenter, Observational, Cross-sectional Study to Describe Patient Characteristics and Treatment Pattern [NCT04031027] | 184 participants (Actual) | Observational | 2019-07-22 | Completed | |||
| A Skin and Synovial Tissue Assessment of Overlapping Genes and Their Response After 3 Months Treatment With Apremilast in Patients With Psoriatic Arthritis [NCT02558361] | Phase 4 | 0 participants (Actual) | Interventional | 2016-04-30 | Withdrawn(stopped due to FDA approved synovial biopsy device unavailable) | ||
| A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis and a Qualifying Psoriasis Lesion [NCT01212770] | Phase 3 | 505 participants (Actual) | Interventional | 2010-09-30 | Completed | ||
| An Observational Study of the Real-life Management of Psoriatic Arthritis Patients Treated With Otezla® (Apremilast) in Belgium [NCT03096990] | 106 participants (Actual) | Observational | 2017-04-21 | Completed | |||
| An Open-Label Pilot Study to Evaluate the Safety and Efficacy of Apremilast (CC-10004) in the Treatment of Moderate to Severe Lichen Planus [NCT01041625] | Phase 2 | 10 participants (Anticipated) | Interventional | 2010-02-28 | Not yet recruiting | ||
| An Open Label, Single Center Study to Assess the Safety and Efficacy of a 24 Week Treatment Course of CC-10004 in Adults With Recalcitrant Nodularis [NCT00869089] | Phase 2 | 5 participants (Actual) | Interventional | 2008-09-30 | Completed | ||
| An Open Label Study Evaluating the Safety and Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Dermatomyositis [NCT01140503] | 5 participants (Actual) | Interventional | 2010-02-28 | Terminated(stopped due to Slow recruitment of participants) | |||
| A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Followed by an Active-Treatment Extension to Evaluate the Efficacy and Safety of Apremilast(CC-10004) in the Treatment of Behçet Disease [NCT00866359] | Phase 2 | 111 participants (Actual) | Interventional | 2009-08-01 | Completed | ||
| A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis [NCT01212757] | Phase 3 | 488 participants (Actual) | Interventional | 2010-09-27 | Completed | ||
| Apremilast Therapy for Acute Gouty Arthritis [NCT00997581] | Phase 2 | 0 participants (Actual) | Interventional | 2010-04-30 | Withdrawn(stopped due to Colaborator withdrew support.) | ||
| A Phase 2, Open Label Single Arm Study for Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis [NCT03529955] | Phase 2 | 8 participants (Actual) | Interventional | 2018-06-12 | Completed | ||
| Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004)in the Treatment of Ankylosing Spondylitis (AS) [NCT00944658] | Phase 2 | 38 participants (Actual) | Interventional | 2009-08-31 | Completed | ||
| A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose Comparison Study of CC-10004 in Subjects With Moderate-to-Severe Plaque-Type Psoriasis [NCT00606450] | Phase 2 | 260 participants (Actual) | Interventional | 2006-04-01 | Completed | ||
| A Phase 3, Multicenter, Open-label, Long-term Extension Study of Apremilast in Children 2 Years of Age or Older With Oral Ulcers Associated With Behçet's Disease or 5 Years of Age or Older With Juvenile Psoriatic Arthritis [NCT05767047] | Phase 3 | 48 participants (Anticipated) | Interventional | 2023-03-23 | Recruiting | ||
| A Multi-Center, Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Phase 3 Study With Randomized Withdrawal and Retreatment to Evaluate the Efficacy and Safety of BMS-986165 in Subjects With Moderate-to-Severe Plaque Psoriasis [NCT03611751] | Phase 3 | 1,020 participants (Actual) | Interventional | 2018-07-26 | Completed | ||
| A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Dose Regimens of CC-10004 in Subjects With Active Psoriatic Arthritis [NCT00456092] | Phase 2 | 204 participants (Actual) | Interventional | 2007-03-05 | Completed | ||
| A Phase 2, Open-label Multi-center Study to Evaluate the Safety, Pharmacodynamics, Pharmacokinetics, and Efficacy of Apremilast in Subjects With Recalcitrant Plaque-type Psoriasis [NCT00521339] | Phase 2 | 31 participants (Actual) | Interventional | 2007-08-01 | Completed | ||
| A Phase 3, Randomized, Multicenter, Double-Blind, Placebo- and Active Comparator-Controlled Study With a Randomized Withdrawal and Retreatment Period to Evaluate the Efficacy, Safety, and Tolerability of TAK-279 in Subjects With Moderate-to-Severe Plaque [NCT06108544] | Phase 3 | 1,000 participants (Anticipated) | Interventional | 2023-11-06 | Recruiting | ||
| A Phase 3, Randomized, Multicenter, Double-Blind, Placebo- and Active Comparator-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-279 in Subjects With Moderate-to-Severe Plaque Psoriasis [NCT06088043] | Phase 3 | 600 participants (Anticipated) | Interventional | 2023-11-06 | Recruiting | ||
| An Open Label, Balanced, Randomized, Two-treatment, Two-period, Two-sequence, Single Oral Dose, Cross Over Bioequivalence Study of Two Products of Apremilast 30 mg Tablets in Normal, Healthy, Adult, Human Subjects Under Fasting Condition [NCT06084663] | Phase 3 | 36 participants (Actual) | Interventional | 2023-02-15 | Completed | ||
| A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Apremilast (AMG 407) in Japanese Subjects With Palmoplantar Pustulosis (PPP) [NCT05174065] | Phase 3 | 176 participants (Actual) | Interventional | 2022-03-08 | Active, not recruiting | ||
| Apremilast for the Treatment of Refractory Erythema Multiforme [NCT05875714] | Phase 2 | 8 participants (Anticipated) | Interventional | 2022-01-13 | Recruiting | ||
| A Multi-center, Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Deucravacitinib in Participants With Active Psoriatic Arthritis (PsA) Who Are Naïve to Biologic Disease Modifying Anti-rheumatic Drugs or Had [NCT04908189] | Phase 3 | 700 participants (Anticipated) | Interventional | 2021-07-15 | Active, not recruiting | ||
| Efficacy of Oral Apremilast in the Treatment of Alopecia Areata at the Tertiary Care Hospital, Karachi. [NCT05926882] | Phase 4 | 30 participants (Actual) | Interventional | 2022-08-01 | Completed | ||
| A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study, To Compare the Efficacy and Safety of Two Doses of Apremilast (CC-10004) in Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methot [NCT01285310] | Phase 2 | 237 participants (Actual) | Interventional | 2010-12-09 | Terminated(stopped due to Study is terminated due to lack of efficacy) | ||
| An Open-label, Single-Arm Pilot Study Investigating the Efficacy and Safety of Apremilast for the Treatment of Moderate to Severe Chronic Hand Dermatitis [NCT03741933] | Phase 4 | 0 participants (Actual) | Interventional | 2019-02-28 | Withdrawn(stopped due to The principal investigator left George Washington University and closed the study at their departure.) | ||
| The Maintenance Effect of Enstilar Foam in Combination With Otezla [NCT04555707] | Phase 4 | 30 participants (Anticipated) | Interventional | 2020-06-24 | Recruiting | ||
| A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis [NCT01172938] | Phase 3 | 504 participants (Actual) | Interventional | 2010-06-02 | Completed | ||
| A Phase 4 Multicenter, Randomized, Open-label, Efficacy Assessor-blinded Study of Risankizumab Compared to Apremilast for the Treatment of Adult Subjects With Moderate Plaque Psoriasis Who Are Candidates for Systemic Therapy [NCT04908475] | Phase 3 | 352 participants (Actual) | Interventional | 2021-06-09 | Completed | ||
| A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Mild to Moderate Plaque Psoriasis [NCT03721172] | Phase 3 | 595 participants (Actual) | Interventional | 2019-03-11 | Completed | ||
| A Phase 3, Multi-center, Open-label, Single-arm Study to Assess the Safety of Apremilast (AMG 407) in Pediatric Participants From 6 Through 17 Years of Age With Mild to Moderate Plaque Psoriasis [NCT06088199] | Phase 3 | 50 participants (Anticipated) | Interventional | 2023-10-24 | Recruiting | ||
| A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate-to-Severe Plaque-Type Psoriasis (Core Study) [NCT00773734] | Phase 2 | 352 participants (Actual) | Interventional | 2008-09-01 | Completed | ||
| Effects of Treatment With Biological Agents on Endothelial Glycocalyx,Arterial Elastic Properties, Coronary Flow, Myocardial Deformation and Twisting in Psoriasis. Comparative Study With Patients With CAD or Untreated Hypertension. [NCT02144857] | Phase 4 | 200 participants (Anticipated) | Interventional | 2014-05-30 | Recruiting | ||
| An Open Label Study of Apremilast in Chronic Idiopathic Pruritus [NCT03239106] | Phase 2 | 10 participants (Actual) | Interventional | 2017-12-01 | Completed | ||
| A Pilot Study Evaluating the Efficacy of Apremilast in the Treatment of Subjects With Severe Recurrent Aphthous Stomatitis (RAS) [NCT03690544] | Phase 4 | 15 participants (Actual) | Interventional | 2018-10-12 | Completed | ||
| A Phase 4, Multicenter, Single-Arm, Open-Label Study to Evaluate the Impact of Apremilast (CC-10004) on MRI Outcomes in Subjects With Active Psoriatic Arthritis [NCT03783026] | Phase 4 | 123 participants (Actual) | Interventional | 2019-02-06 | Completed | ||
| A Phase 2, Open-label, Investigator-Initiated Study to Evaluate the Safety and Efficacy of Apremilast in Subjects With Recalcitrant Contact or Atopic Dermatitis [NCT00931242] | Phase 2 | 10 participants (Actual) | Interventional | 2009-06-30 | Completed | ||
| Apremilast Pregnancy Exposure Registry OTIS Autoimmune Diseases in Pregnancy Project [NCT02775500] | 233 participants (Actual) | Observational [Patient Registry] | 2014-11-30 | Active, not recruiting | |||
| A Pilot Study to Evaluate the Efficacy and Safety of Apremilast in Patients of Chronic and Recurrent Erythema Nodosum Leprosum [NCT04822909] | Phase 4 | 10 participants (Actual) | Interventional | 2019-09-15 | Completed | ||
| A 2-Part, Safety, Tolerability, and Pharmacokinetic Study of LY2775240 in Healthy Subjects [NCT02963779] | Phase 1 | 35 participants (Actual) | Interventional | 2016-12-31 | Completed | ||
| A Phase 2, Randomized, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Apremilast (CC-10004) for Treatment of Subjects With Active Ulcerative Colitis [NCT02289417] | Phase 2 | 170 participants (Actual) | Interventional | 2015-01-08 | Completed | ||
| Bioequivalence of Three Different Tablet Formulations of 30 mg of Apremilast (EU-sourced Otezla® vs. US-sourced Otezla® vs. Japan-sourced Otezla®) Administered in Healthy Male and Female Subjects in the Fasted State as Well as (for EU-sourced Otezla® vs. [NCT04811573] | Phase 1 | 20 participants (Actual) | Interventional | 2021-03-31 | Terminated(stopped due to due to company decision) | ||
| Industry Alliance Platform Trial to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients [NCT04590586] | Phase 3 | 515 participants (Actual) | Interventional | 2020-11-24 | Completed | ||
| Efficacy and Safety of Apremilast in Patients With Moderate to Severe Chronic Plaque Psoriasis [NCT06032858] | Phase 4 | 30 participants (Actual) | Interventional | 2022-03-06 | Completed | ||
| A Phase 1, Open-Label, Randomized Three-Period, Six-Sequence Crossover Study In Healthy Adult Subjects To Evaluate The Bioavailablity Of An Oral Suspension Formulation Relative To The Tablet Formulation Of Apremilast And To Assess The Effect Of Food On Th [NCT02641353] | Phase 1 | 34 participants (Actual) | Interventional | 2016-01-05 | Completed | ||
| Apremilast 30 mg BID Combined With Dupilumab for the Treatment of Recalcitrant Moderate-to-Severe Atopic Dermatitis [NCT04306965] | Phase 2 | 20 participants (Anticipated) | Interventional | 2020-08-01 | Recruiting | ||
| Use of Apremilast in Patients Who Are Dissatisfied With Stable Maintenance Topical Therapy [NCT03000309] | Phase 4 | 20 participants (Actual) | Interventional | 2016-12-29 | Completed | ||
| An Open-Label, Single-Dose Study to Evaluate the Effects of Age and Sex on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Subjects [NCT01634191] | Phase 1 | 36 participants (Actual) | Interventional | 2012-02-01 | Completed | ||
| Assessment of the Clinical and Ultrasound Response to Apremilast by Clinical Evaluation and by a Joint-periarticular-nail Ultrasound Index in Patients With Active Psoriatic Arthritis [NCT03191539] | Phase 3 | 56 participants (Anticipated) | Interventional | 2017-11-02 | Not yet recruiting | ||
| Routine Clinical Practice in Spain: Evaluation of the Use of Apremilast in Patients With Psoriatic Arthritis, Naïve to Biological Treatment (PREVAIL Study) [NCT03828045] | 119 participants (Actual) | Observational | 2019-02-06 | Completed | |||
| An Open Label, Pilot Study to Determine the Efficacy of Apremilast in the Treatment of Rosacea in Patients With Both Erythematotelangiectatic Rosacea and Papulopustular Rosacea [NCT01045551] | Phase 2 | 10 participants (Actual) | Interventional | 2010-06-30 | Completed | ||
| A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Apremilast in Children From 5 to Less Than 18 Years of Age With Active Juvenile Psoriatic Arthritis (PEAPOD [NCT04804553] | Phase 3 | 60 participants (Anticipated) | Interventional | 2022-03-17 | Recruiting | ||
| Short-term Safety, Efficacy and Mode of Action of Apremilast in Moderate Suppurative Hidradenitis: A Randomised Double-blind Placebo Controlled Trial [NCT03049267] | Phase 2 | 20 participants (Actual) | Interventional | 2017-02-02 | Completed | ||
| A Phase 3, Multicenter, Randomized, Doubleblind, Placebo-controlled, Parallel Group Study, Followed by an Active-treatment Phase to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Subjects With Active Behcet's Disease [NCT02307513] | Phase 3 | 207 participants (Actual) | Interventional | 2014-12-30 | Completed | ||
| The APOLP Trial: A Single-Center, Randomized, 16 Weeks, Explanatory, Parallel-Group, Superiority, Blinded, Placebo-Controlled, Clinical Trial of Apremilast Use in Oral Lichen Planus [NCT03836885] | Phase 2 | 0 participants (Actual) | Interventional | 2019-11-21 | Withdrawn(stopped due to Study was terminated due to delay in enrollment.) | ||
| A Multi-Center, Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of BMS-986165 in Subjects With Moderate-to-Severe Plaque Psoriasis [NCT03624127] | Phase 3 | 666 participants (Actual) | Interventional | 2018-08-07 | Completed | ||
| Open Label Trial Evaluating the Efficacy of Apremilast for the Treatment of Frontal Fibrosing Alopecia [NCT03422640] | Phase 4 | 20 participants (Anticipated) | Interventional | 2018-07-12 | Recruiting | ||
| Real-world Benefit of Apremilast Treatment of Patients With Moderate-to-severe Psoriasis After Transition From Fumaric Acid Esters [NCT02954081] | 687 participants (Actual) | Observational | 2017-01-26 | Completed | |||
| A Double-blind, Placebo-controlled, Randomized Study on the Safety and Efficacy of Apremilast in Patients With Moderate to Severe Plaque Psoriasis Involving Palms and/or Soles [NCT02400749] | Phase 4 | 100 participants (Actual) | Interventional | 2015-05-31 | Completed | ||
| Efficacy and Safety of Combining Apremilast 30mg Bid With Narrowband UVB in the Treatment of Moderate-to-severe Plaque Psoriasis [NCT02412644] | Phase 4 | 29 participants (Actual) | Interventional | 2015-05-28 | Completed | ||
| A Phase 1, Open-Label, Randomized, Two-Period, Two-Sequence Crossover Study to Assess the Effect of Food on the Pharmacokinetics of a Single 30 mg Tablet of Apremilast (CC-10004) in Healthy Subjects [NCT01634178] | Phase 1 | 46 participants (Actual) | Interventional | 2012-02-01 | Completed | ||
| A Phase 1, Open-label, Three-period, Fixed-sequence Study to Evaluate the Effects of Rifampin on the Pharmacokinetics of Apremilast (CC-10004) in Healthy Subjects [NCT01561963] | Phase 1 | 21 participants (Actual) | Interventional | 2012-02-01 | Completed | ||
| An Investigator-initiated, Randomized, Double-blind, Placebo Controlled Study of Apremilast to Demonstrate Efficacy in Subjects With Nummular Eczema [NCT03160248] | Phase 2 | 31 participants (Actual) | Interventional | 2017-07-05 | Completed | ||
| Immune Metabolic Associations in Psoriatic Arthritis Study [NCT03399708] | 60 participants (Actual) | Observational | 2017-06-12 | Completed | |||
| A Randomized Placebo-controlled Single Center Pilot Study of the Safety and Efficacy of Apremilast in Subjects With Moderate to Severe Alopecia Areata [NCT02684123] | 30 participants (Actual) | Interventional | 2016-02-29 | Completed | |||
| A Single Center Study to Evaluate the Effectiveness and Safety of Add on Enstilar® in Patients Using OTEZLA® for Moderate to Severe Plaque Psoriasis [NCT03587194] | Phase 4 | 50 participants (Anticipated) | Interventional | 2018-07-23 | Recruiting | ||
| A Phase 3B, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Double-Dummy, Study Of The Efficacy And Safety Of Apremilast (CC-10004), Etanercept, And Placebo, In Subjects With Moderate To Severe Plaque Psoriasis [NCT01690299] | Phase 3 | 250 participants (Actual) | Interventional | 2012-10-01 | Completed | ||
| Repigmentation Using Apremilast and Phototherapy In Diffuse VITILIGO RAPID VITILIGO [NCT03036995] | Phase 2 | 80 participants (Actual) | Interventional | 2017-03-20 | Completed | ||
| An Observational Study of the Real-life Management of Psoriasis Patients Treated With Otezla® (Apremilast) in Belgium [NCT03097003] | 124 participants (Actual) | Observational | 2017-04-06 | Completed | |||
| A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of Apremilast 30 mg Twice Daily in Chinese Subjects With Moderate to Severe Plaque-type Psoriasis [NCT06122649] | Phase 3 | 200 participants (Anticipated) | Interventional | 2023-11-27 | Recruiting | ||
| A Phase 3, Multicenter, Open-label, Single-arm Study to Assess the Efficacy and Safety of Apremilast (AMG 407) in Japanese Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis [NCT05565560] | Phase 3 | 33 participants (Anticipated) | Interventional | 2023-01-25 | Recruiting | ||
| A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study, Followed by an Active Treatment Phase to Evaluate the Efficacy and Safety of Apremilast in Children From 2 to Less Than 18 Years of Age With Active Oral Ulcers Ass [NCT04528082] | Phase 3 | 60 participants (Anticipated) | Interventional | 2021-09-09 | Recruiting | ||
| A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) Monotherapy in Subjects With Active Psoriatic Arthritis [NCT01925768] | Phase 3 | 219 participants (Actual) | Interventional | 2013-09-04 | Completed | ||
| A Pilot Study of an Oral Phosphodiesterase Inhibitor (Apremilast) for Atopic Dermatitis in Adults [NCT01393158] | Phase 2 | 16 participants (Actual) | Interventional | 2009-05-31 | Completed | ||
| Analysis of the Pathogenesis of Itch in Response to Apremilast Therapy in Psoriasis Patients [NCT03146247] | Phase 4 | 0 participants (Actual) | Interventional | 2017-10-23 | Withdrawn(stopped due to recruitment was not started) | ||
| Real Life Data for Otezla Evidence: Assessing Benefits of Apremilast in Patients With Moderate to Severe Chronic Plaque Psoriasis Followed by Dermatologists Under Real Life Settings in France [NCT03757013] | 453 participants (Actual) | Observational | 2018-09-25 | Completed | |||
| An Open-Label Study of CC-10004 for Chronic Prostatitis/Chronic Pelvic Pain Syndrome [NCT00701311] | Phase 2 | 21 participants (Actual) | Interventional | 2008-06-30 | Completed | ||
| A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Atopic Dermatitis [NCT02087943] | Phase 2 | 191 participants (Actual) | Interventional | 2014-06-30 | Completed | ||
| A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Subjects With Moderate-To-Severe Plaque-Type Psoriasis [NCT01988103] | Phase 2 | 254 participants (Actual) | Interventional | 2013-07-09 | Completed | ||
| A Phase 3b, Multi Center, Open-label, Long-term Extension Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis [NCT04175613] | Phase 3 | 160 participants (Actual) | Interventional | 2019-12-20 | Active, not recruiting | ||
| A Phase 1, Open-Label, Single Center Study to Evaluate the Pharmacokinetics of Prototype Modified-Release Formulations Of Apremilast (CC-10004) in Healthy Male Subjects [NCT02236988] | Phase 1 | 80 participants (Actual) | Interventional | 2014-01-07 | Completed | ||
| A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN THE TREATMENT OF ACTIVE ANKYLOSING SPONDYLITIS [NCT01583374] | Phase 3 | 490 participants (Actual) | Interventional | 2012-05-02 | Completed | ||
| A Phase 4, Multi-center, Randomized, Double-blind, Placebo-controlled Study of the Impact of Apremilast (CC-10004) on Quality of Life, Efficacy, and Safety in Subjects With Manifestations of Plaque Psoriasis and Impaired Quality of Life [NCT03774875] | Phase 4 | 277 participants (Actual) | Interventional | 2019-03-28 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28) + 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2 (NCT00456092)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 60.9 |
| Apremilast 20 mg BID | 67.5 |
| Placebo/Apremilast 40 mg QD | 65.0 |
| Placebo/Apremilast 20 mg BID | 55.0 |
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28) + 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2 (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 50.7 |
| Apremilast 20 mg BID | 44.9 |
| Placebo | 44.1 |
The DAS28-CRP(4) measures the severity of disease derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28-CRP(4) scores range from 0 to 9.4, where higher scores indicate more disease activity. Mild disease severity is defined as a DAS28-CRP(4) score of ≤ 3.2. In remission is defined as a DAS28-CRP(4) score of ≤ 2.6. (NCT00456092)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 38.8 |
| Apremilast 20 mg BID | 33.3 |
| Placebo | 23.5 |
The DAS28-CRP(3) measures the severity of disease derived from the following 3 variables: • 28 tender joint count (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) DAS28-CRP(3) scores range from 0 to 9.4, where higher scores indicate more disease activity. Mild disease severity is defined as a DAS28-CRP(3) score of ≤ 3.2. In remission is defined as a DAS28-CRP(3) score of ≤ 2.6. (NCT00456092)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 40.3 |
| Apremilast 20 mg BID | 34.8 |
| Placebo | 33.8 |
A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Participants with missing data were considered non-responders. (NCT00456092)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 26.1 |
| Apremilast 20 mg BID | 20.0 |
| Placebo/Apremilast 40 mg QD | 55.0 |
| Placebo/Apremilast 20 mg BID | 40.0 |
A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures, according to the following: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the patient global assessment of disease activity, measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Participants with no post-baseline PsARC scores were considered non-responders. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 50.7 |
| Apremilast 20 mg BID | 52.2 |
| Placebo | 22.1 |
A modified American College of Rheumatology 20% (ACR 20) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 35.8 |
| Apremilast 20 mg BID | 43.5 |
| Placebo | 11.8 |
A modified ACR 70 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Response at Week 24 was measured as improvement from Baseline (Day 1). Participants with no post-baseline ACR scores were considered non-responders. (NCT00456092)
Timeframe: Baseline (Day 1) and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 13.0 |
| Apremilast 20 mg BID | 17.5 |
| Placebo/Apremilast 40 mg QD | 15.0 |
| Placebo/Apremilast 20 mg BID | 5.0 |
A modified American College of Rheumatology 70% (ACR 70) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 7.5 |
| Apremilast 20 mg BID | 5.8 |
| Placebo | 1.5 |
A modified American College of Rheumatology 50% (ACR 50) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Participants with no post-baseline ACR scores were considered non-responders. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 13.4 |
| Apremilast 20 mg BID | 17.4 |
| Placebo | 2.9 |
The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: • percent improvement from Baseline in the 76 swollen joint count, • percent improvement from Baseline in the 78 tender joint count • median percent improvement from Baseline in the following 5 measures ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. The maximal ACR-N for each participant during the 12-week extension period was calculated, and represents the maximal ACR response achieved. (NCT00456092)
Timeframe: ACR was measured at Baseline and Weeks 16, 20 and 24
| Intervention | percent improvement (Mean) |
|---|---|
| Apremilast 40 mg QD | 29.1 |
| Apremilast 20 mg BID | 30.4 |
| Placebo/Apremilast 40 mg QD | 23.3 |
| Placebo/Apremilast 20 mg BID | 34.2 |
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein • Patient's global assessment of disease activity according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2 (NCT00456092)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 67.4 |
| Apremilast 20 mg BID | 60.0 |
| Placebo/Apremilast 40 mg QD | 70.0 |
| Placebo/Apremilast 20 mg BID | 50.0 |
The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Each question is answered on a scale from 0 (not at all) to 3 (very much). The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 40 mg QD | -2.6 |
| Apremilast 20 mg BID | -1.8 |
| Placebo | -0.3 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis). The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 40 mg QD | -0.9 |
| Apremilast 20 mg BID | -1.2 |
| Placebo | -0.2 |
"The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The total score ranges from 0 to 52 with higher scores representing less fatigue." (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 40 mg QD | 4.3 |
| Apremilast 20 mg BID | 4.1 |
| Placebo | 0.5 |
The number of participants who were dose reduced during the treatment phase due to adverse events. (NCT00456092)
Timeframe: Baseline to Week 12
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast 40 mg QD | 4 |
| Apremilast 20 mg BID | 4 |
| Placebo | 0 |
The number of participants who withdrew prematurely from the treatment phase due to lack of efficacy, including flare of psoriasis, flare of psoriatic arthritis or worsening or not responding to study treatment. (NCT00456092)
Timeframe: Baseline to Week 12
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast 40 mg QD | 0 |
| Apremilast 20 mg BID | 6 |
| Placebo | 12 |
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit. (NCT00456092)
Timeframe: 28-day observational follow-up period following Week 12
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast 40 mg QD | 5 |
| Apremilast 20 mg BID | 9 |
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase/Early Termination Visit. (NCT00456092)
Timeframe: Week 24 to Week 28 (28-day follow-up period)
| Intervention | participants (Number) |
|---|---|
| Apremilast 40 mg QD | 8 |
| Apremilast 20 mg BID | 8 |
| Placebo/Apremilast 40 mg QD | 1 |
| Placebo/Apremilast 20 mg BID | 2 |
The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: - percent improvement from Baseline in the 76 swollen joint count, - percent improvement from Baseline in the 78 tender joint count - median percent improvement from Baseline in the following 5 measures ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. The maximal ACR-N for each participant during the 12-week treatment period was calculated, and represents the maximal ACR response achieved. (NCT00456092)
Timeframe: ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12
| Intervention | percent improvement (Mean) |
|---|---|
| Apremilast 40 mg QD | 22.3 |
| Apremilast 20 mg BID | 24.2 |
| Placebo | 10.7 |
The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item asks over the past week whether a particular task can be performed. For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled). (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 40 mg QD | -0.2 |
| Apremilast 20 mg BID | -0.2 |
| Placebo | -0.1 |
The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item asks over the past week whether a particular task can be performed. For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3). The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled). (NCT00456092)
Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Change from Baseline | Change from Week 12 | |
| Apremilast 20 mg BID | -0.2 | -0.0 |
| Apremilast 40 mg QD | -0.1 | 0.0 |
| Placebo/Apremilast 20 mg BID | -0.2 | -0.2 |
| Placebo/Apremilast 40 mg QD | -0.1 | -0.0 |
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit. The time to relapse during the Observational Phase was calculated from the time of maximum ACR reduction and from the date of the Final Treatment Phase visit. Participants classified as responders who did not relapse were censored at the day of the last follow-up. (NCT00456092)
Timeframe: From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2).
| Intervention | days (Median) | |
|---|---|---|
| 1. From Week 12 | 2. From Date of Maximal ACR Response | |
| Apremilast 20 mg BID | 15.0 | 29.0 |
| Apremilast 40 mg QD | 16.0 | 43.0 |
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase (Week 24)/Early Termination Visit. The time to relapse during the Follow-up Phase was calculated from the time of maximum ACR reduction and from the date of the Final Extension Phase visit. Participants classified as responders who did not relapse were censored at the day of the last follow-up. (NCT00456092)
Timeframe: From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2).
| Intervention | days (Median) | |
|---|---|---|
| 1. From Week 12 | 2. From Date of Maximal ACR Response | |
| Apremilast 20 mg BID | 32.0 | 111 |
| Apremilast 40 mg QD | 31.0 | 85.0 |
| Placebo/Apremilast 20 mg BID | 29.0 | 29.0 |
| Placebo/Apremilast 40 mg QD | 16.0 | 16.0 |
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint. The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous. Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment. (NCT00456092)
Timeframe: Week 12 and Week 24
| Intervention | percentage of participants (Number) | |||
|---|---|---|---|---|
| Achilles tendon into the calcaneous: Week 12 | Achilles tendon into the calcaneous: Week 24 | Plantar fascia into the calcaneous:Week 12 | Plantar fascia into the calcaneous: Week 24 | |
| Apremilast 20 mg BID | 15.0 | 15.0 | 17.5 | 7.5 |
| Apremilast 40 mg QD | 17.4 | 19.6 | 15.2 | 13.0 |
| Placebo/Apremilast 20 mg BID | 20.0 | 15.0 | 10.0 | 10.0 |
| Placebo/Apremilast 40 mg QD | 20.0 | 0.0 | 25.0 | 0.0 |
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint. The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous. Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) | |||
|---|---|---|---|---|
| Achilles tendon into the calcaneous: Baseline | Achilles tendon into the calcaneous: Week 12 | Plantar fascia into the calcaneous: Baseline | Plantar fascia into the calcaneous: Week 12 | |
| Apremilast 20 mg BID | 21.7 | 17.4 | 26.1 | 21.7 |
| Apremilast 40 mg QD | 22.4 | 20.9 | 26.9 | 19.4 |
| Placebo | 35.3 | 17.6 | 14.7 | 17.6 |
A modified ACR 50 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85). Participants with no post-baseline ACR scores were considered non-responders. (NCT00456092)
Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Response From Baseline | Response From Week 12 | |
| Apremilast 20 mg BID | 22.5 | 5.9 |
| Apremilast 40 mg QD | 23.9 | 9.7 |
| Placebo/Apremilast 20 mg BID | 15.0 | 5.6 |
| Placebo/Apremilast 40 mg QD | 20.0 | 15.4 |
A modified ACR 20 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein. Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85). Participants with no post-baseline ACR scores were considered non-responders. (NCT00456092)
Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Response From Baseline | Response From Week 12 | |
| Apremilast 20 mg BID | 42.5 | 14.7 |
| Apremilast 40 mg QD | 43.5 | 16.7 |
| Placebo/Apremilast 20 mg BID | 40.0 | 16.7 |
| Placebo/Apremilast 40 mg QD | 45.0 | 15.4 |
The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE). Severe AEs are defined as NCI CTCAE grade 3 or higher. AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event. (NCT00456092)
Timeframe: 12 weeks
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| All adverse events | Adverse events related to study drug | Severe adverse events | Severe adverse events related to study drug | Serious adverse events | Serious adverse events related to study drug | Discontinued study drug due to adverse event | Discontinued due to AE related to study drug | |
| Apremilast 20 mg BID | 59 | 26 | 4 | 1 | 4 | 0 | 10 | 4 |
| Apremilast 40 mg QD | 58 | 27 | 5 | 1 | 0 | 0 | 6 | 5 |
| Placebo | 55 | 26 | 6 | 1 | 4 | 1 | 7 | 1 |
The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE). Severe AEs are defined as NCI CTCAE grade 3 or higher. AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event. A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event. (NCT00456092)
Timeframe: Weeks 12 to 24 (Extension Phase)
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| All adverse events | Adverse events related to study drug | Severe adverse events | Serious adverse events | Serious adverse events related to study drug | Discontinued study drug due to adverse event | Discontinued due to AE related to study drug | |
| Apremilast 20 mg BID | 29 | 8 | 3 | 3 | 0 | 2 | 1 |
| Apremilast 40 mg QD | 30 | 12 | 5 | 2 | 0 | 3 | 1 |
| Placebo/Apremilast 20 mg BID | 11 | 4 | 4 | 1 | 1 | 3 | 1 |
| Placebo/Apremilast 40 mg QD | 16 | 4 | 3 | 1 | 0 | 0 | 0 |
"The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The total score ranges from 0 to 52 with higher scores representing less fatigue." (NCT00456092)
Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Change from Baseline | Change from Week 12 | |
| Apremilast 20 mg BID | 5.9 | 0.1 |
| Apremilast 40 mg QD | 4.4 | -0.3 |
| Placebo/Apremilast 20 mg BID | 1.3 | -1.3 |
| Placebo/Apremilast 40 mg QD | 1.3 | -2.4 |
The Medical Outcome SF 36-Item Health Survey, Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health. The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale. A higher change from baseline indicates an improvement in better health results or functioning. (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Mental Component | Physical Component | |
| Apremilast 20 mg BID | 3.4 | 2.4 |
| Apremilast 40 mg QD | 1.0 | 2.1 |
| Placebo | -0.8 | 0.8 |
The Medical Outcome SF 36-Item Health Survey, Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health. The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale. A higher change from baseline indicates an improvement in better health results or functioning. (NCT00456092)
Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24
| Intervention | units on a scale (Mean) | |||
|---|---|---|---|---|
| Mental Component: Change from Baseline | Mental Component: Change from Week 12 | Physical Component: Change from Baseline | Physical Component: Change from Week 12 | |
| Apremilast 20 mg BID | 1.4 | -2.4 | 4.4 | 1.0 |
| Apremilast 40 mg QD | 0.2 | -1.1 | 3.2 | 0.3 |
| Placebo/Apremilast 20 mg BID | -1.0 | -3.4 | 4.2 | 2.5 |
| Placebo/Apremilast 40 mg QD | -2.7 | -2.5 | 1.8 | -0.1 |
The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Each question is answered on a scale from 0 (not at all) to 3 (very much) The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life. (NCT00456092)
Timeframe: Baseline (Day 1), Week 12 (Day 85) and Week 24
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Change from Baseline | Change from Week 12 | |
| Apremilast 20 mg BID | -1.5 | -0.1 |
| Apremilast 40 mg QD | -3.0 | -0.0 |
| Placebo/Apremilast 20 mg BID | -1.9 | -2.0 |
| Placebo/Apremilast 40 mg QD | -2.6 | -1.2 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis). The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60. Change in the dactylitis severity score was assessed from Baseline (Day 1) and from Week 12 (Day 85). (NCT00456092)
Timeframe: Baseline, Week 12 and Week 24
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Change from Baseline | Change from Week 12 | |
| Apremilast 20 mg BID | -1.5 | -0.2 |
| Apremilast 40 mg QD | -0.4 | 0.3 |
| Placebo/Apremilast 20 mg BID | 0.1 | -0.8 |
| Placebo/Apremilast 40 mg QD | -1.8 | -0.3 |
The Kaplan-Meier estimates of time to ACR 70 response was calculated for participants who had an ACR 70 response at any time during the treatment phase. (NCT00456092)
Timeframe: Baseline to Week 12
| Intervention | days (Median) |
|---|---|
| Apremilast 40 mg QD | 62.0 |
| Apremilast 20 mg BID | 57.0 |
| Placebo | 58.0 |
Time to ACR 70 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 70 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 70 response were calculated for participants who had an ACR 70 response at any time during the study. (NCT00456092)
Timeframe: Baseline to Week 24
| Intervention | days (Median) |
|---|---|
| Apremilast 40 mg QD | 138.0 |
| Apremilast 20 mg BID | 85.0 |
The Kaplan-Meier estimates of time to ACR 50 response was calculated for participants who had an ACR 50 response at any time during the treatment phase. (NCT00456092)
Timeframe: Baseline to Week 12
| Intervention | days (Median) |
|---|---|
| Apremilast 40 mg QD | 43.0 |
| Apremilast 20 mg BID | 57.5 |
| Placebo | 15.0 |
Time to ACR 50 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 50 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 50 response were calculated for participants who had an ACR 50 response at any time during the study. (NCT00456092)
Timeframe: Baseline to Week 24
| Intervention | days (Median) |
|---|---|
| Apremilast 40 mg QD | 71.0 |
| Apremilast 20 mg BID | 58.5 |
| Placebo/Apremilast 40 mg QD | 84.5 |
| Placebo/Apremilast 20 mg BID | 55.0 |
The Kaplan-Meier estimates of time to ACR 20 response was calculated for participants who had an ACR 20 response at any time during the treatment phase. (NCT00456092)
Timeframe: Baseline to Week 12
| Intervention | days (Median) |
|---|---|
| Apremilast 40 mg QD | 29.0 |
| Apremilast 20 mg BID | 30.0 |
| Placebo | 29.0 |
Time to ACR 20 was measured from the first dose of apremilast to the first time a participant achieved an ACR 20 response in the treatment or extension phase. The Kaplan-Meier estimates of time to ACR 20 response were calculated for participants who had an ACR 20 response at any time during the study. (NCT00456092)
Timeframe: Baseline to Week 24
| Intervention | days (Median) |
|---|---|
| Apremilast 40 mg QD | 43.0 |
| Apremilast 20 mg BID | 43.0 |
| Placebo/Apremilast 40 mg QD | 34.0 |
| Placebo/Apremilast 20 mg BID | 55.5 |
The DAS28 measures the severity of disease at a specific time. DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (TJC; does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count (SJC) • C-reactive protein (CRP) • Patient's global assessment of disease activity (GH) according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity. A EULAR response reflects an improvement in disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and a DAS28 score ≤ 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2 (NCT00456092)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 40 mg QD | 49.3 |
| Apremilast 20 mg BID | 55.1 |
| Placebo | 38.2 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -68.3 |
The BSA estimate was based on the palm area of the hand of the participant which equates to 1% of the total body surface area. (NCT00521339)
Timeframe: Baseline to Week 12
| Intervention | Percent change in BSA (Mean) |
|---|---|
| Apremilast 20 mg | -53.0 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Week 0 to Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -42.7 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -54.6 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -88.6 |
"TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.~Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event." (NCT00521339)
Timeframe: Week 12 to Week 24
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| ≥ 1 AE | ≥ 1 AE with a suspected relationship to study drug | ≥ 1 severe AE | ≥ 1 SAE | |
| Apremilast 20mg/20mg (Extension Phase) | 4 | 0 | 1 | 0 |
| Apremilast 20mg/30mg (Extension Phase) | 5 | 2 | 1 | 1 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -47.4 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -12.5 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -100.0 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -66.5 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -25.0 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -49.4 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -26.5 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | 14.2 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) i being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -82.3 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -36.4 |
The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 20 mg | -59.0 |
The maximum observed plasma concentration of apremilast (Cmax); the maximum plasma concentration (Cmax) was obtained directly from the observed concentration-time data on Days 1, 85, and 169/170, respectively. (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast 20mg | 364.85 |
The maximum observed plasma concentration of CC-10004 (Cmax); the maximum plasma concentration (Cmax) was obtained directly from the observed concentration-time data on Days 169/170. (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast 20mg/30mg PO BID (Treatment + Extension Phase) | 320.35 |
Mean Residence Time (MRT) is defined as the mean duration of time the drug spends in the body. The average concentration at steady state (Cavg) (for Day 85 was calculated as follows: Cavg = (Day 85 AUC0-12)/(12). (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | hours (Geometric Mean) |
|---|---|
| Apremilast 20mg PO BID | 202.04 |
Mean Residence Time (MRT) is defined as the mean duration of time the drug spends in the body. The average concentration at steady state (Cavg) (for Days169/170) was calculated as follows: Cavg = (Day 169/170)/(12) (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | hours (Geometric Mean) |
|---|---|
| Apremilast 20mg/30mg PO BID (Treatment + Extension Phase) | 168.3092 |
DLQI was the dermatology-specific quality of life (QOL) measure used for the psoriatic population. The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on a participants QoL, based on recall over the past week. Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment. Possible responses for each of the 10 items are: not at all, a little, a lot, and very much. Each question is rated on a scale of 0 to 3 with a total range of 0 to 30. Higher scores indicate greater impact of disease on QOL (NCT00521339)
Timeframe: Baseline to Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -4.7 |
Plasma concentrations of apremilast were determined using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Apremilast 20/30mg BID | 2019.71 |
"Plasma concentrations of apremilast were determined using validated chiral liquid chromatography-mass spectrometry methods (LC-MS/MS). For Day 1, AUC0-12 was calculated, using linear trapezoidal area method in WinNonlin (linear-linear trapezoidal). For Days 85 and 169/170, the AUC during a dosing interval (12 hours) (AUC0-12), was calculated at steady-state using the partial area function within WinNonlin.~." (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Apremilast 20mg | 2424.48 |
"Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) (for Days 1, 85, and 169/170)~For Day 1, Vz/F was not calculated.~For Days 85 and 169/170, apparent volume of distribution of drug (V/z) based on the terminal phase was calculated as follows: Vz/F=Dose/(λ*AUC^12)" (NCT00521339)
Timeframe: Day 85
| Intervention | mL (Geometric Mean) |
|---|---|
| Apremilast 20mg | 107616.08 |
For Days 169/170, apparent volume of distribution of drug (V/z) based on the terminal phase was calculated as follows: Vz/F=Dose/(λ*AUC12) where λ = the terminal elimination rate constant (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | mL (Geometric Mean) |
|---|---|
| Apremilast 20mg BID/30mg PO BID (Treatment + Extension Phase) | 134734.60 |
"The apparent total clearance of apremilast from plasma after extravascular administration (CLz/F); for Day 1, apparent clearance of drug from plasma (CL/F) was not calculated.~For Day 85, Apparent clearance of drug from plasma after extravascular administration (CL/F) was calculated as follows: CL/F= Dose/AUC^12 where τ=12." (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | mL/hour (Geometric Mean) |
|---|---|
| Apremilast 20mg | 8249.19 |
For 169/170, apparent clearance of drug from plasma after extravascular administration (CL/F) was calculated as follows: CL/F= Dose/AUC12 (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | mL/hour (Geometric Mean) |
|---|---|
| Apremilast 20mg/30mg PO BID (Treatment + Extension Phase) | 14853.59 |
"TEAE = any AE occurring or worsening on or after the first treatment with any study drug. Related = suspected by investigator to be related to study treatment. National Cancer Institute [NCI] Common Toxicity Criteria for Adverse Events [CTCAE], Version 3.0, grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, 5 = death.~Adverse event (AE) = any noxious, unintended, or untoward medical occurrence occurring at any dose that may appear or worsen in a participant during the course of a study, including new intercurrent illness, worsening concomitant illness, injury, or any concomitant impairment of participant's health, including laboratory test values, regardless of etiology. Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event." (NCT00521339)
Timeframe: Week 0 to Week 12
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| ≥ 1 AE | ≥ 1 AE with a suspected relationship to study drug | ≥ 1 severe AE | ≥ 1Severe AE suspected to be related to study drug | ≥ 1 SAE | ≥ AE leading to study drug discontinuation | >=1 treatment-related AE drug discontinued | |
| Apremilast 20 mg | 25 | 13 | 3 | 1 | 0 | 4 | 2 |
The SF-36 was a self-administered instrument consisting of 8 multi-item scales that assess 8 health domains: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. A higher score post-baseline is indicative of improvement in the disease state. The summary physical health score included physical functioning, role-physical, bodily pain and general health. The summary mental health score included: vitality, social functioning, role-emotional and mental health. The resulting score for each subscale is then standardized, to obtain values ranging from 0 to 100, with higher values indicating a better QOL. (NCT00521339)
Timeframe: Baseline to Week 12
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Mental Component | Physical Component | |
| Apremilast 20 mg | 0.8 | 2.4 |
T cells or T lymphocytes, a type of white blood cell, play a role in cell-mediated immunity. T cells are distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on the cell surface and mature in the thymus. B cells, a type of lymphocyte in the humoral immunity of the adaptive immune system can be distinguished by the presence of a protein on the B cells outer surface called a B cell receptor (BCR). This receptor protein allows a B cell to bind to a specific antigen and make antibodies against antigens [(antigen-presenting cells APCs)], and to develop into memory B cells after activation by antigen interaction. Natural Killer Cells (NK) are a type of cytotoxic lymphocyte critical to the innate immune system. Their role is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. They constitute the third kind of cells differentiated from the common lymphoid progenitor generating B and T lymphocytes and mature in the bone marrow. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percentage of lymphocytes (Mean) | ||
|---|---|---|---|
| CD 16 + CD 56 (NK cells) | CD 19 (B-cells) | CD 3 (T-cells) | |
| Apremilast 20 mg PO BID (Treatment Phase) | -0.7 | -0.5 | 0.6 |
The trough observed plasma concentration of apremilast (Cmin) was determined directly from the observed pre-AM dose concentration on Day 85. (NCT00521339)
Timeframe: Day 85 Pre-dose
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast 20mg | 101.36 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -73.3 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -34.3 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -57.9 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | 17.1 |
"A participant was a responder if the following 3 criteria for improvement from baseline were met:~≥ 20% improvement in 78 tender joint count;~≥ 20% improvement in 76 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein." (NCT00521339)
Timeframe: Baseline to Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | 25.0 |
PASI -50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 12. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head,trunk, upper limbs, and lower limbs. Degree of involvement on each of the4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. (NCT00521339)
Timeframe: Baseline to Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 20 mg | 46.7 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 12. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. (NCT00521339)
Timeframe: Baseline to Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 20 mg | 30.00 |
The aim of the study was to measure the pharmacodynamic effects of apremilast in participants with plaque psoriasis in skin affected by psoriasis, immune cells enter the skin through blood vessels and cause the epidermis to grow very rapidly and to stop shedding properly. This causes thickening of the skin as well as the scaly build up composed of dead skin cells seen on areas affected by psoriasis. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -62.0 |
The static Physician's Global Assessment (sPGA) rated the investigator's overall clinical assessment of a participants plaque thickness, erythema, and scaling on a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (majority of plaques have severe thickness, erythema, and scale). To assign a sPGA score, the investigator examined all psoriatic lesions and assigned a severity score ranging from 0 to 5 for thickness, erythema, and scaling. Scores for thickness, erythema, and scaling are summed and the mean of these 3 scores equals the overall sPGA score. Decreases in sPGA correspond to clinical improvement. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | 66.7 |
Terminal phase elimination half-life (t1/2) was calculated as follows: t1/2 = 0.693/λz. The terminal elimination rate constant (λZ) was estimated by linear regression of the log-transformed concentration-time data. (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | Liters (Geometric Mean) |
|---|---|
| Apremilast 20mg | 7.832 |
Terminal phase elimination half-life (t1/2) was calculated as follows: t1/2 = 0.693/λz. The terminal elimination rate constant (λZ) was estimated by linear regression of the log-transformed concentration-time data. (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | hours (Geometric Mean) |
|---|---|
| Apremilast 20mg/30mg PO BID (Treatment + Extension Phase) | 6.287 |
The time to reach Cmax (Tmax) was obtained directly from the observed concentration-time data on Day 169/170. Actual times utilized were used for reporting Tmax values. (NCT00521339)
Timeframe: Day 169 pre-dose, 0.5, 1, 2, 4, 8 12, 24 and 36 hours after AM dose
| Intervention | hours (Geometric Mean) |
|---|---|
| Apremilast 20mg BID/30mg PO BID (Treatment + Extension Phase) | 1.59 |
The time to reach Cmax (Tmax) was obtained directly from the observed concentration-time data on Day 85. Actual times utilized were used for reporting Tmax values. (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | hours (Median) |
|---|---|
| Apremilast 20mg | 2.00 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -37.6 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -100.0 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -78.6 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -52.6 |
Inflammatory markers associated with psoriasis (using skin biopsies) were used to detect acute inflammation and as markers of treatment response. The inflammatory markers were measured using Reverse transcriptase polymerase chain reaction (RT-PCR) and the messenger Ribonucleic acid (mRNA) is being measured. (NCT00521339)
Timeframe: Baseline and Week 12
| Intervention | percent change (Median) |
|---|---|
| Apremilast 20 mg PO BID (Treatment Phase) | -86.7 |
Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug. (NCT00521339)
Timeframe: Day 85 Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours after the AM dose
| Intervention | ratio (Geometric Mean) |
|---|---|
| Apremilast 20mg | 1.68 |
"The primary efficacy measure was a Global Response Assessment (GRA), a subject completed questionnaire that measures improvement in overall symptoms on a 7-point scale: Markedly Improved - 7, Moderately Improved - 6, Mildly Improved - 5, Same - 4, Mildly Worse - 3, Moderately Worse - 2, Markedly Worse - 1.~The primary outcome showing response to treatment was the number of subjects that were moderately or markedly improved on the GRA scale." (NCT00701311)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|---|
| CC-10004 | 2 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -5.8 |
| Apremilast 20mg BID | -6.1 |
| Apremilast 30 mg BID | -5.6 |
| Placebo-Apremilast 20mg BID | -6.8 |
| Placebo-Apremilast 30 mg BID | -4.9 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 40 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 8.5 |
| Apremilast 20mg BID | 14.0 |
| Apremilast 30 mg BID | 17.2 |
| Placebo-Apremilast 20mg BID | 18.5 |
| Placebo-Apremilast 30 mg BID | 22.2 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 32 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 10.6 |
| Apremilast 20mg BID | 14.0 |
| Apremilast 30 mg BID | 19.0 |
| Placebo-Apremilast 20mg BID | 18.5 |
| Placebo-Apremilast 30 mg BID | 25.9 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 52. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 14.9 |
| Apremilast 20mg BID | 22.0 |
| Apremilast 30 mg BID | 36.2 |
| Placebo-Apremilast 20mg BID | 37.0 |
| Placebo-Apremilast 30 mg BID | 33.3 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 40 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 21.3 |
| Apremilast 20mg BID | 28.0 |
| Apremilast 30 mg BID | 34.5 |
| Placebo-Apremilast 20mg BID | 37.0 |
| Placebo-Apremilast 30 mg BID | 44.4 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 32 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 27.7 |
| Apremilast 20mg BID | 38.0 |
| Apremilast 30 mg BID | 46.6 |
| Placebo-Apremilast 20mg BID | 33.3 |
| Placebo-Apremilast 30 mg BID | 55.6 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 52 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 42.6 |
| Apremilast 20mg BID | 48.0 |
| Apremilast 30 mg BID | 72.4 |
| Placebo-Apremilast 20mg BID | 55.6 |
| Placebo-Apremilast 30 mg BID | 48.1 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 48.9 |
| Apremilast 20mg BID | 62.0 |
| Apremilast 30 mg BID | 82.8 |
| Placebo-Apremilast 20mg BID | 63.0 |
| Placebo-Apremilast 30 mg BID | 66.7 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 32 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 57.4 |
| Apremilast 20mg BID | 72.0 |
| Apremilast 30 mg BID | 86.2 |
| Placebo-Apremilast 20mg BID | 74.1 |
| Placebo-Apremilast 30 mg BID | 74.1 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -55.1 |
| Apremilast 20mg BID | -58.9 |
| Apremilast 30 mg BID | -65.3 |
| Placebo-Apremilast 20mg BID | -62.7 |
| Placebo-Apremilast 30 mg BID | -62.0 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -55.9 |
| Apremilast 20mg BID | -63.3 |
| Apremilast 30 mg BID | -71.1 |
| Placebo-Apremilast 20mg BID | -64.5 |
| Placebo-Apremilast 30 mg BID | -71.7 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -51.0 |
| Apremilast 20mg BID | -63.1 |
| Apremilast 30 mg BID | -72.7 |
| Placebo-Apremilast 20mg BID | -64.0 |
| Placebo-Apremilast 30 mg BID | -69.2 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -53.1 |
| Apremilast 20mg BID | -58.3 |
| Apremilast 30 mg BID | -67.3 |
| Placebo-Apremilast 20mg BID | -67.4 |
| Placebo-Apremilast 30 mg BID | -64.9 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -55.4 |
| Apremilast 20mg BID | -65.4 |
| Apremilast 30 mg BID | -74.3 |
| Placebo-Apremilast 20mg BID | -66.2 |
| Placebo-Apremilast 30 mg BID | -68.0 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -47.1 |
| Apremilast 20mg BID | -65.1 |
| Apremilast 30 mg BID | -75.3 |
| Placebo-Apremilast 20mg BID | -62.6 |
| Placebo-Apremilast 30 mg BID | -66.7 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value.. (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 1.2 |
| Apremilast 20mg BID | 1.2 |
| Apremilast 30 mg BID | 2.0 |
| Placebo-Apremilast 20mg BID | 3.4 |
| Placebo-Apremilast 30 mg BID | 0.3 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 1.4 |
| Apremilast 20mg BID | 2.6 |
| Apremilast 30 mg BID | 1.8 |
| Placebo-Apremilast 20mg BID | 3.1 |
| Placebo-Apremilast 30 mg BID | 1.5 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 5.1 |
| Apremilast 20mg BID | 4.1 |
| Apremilast 30 mg BID | 2.4 |
| Placebo-Apremilast 20mg BID | 4.7 |
| Placebo-Apremilast 30 mg BID | 3.4 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 5.4 |
| Apremilast 20mg BID | 4.8 |
| Apremilast 30 mg BID | 1.7 |
| Placebo-Apremilast 20mg BID | 2.9 |
| Placebo-Apremilast 30 mg BID | 3.8 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 5.2 |
| Apremilast 20mg BID | 3.8 |
| Apremilast 30 mg BID | 2.9 |
| Placebo-Apremilast 20mg BID | 4.6 |
| Placebo-Apremilast 30 mg BID | 2.8 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -0.2 |
| Apremilast 20mg BID | 1.6 |
| Apremilast 30 mg BID | 1.7 |
| Placebo-Apremilast 20mg BID | 3.2 |
| Placebo-Apremilast 30 mg BID | 1.8 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -5.5 |
| Apremilast 20mg BID | -6.6 |
| Apremilast 30 mg BID | -6.4 |
| Placebo-Apremilast 20mg BID | -7.1 |
| Placebo-Apremilast 30 mg BID | -5.9 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -6.5 |
| Apremilast 20mg BID | -7.5 |
| Apremilast 30 mg BID | -6.0 |
| Placebo-Apremilast 20mg BID | -8.1 |
| Placebo-Apremilast 30 mg BID | 5.5 |
Time to achieve maximum plasma concentration (tmax) observed at Week 24 (Time to achieve steady-state Tmax) (NCT00773734)
Timeframe: Week 24
| Intervention | hours (Median) |
|---|---|
| Apremilast 10mg BID | 1.00 |
| Apremilast 20mg BID | 1.50 |
| Apremilast 30 mg BID | 1.00 |
Time to achieve maximum plasma concentration (Cmax) observed at Week 14 (Time to achieve steady-state Tmax) (NCT00773734)
Timeframe: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast
| Intervention | hours (Median) |
|---|---|
| Apremilast 10mg BID | 2.00 |
| Apremilast 20mg BID | 2.00 |
| Apremilast 30 mg BID | 1.00 |
For PASI-75 responders in the placebo-controlled period Weeks 0-16, time to achieve PASI-75 was defined as the time interval, inclusive between the date of randomization (day 1) and the date of the first assessment where PASI-75 is achieved. (NCT00773734)
Timeframe: Weeks 0 to 16
| Intervention | weeks (Median) |
|---|---|
| Placebo BID | 8.1 |
| Apremilast 10mg BID | 10.0 |
| Apremilast 20mg BID | 11.9 |
| Apremilast 30 mg BID | 6.3 |
For PASI-50 responders in the placebo-controlled period weeks 0-16, time to achieve PASI-50 was defined as the time interval, inclusive between the date of randomization (day 1) and the date of the first assessment where PASI-50 was achieved. (NCT00773734)
Timeframe: Week 0 to 16
| Intervention | weeks (Median) |
|---|---|
| Placebo BID | 6.5 |
| Apremilast 10mg BID | 5.9 |
| Apremilast 20mg BID | 6.0 |
| Apremilast 30 mg BID | 4.3 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 12.6 |
| Apremilast 10mg | 10.5 |
| Apremilast 20mg | 25.0 |
| Apremilast 30 mg | 33.7 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease (NCT00773734)
Timeframe: Week 0 and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 13.5 |
| Apremilast 20mg BID | 24.1 |
| Apremilast 30 mg BID | 34.1 |
| Placebo-Apremilast 20 mg BID | 41.2 |
| Placebo-Apremilast 30 mg BID | 50.0 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy..The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg | 4.5 |
| Apremilast 20mg | 8.0 |
| Apremilast 30 mg | 14.8 |
| PBO-Apremilast 20mg BID | 14.7 |
| Placebo-Apremilast 30 mg BID | 16.7 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo BID | 1.1 |
| Apremilast 10mg BID | 4.5 |
| Apremilast 20mg BID | 9.2 |
| Apremilast 30 mg BID | 11.4 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo BID | 5.7 |
| Apremilast 10mg BID | 11.2 |
| Apremilast 20mg BID | 28.7 |
| Apremilast 30 mg BID | 40.9 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy.The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head,trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 18.0 |
| Apremilast 20mg BID | 26.4 |
| Apremilast 30 mg BID | 39.8 |
| PBO-Apremilast 20mg BID | 41.2 |
| PBO-Apremilast 30 mg BID | 44.4 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 24. The improvement in PASI score was used as a measure of efficacy. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 38.2 |
| Apremilast 20mg | 49.4 |
| Apremilast 30 mg BID | 65.9 |
| Placebo-Apremilast 20mg BID | 61.8 |
| PBO-Apremilast 30 mg BID | 75.0 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo BID | 25.0 |
| Apremilast 10mg BID | 38.2 |
| Apremilast 20mg BID | 47.1 |
| Apremilast 30 mg BID | 60.2 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo BID | -8.0 |
| Apremilast 10mg BID | -28.3 |
| Apremilast 20mg BID | -38.0 |
| Apremilast 30 mg BID | -50.4 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -28.1 |
| Apremilast 20mg BID | -40.6 |
| Apremilast 30 mg BID | -54.0 |
| Placebo-Apremilast 20 mg BID | -52.5 |
| Placebo-Apremilast 30 mg BID | -54.2 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -36.3 |
| Apremilast 20mg BID | -46.5 |
| Apremilast 30 mg BID | -56.8 |
| PBO-Apremilast 20mg BID | -61.7 |
| PBO-Apremilast 30 mg BID | -61.7 |
The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score. (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | Percent change (Least Squares Mean) |
|---|---|
| Placebo BID | -20.3 |
| Apremilast 10mg BID | -34.0 |
| Apremilast 20mg BID | -45.4 |
| Apremilast 30 mg BID | -53.2 |
The maximum observed plasma concentration of apremilast observed at Week 24 (steady-state Cmax) (NCT00773734)
Timeframe: Week 24
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast 10mg BID | 238 |
| Apremilast 20mg BID | 236 |
| Apremilast 30 mg BID | 670 |
The maximum observed plasma concentration of apremilast observed at Week 14 (steady-state Cmax) (NCT00773734)
Timeframe: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast 10mg BID | 209 |
| Apremilast 20mg BID | 298 |
| Apremilast 30 mg BID | 637 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo BID | 0.7 |
| Apremilast 10mg BID | 1.3 |
| Apremilast 20mg BID | 2.1 |
| Apremilast 30 mg BID | 0.8 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 2.8 |
| Apremilast 20mg BID | 3.9 |
| Apremilast 30 mg BID | 2.9 |
| PBO-Apremilast 20mg BID | 2.8 |
| PBO-Apremilast 30 mg BID | 0.5 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo BID | -0.6 |
| Apremilast 10mg BID | 2.8 |
| Apremilast 20mg BID | 2.9 |
| Apremilast 30 mg BID | 3.0 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 1.1 |
| Apremilast 20mg BID | 2.3 |
| Apremilast 30 mg BID | 1.0 |
| PBO-Apremilast 20mg BID | 2.5 |
| PBO-Apremilast 30 mg BID | 2.7 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Week 24
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -3.4 |
| Apremilast 20mg BID | -6.2 |
| Apremilast 30 mg BID | -4.9 |
| Placebo-Apremilast (APR) 20 mg BID | -6.4 |
| Placebo-Apremilast 30 mg BID | -5.4 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo BID | -1.9 |
| Apremilast 10mg BID | -3.2 |
| Apremilast 20mg BID | -5.9 |
| Apremilast 30 mg BID | -4.4 |
Area under the concentration versus time curve from time 0 (pre-dose) to 8 hours, calculated using the linear trapezoid rule. (NCT00773734)
Timeframe: Week 14; Predose, 0.5, 1, 2, 3, 4, and 8 hours after the morning dose of apremilast
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Apremilast 10mg BID | 1008 |
| Apremilast 20mg BID | 1591 |
| Apremilast 30 mg BID | 3467 |
Area under the concentration versus time curve from time 0 (pre-dose) to 8 hours, calculate using the linear trapezoid rule. (NCT00773734)
Timeframe: Week 24
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Apremilast 10mg | 1200 |
| Apremilast 20mg | 1257 |
| Apremilast 30 mg | 3477 |
Time to loss of response was modified to be 50% loss in the PASI response observed at the end of treatment for participants who achieved at least a PASI-50 at the end of treatment. This definition was changed since participants may have already lost their maximal PASI response prior to enrollment into the Observation Follow-up Phase. Included all participants that enrolled into the observational follow-up phase after the treatment phase. (NCT00773734)
Timeframe: Up to 4 weeks after the last dose
| Intervention | weeks (Median) |
|---|---|
| Apremilast 10mg BID | NA |
| Apremilast 20mg BID | NA |
| Apremilast 30 mg BID | NA |
| Placebo-Apremilast 20mg BID | NA |
| Placebo-Apremilast 30 mg BID | 5.3 |
An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT00773734)
Timeframe: Week 0 to Week 16; up to data cut off of 21 July 2011
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any treatment emergent AE | Any drug-related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug-related | ≥ 1 TEAE leading to drug interruption | ≥ 1 TEAE leading to drug withdrawal | ≥ 1 TEAE leading to death | |
| Apremilast 10mg BID | 59 | 20 | 1 | 0 | 0 | 3 | 2 | 0 |
| Apremilast 20mg BID | 67 | 23 | 5 | 3 | 0 | 3 | 8 | 0 |
| Apremilast 30 mg BID | 72 | 32 | 5 | 4 | 0 | 6 | 12 | 0 |
| Placebo | 57 | 11 | 3 | 2 | 0 | 4 | 5 | 1 |
An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT00773734)
Timeframe: Week 0-88; up to data cut off of 21 July 2011
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any treatment emergent AE | Any drug-related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug-related | ≥ 1 TEAE leading to drug interruption | ≥ 1 TEAE leading to drug withdrawal | ≥ 1 TEAE leading to death | |
| Apremilast 10mg BID | 67 | 23 | 3 | 1 | 0 | 3 | 5 | 0 |
| Apremilast 20mg BID | 97 | 31 | 9 | 8 | 1 | 11 | 11 | 0 |
| Apremilast 30 mg BID | 110 | 45 | 13 | 6 | 0 | 9 | 15 | 0 |
An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT00773734)
Timeframe: Week 0 to 6 years of study treatment; maximum duration of exposure was 314.6 weeks
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any treatment emergent AE | Any drug-related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug-related | ≥ 1 TEAE leading to drug interruption | ≥ 1 TEAE leading to drug withdrawal | ≥ 1 TEAE leading to death | |
| Apremilast 10mg BID | 67 | 23 | 4 | 2 | 0 | 3 | 5 | 0 |
| Apremilast 20mg BID | 97 | 32 | 10 | 9 | 1 | 11 | 11 | 0 |
| Apremilast 30 mg BID | 111 | 46 | 14 | 6 | 0 | 10 | 16 | 0 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 20.0 |
| Placebo-Apremilast 20 mg BID | 0.0 |
| Apremilast 20mg BID | 0.0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 30.0 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease (NCT00773734)
Timeframe: Week 0 and month 36
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 60.0 |
| Placebo-Apremilast 20 mg BID | 0.0 |
| Apremilast 20mg BID | 0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 30.0 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 20.0 |
| Placebo-Apremilast 20 mg BID | 0.00 |
| Apremilast 20mg BID | 10.0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 40.0 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 60.0 |
| Placebo-Apremilast 20 mg BID | 0.0 |
| Apremilast 20mg BID | 20.0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 60.0 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 196 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 0.0 |
| Placebo-Apremilast 20mg BID | 0.0 |
| Apremilast 20mg BID | 0.0 |
| Placebo-Apremilast 30 mg BID | 0.0 |
| Apremilast 30 mg BID | 20.0 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 148 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 20.0 |
| Placebo-Apremilast 20mg BID | 0.0 |
| Apremilast 20mg BID | 10.0 |
| Placebo-Apremilast 30 mg BID | 0.0 |
| Apremilast 30 mg BID | 20.0 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 100 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 0.0 |
| Placebo-Apremilast 20mg BID | 0 |
| Apremilast 20mg BID | 10.0 |
| Placebo-Apremilast 30 mg BID | 0.0 |
| Apremilast 30 mg BID | 30.0 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 76 of the long-term extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 0.0 |
| Placebo-Apremilast 20mg BID | 0.0 |
| Apremilast 20mg BID | 10.0 |
| Placebo-Apremilast 30 mg BID | 0.0 |
| Apremilast 30 mg BID | 30.0 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 40.0 |
| Placebo-Apremilast 20mg BID | 0.0 |
| Apremilast 20mg BID | 0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 30.0 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 60.0 |
| Placebo-Apremilast 20mg BID | 25.0 |
| Apremilast 20mg BID | 10.0 |
| Placebo-Apremilast 30 mg BID | 0.0 |
| Apremilast 30 mg BID | 30.0 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 20.0 |
| Placebo-Apremilast 20mg BID | 0.0 |
| Apremilast 20mg BID | 30.0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 50.0 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 60.0 |
| Placebo-Apremilast 20mg BID | 0.0 |
| Apremilast 20mg BID | 40.0 |
| Placebo-Apremilast 30 mg BID | 0.0 |
| Apremilast 30 mg BID | 50.0 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 40.0 |
| Placebo-Apremilast 20mg BID | 25.0 |
| Apremilast 20mg BID | 20.0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 40.0 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 60.0 |
| Placebo-Apremilast 20mg BID | 50.0 |
| Apremilast 20mg BID | 30.0 |
| Placebo-Apremilast 30 mg BID | 50.0 |
| Apremilast 30 mg BID | 60.0 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 60.0 |
| Placebo-Apremilast 20mg BID | 50.0 |
| Apremilast 20mg BID | 50.0 |
| Placebo-Apremilast 30 mg BID | 25.0 |
| Apremilast 30 mg BID | 90.0 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 100.0 |
| Placebo-Apremilast 20mg BID | 50.0 |
| Apremilast 20mg BID | 70.0 |
| Placebo-Apremilast 30 mg BID | 50.0 |
| Apremilast 30 mg BID | 100 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -75.0 |
| Placebo-Apremilast 20 mg BID | -50.6 |
| Apremilast 20mg BID | -72.4 |
| Placebo-Apremilast 30 mg BID | -75.0 |
| Apremilast 30 mg BID | -86.1 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -86.1 |
| Placebo-Apremilast 20 mg BID | -63.4 |
| Apremilast 20mg BID | -58.4 |
| Placebo-Apremilast 30 mg BID | -39.1 |
| Apremilast 30 mg BID | -78.5 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -64.7 |
| Placebo-Apremilast 20 mg BID | -66.2 |
| Apremilast 20mg BID | -74.5 |
| Placebo-Apremilast 30 mg BID | -24.7 |
| Apremilast 30 mg BID | -74.5 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -71.1 |
| Placebo-Apremilast 20 mg BID | -73.9 |
| Apremilast 20mg BID | -74.2 |
| Placebo-Apremilast 30 mg BID | -44.2 |
| Apremilast 30 mg BID | -76.7 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -82.5 |
| PBO-Apremilast 20mg BID | -52.0 |
| Apremilast 20mg BID | -54.3 |
| PBO-Apremilast 30 mg BID | -80.0 |
| Apremilast 30 mg BID | -85.0 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -87.7 |
| PBO-Apremilast 20mg BID | -69.0 |
| Apremilast 20mg BID | -48.8 |
| PBO-Apremilast 30 mg BID | -48.0 |
| Apremilast 30 mg BID | -80.0 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -57.8 |
| PBO-Apremilast 20mg BID | -64.5 |
| Apremilast 20mg BID | -65.9 |
| PBO-Apremilast 30 mg BID | -46.0 |
| Apremilast 30 mg BID | -78.4 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling were scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions was scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. The values for each anatomic region were summed to yield the PASI score (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percent change (Mean) |
|---|---|
| Apremilast 10mg BID | -71.8 |
| PBO-Apremilast 20mg BID | -60.5 |
| Apremilast 20mg BID | -65.3 |
| PBO-Apremilast 30 mg BID | -50.0 |
| Apremilast 30 mg BID | -77.3 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | percent change (Median) |
|---|---|
| Apremilast 10mg BID | -75.0 |
| Placebo-Apremilast 20 mg BID | -50.6 |
| Apremilast 20mg BID | -73.5 |
| Placebo-Apremilast 30 mg BID | -75.0 |
| Apremilast 30 mg BID | -91.9 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | percent change (Median) |
|---|---|
| Apremilast 10mg BID | -85.7 |
| Placebo-Apremilast 20 mg BID | -63.4 |
| Apremilast 20mg BID | -60.9 |
| Placebo-Apremilast 30 mg BID | -52.2 |
| Apremilast 30 mg BID | -81.0 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | percent change (Median) |
|---|---|
| Apremilast 10mg BID | -60.5 |
| Placebo-Apremilast 20 mg BID | -66.2 |
| Apremilast 20mg BID | -75.0 |
| Apremilast 30 mg BID | -41.5 |
| Placebo-Apremilast 30 mg BID | -77.4 |
"The overall BSA affected by psoriasis was estimated by comparison of the size of the affected area to the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | percent change (Median) |
|---|---|
| Apremilast 10mg BID | -78.6 |
| Placebo-Apremilast 20 mg BID | -73.9 |
| Apremilast 20mg BID | -73.3 |
| Placebo-Apremilast 30 mg BID | -49.2 |
| Apremilast 30 mg BID | -86.4 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20mg BID | 10.2 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 1.4 |
| Placebo-Apremilast 20mg BID | 2.0 |
| Apremilast 20mg BID | -4.1 |
| Placebo-Apremilast 30 mg BID | 10.2 |
| Apremilast 30 mg BID | 9.4 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 6.6 |
| Placebo-Apremilast 20mg BID | 1.0 |
| Apremilast 20mg BID | -0.1 |
| Placebo-Apremilast 30 mg BID | 4.4 |
| Apremilast 30 mg BID | 4.2 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 4.1 |
| Placebo-Apremilast 20mg BID | 3.7 |
| Apremilast 20mg BID | 1.0 |
| Placebo-Apremilast 30 mg BID | 2.4 |
| Apremilast 30 mg BID | 5.0 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -1.1 |
| Placebo-Apremilast 20mg BID | 4.1 |
| Apremilast 20mg BID | -1.0 |
| Placebo-Apremilast 30 mg BID | 17.6 |
| Apremilast 30 mg BID | 1.2 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 6.0 |
| Placebo-Apremilast 20mg BID | -2.7 |
| Apremilast 20mg BID | 3.6 |
| Placebo-Apremilast 30 mg BID | 2.1 |
| Apremilast 30 mg BID | 2.4 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | 5.0 |
| Placebo-Apremilast 20mg BID | 2.0 |
| Apremilast 20mg BID | 5.2 |
| Placebo-Apremilast 30 mg BID | 4.5 |
| Apremilast 30 mg BID | 0.2 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20mg BID | -2.8 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Month 48
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -6.0 |
| Placebo-Apremilast 20mg BID | -9.0 |
| Apremilast 20mg BID | -3.5 |
| Placebo-Apremilast 30 mg BID | -7.0 |
| Apremilast 30 mg BID | -10.3 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Month 36
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -11.7 |
| Placebo-Apremilast 20mg BID | -3.0 |
| Apremilast 20mg BID | -4.2 |
| Placebo-Apremilast 30 mg BID | -2.0 |
| Apremilast 30 mg BID | -6.0 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Month 24
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 10mg BID | -5.2 |
| Placebo-Apremilast 20mg BID | -13.5 |
| Apremilast 20mg BID | -5.9 |
| Placebo-Apremilast 30 mg BID | -1.8 |
| Apremilast 30 mg BID | -6.8 |
The DLQI was a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on subjects' quality of life, based on recall over the past week. Domains include symptoms, feelings, daily activities, social, leisure, work or studying, personal relationships and treatment. Each question on the extent of the impact of skin disease was answered on a scale of 0 (not at all) to 3 (very much); the total DLQI score ranged from 0 to 30. A DLQI score greater than 10 is indicative of severe psoriasis. (NCT00773734)
Timeframe: Week 0 to Month 18
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20mg BID | -6.5 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease. (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 12.8 |
| Apremilast 20mg BID | 10.0 |
| Apremilast 30 mg BID | 22.4 |
| Placebo-Apremilast 20mg BID | 33.3 |
| Placebo-Apremilast 30 mg BID | 22.2 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less disease. (NCT00773734)
Timeframe: Week 0 to Week 40
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 23.4 |
| Apremilast 20mg BID | 18.0 |
| Apremilast 30 mg BID | 29.3 |
| Placebo-Apremilast 20mg BID | 29.6 |
| Placebo-Apremilast 30 mg BID | 37.0 |
The sPGA was a measure of psoriasis disease severity at the time of evaluation by the investigator. It does not compare assessments across visits or rely on investigator recall of prior disease severity. The sPGA was a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examined all of the lesions on the participant and assigned a score ranging from 0 to 5 for thickness, erythema and degree of scaling . Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equaled the overall sPGA score. Fractional values for the sPGA were rounded to the next highest integer (eg, a score of 3.5 was rounded to 4, 3.4 was rounded to 3). A lower sPGA score was associated with less severe disease. (NCT00773734)
Timeframe: Week 0 to Week 32
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 23.4 |
| Apremilast 20mg BID | 26 |
| Apremilast 30 mg BID | 44.8 |
| Placebo-Apremilast 20mg BID | 33.3 |
| Placebo-Apremilast 30 mg BID | 59.3 |
PASI-90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from baseline in PASI score at Week 52 of the extension study. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). (NCT00773734)
Timeframe: Week 0 to Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast 10mg BID | 4.3 |
| Apremilast 20mg BID | 10.0 |
| Apremilast 30 mg BID | 13.8 |
| Placebo-Apremilast 20mg BID | 14.8 |
| Placebo-Apremilast 30 mg BID | 11.1 |
"The primary efficacy measure was a Global Response Assessment (GRA), a subject completed questionnaire that measures improvement in overall symptoms. The GRA is a 7-point scale the allows the subject to respond to the question: As compared to when you started the study, overall how do you feel? The responses are: Markedly Improved - 7, Moderately Improved - 6, Mildly Improved - 5, Same - 4, Mildly Worse - 3, Moderately Worse - 2, Markedly Worse - 1.~The primary outcome showing response to treatment was the number of subjects that were moderately or markedly improved on the GRA scale." (NCT00814632)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|---|
| Study Drug CC 10004 | 5 |
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers) (NCT00866359)
Timeframe: Baseline to Day 85
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo (Oral) BID | 50 |
| Apremilast 30mg (Oral) BID | 100 |
The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score. The score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement. (NCT00866359)
Timeframe: Day 1 to Day 85 or to early termination visit
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.1 |
| Apremilast 30mg (Oral) BID | -1.2 |
The number of oral ulcers were counted at Day 169 in reference to the participants' first day of active treatment (Day 1 or Day 85). (NCT00866359)
Timeframe: Day 169
| Intervention | ulcers/participant (Mean) |
|---|---|
| Placebo/Apremilast 30 mg | 0.4 |
| Apremilast 30 mg /Apremilast 30mg BID (Oral) | 0.6 |
The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline). (NCT00866359)
Timeframe: Day 197
| Intervention | ulcers/participants (Mean) |
|---|---|
| Placebo/Apremilast 30 mg | 1.6 |
| Apremilast 30 mg /Apremilast 30mg BID (Oral) | 1.7 |
The number of oral ulcers were counted at each visit and at the end of the treatment period (starting point was at baseline). (NCT00866359)
Timeframe: Day 85
| Intervention | ulcers/participants (Least Squares Mean) |
|---|---|
| Placebo (Oral) BID | 2.0 |
| Apremilast 30mg (Oral) BID | 0.4 |
The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score. The score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement. (NCT00866359)
Timeframe: Day 1 to Day 197
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 30 mg | -0.6 |
| Apremilast 30 mg/Apremilast 30mg BID | -1.2 |
The Behçet's Disease Current Activity Index consists of three component scores, a participant's perception of disease activity, a clinician's overall perception of disease activity and a Behçet's Disease Current Activity Index Score. The score ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening) and a negative change from baseline indicates improvement. (NCT00866359)
Timeframe: Day 169
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 30 mg | 1.4 |
| Apremilast 30mg/Apremilast 30mg | 1.6 |
Area under curve (AUC^85) from Day 1 to Day 85 for the number of oral ulcers per day was determined using the trapezoidal rule and divided by the days between the date of the last observation and baseline. The AUC was determined using the LOCF approach to impute missing values. (NCT00866359)
Timeframe: Day 1 to Day 85
| Intervention | total AUC (#ulcers*days) (Least Squares Mean) |
|---|---|
| Placebo (Oral) BID | 157.82 |
| Apremilast 30mg (Oral) BID | 67.74 |
Area under curve (AUC) from Day 1 to Day 85 (AUC^85) for the number of oral plus genital ulcers per day was determined using the trapezoidal rule and divided by the days between the date of the last observation and baseline. The AUC was determined using the LOCF approach to impute missing values. (NCT00866359)
Timeframe: Day 1 to Day 85
| Intervention | total AUC (#ulcers*days) (Mean) |
|---|---|
| Placebo (Oral) BID | 193.95 |
| Apremilast 30mg (Oral) BID | 65.79 |
A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points. (NCT00866359)
Timeframe: Day 169
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 30 mg | 9.6 |
| Apremilast 30 mg /Apremilast 30mg BID (Oral) | 9.7 |
A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points. (NCT00866359)
Timeframe: Day 197
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 30 mg | 21.0 |
| Apremilast 30 mg /Apremilast 30mg BID (Oral) | 27.2 |
A Treatment Emergent Adverse Event (TEAE) was defined as any AE occurring or worsening on or after the first treatment of any study drug, and within 28 days after the last dose of the last study drug. A treatment related toxicity was considered by the investigator to be not suspected or suspected. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. (NCT00866359)
Timeframe: Day 1 to Day 85; maximum exposure to study drug was 13 weeks during treatment phase
| Intervention | participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Any TEAE | Any drug related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug related TEAE | Any TEAE leading to drug interruption | Any TEAE leading to drug withdrawal | |
| Apremilast 30mg (Oral) BID | 49 | 30 | 5 | 2 | 0 | 1 | 4 |
| Placebo (Oral) BID | 50 | 24 | 5 | 3 | 1 | 0 | 5 |
Comparison of the percentage of participants who were oral ulcer-free (complete response: free from active oral ulcers), or whose oral ulcers were reduced by ≥ 50%, (partial response) between the apremilast-treated and the placebo-treated groups. In this case, partial response also includes complete response. (NCT00866359)
Timeframe: Baseline and Day 85
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Complete Response | Partial Response | |
| Apremilast 30mg (Oral) BID | 70.9 | 89.1 |
| Placebo (Oral) BID | 28.6 | 50.0 |
A 100-mm VAS pain scale for oral ulcers was completed by the participant at timepoints specified in the protocol. Each 100-mm VAS was presented to the participant on a single sheet of bond paper. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was measured by ruler and recorded. When responding to a VAS item, participants specify their level of agreement to a statement by indicating a position along a continuous line between two end-points. (NCT00866359)
Timeframe: Day 85
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (Oral) BID | 36.7 |
| Apremilast 30mg (Oral) BID | 9.9 |
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers) (NCT00866359)
Timeframe: Day 1 to Day 197
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 30 mg | 100 |
| Apremilast 30mg/Apremilast 30mg | 100 |
The percentage of participants who were genital ulcer-free (complete response: free from active genital ulcers) (NCT00866359)
Timeframe: Day 1 to Day 169
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 30 mg | 66.7 |
| Apremilast 30mg/Apremilast 30mg | 100 |
A Treatment Emergent Adverse Event (TEAE) is as any AE occurring or worsening on or after the first treatment of any study drug, and within 28 days after the last dose of the last study drug. A treatment related toxicity was considered by the investigator to be not suspected or suspected. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. (NCT00866359)
Timeframe: Day 1 to Day 197; maximum exposure was 25.1 weeks
| Intervention | particpants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Any TEAE | Any drug related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug related TEAE | TEAE leading to drug interuption | TEAE leading to drug withdrawal | |
| Apremilast 30 mg BID/Apremilast 30mg BID (Oral) | 50 | 33 | 11 | 5 | 1 | 1 | 7 |
| Placebo BID/Apremilast 30 BID (Oral) | 39 | 20 | 1 | 1 | 0 | 0 | 1 |
"A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:~Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);~Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;~Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;~Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater;~New onset or worsening of existing Behçet Disease-related inflammatory eye disease requiring initiation of immunosuppressive therapy (uveitis)." (NCT00866359)
Timeframe: Day 1 to Day 169
| Intervention | participants (Number) | |
|---|---|---|
| Participants who experienced a disease flare | Participants with new onset or worsening uveitis | |
| Apremilast 30mg/Apremilast 30mg | 19 | 2 |
| Placebo/Apremilast 30 mg | 15 | 1 |
Sum of the number oral ulcers, genital ulcers or oral plus genital ulcers at Day 85 (NCT00866359)
Timeframe: Day 85
| Intervention | Ulcers/participants (Least Squares Mean) |
|---|---|
| Placebo (Oral) BID | 2.3 |
| Apremilast 30mg (Oral) BID | 0.6 |
"A flare was defined as the development of new manifestations of BD or worsening of existing disease, meeting the following criteria:~Organ involvement: any major organ involvement (eg, central nervous system, gastrointestinal tract);~Oral/genital ulcers: ≥ 100% increase in the number of oral or genital ulcers from Day 1 or a minimum increase of 3 in the number of oral or genital ulcers, whichever is greater;~Arthritis: ≥ 50% increase in the number of swollen joints, or a minimum increase of 3 swollen joints, whichever is greater;~Skin lesions (non-oral/genital ulcers): ≥ 50% increase in the total score of the Physician's Global Assessment of Skin Lesions, or a minimum increase of 2 in the total score of the Physician's Global Assessment of Skin Lesions, whichever is greater'~New onset or worsening of existing Behçet Disease-related inflammatory eye disease requiring initiation of immunosuppressive therapy (uveitis)." (NCT00866359)
Timeframe: Day 1 to Day 85
| Intervention | participants (Number) | |
|---|---|---|
| Participants who had disease flare | Participants with new onset or worsening uveitis | |
| Apremilast 30mg (Oral) BID | 12 | 0 |
| Placebo (Oral) BID | 27 | 3 |
(NCT00869089)
Timeframe: 24 weeks
| Intervention | participants (Number) | |
|---|---|---|
| Response to treatment | Minimal or no response to treatment | |
| CC-10004 | 0 | 2 |
Improvement in IGA (Investigator Global Assessment) by two or more points on a five point scale, with 0 being no disease activity and 5 being maximum disease activity, at week 12 (NCT00931242)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|---|
| Apremilast | 2 |
EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, edema, lichenification, and excoriations/erosions are scored on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 to 6. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. (NCT00931242)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|---|
| Apremilast | 1 |
EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, edema, lichenification, and excoriations/erosions are scored on a scale of 0 (none) to 3 (severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 to 6. The total qualitative score is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and summed to yield the EASI score. (NCT00931242)
Timeframe: 12 weeks
| Intervention | participants (Number) |
|---|---|
| Apremilast | 2 |
To evaluate the safety and tolerability of Apremilast in AS, the investigator recorded the incidence of adverse events. (NCT00944658)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 17 |
| Apremilast | 18 |
Bath Ankylosing Spondylitis Functional Index (BASFI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease. (NCT00944658)
Timeframe: Baseline and 12 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -0.28 |
| Apremilast | -1.74 |
"This endpoint the night time pain score change was recorded by questionnaire to evaluate the Apremilast effect on symptom, higher reduction better improvement.~scale is 0-10" (NCT00944658)
Timeframe: Baseline and 12 weeks
| Intervention | score on a scale (Mean) |
|---|---|
| Placebo | -0.23 |
| Apremilast | -0.81 |
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease. (NCT00944658)
Timeframe: Baseline and 12 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -0.77 |
| Apremilast | -1.59 |
(NCT01045551)
Timeframe: Week 12, Week 16
| Intervention | telangiectasia count (Mean) |
|---|---|
| Open Label Apremilast 20 mg (Twice Per Day) | 0.2000 |
Papule and pustule count consisted of direct measurement of the number of papules/pustules on the face. Papule and pustule count, compared between baseline and end of treatment Week 12 was calculated (NCT01045551)
Timeframe: Baseline to Week 12
| Intervention | papule count (Mean) |
|---|---|
| Open Label Apremilast 20 mg (Twice Per Day) | -0.2 |
physician count of telangiectasias on the face at visit 1 (baseline) compared to at visit 8 (week 12) (NCT01045551)
Timeframe: Baseline, Week 12
| Intervention | telangiectasia count (Mean) |
|---|---|
| Open Label Apremilast 20 mg (Twice Per Day) | 0 |
The change in the Physician Overall Erythema Severity. Scale range 0 - 3. 0 = none/absent, 1 = mild, 2 = moderate, 3 = severe. 0 is considered a better outcome, 3 is considered a worse outcome. (NCT01045551)
Timeframe: Baseline, Week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20 mg (Twice Per Day) | -0.7000 |
The Physician Global 7-point Assessment. Scale range: 0-7. 0 = clear, 1 = minimal, 2 = mild, 3 = mild to moderate, 4= moderate, 5= moderate to severe, 6 = severe. 0 is a better outcome, 6 is a worse outcome. No subscales were used. (NCT01045551)
Timeframe: Baseline, week 12
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20 mg (Twice Per Day) | -0.90000 |
This was an intent to treat analysis--dropouts are considered treatment failures. Missing data at 12 weeks imputed by last observation carried forward. (NCT01140503)
Timeframe: Data collected at 12 weeks after baseline visit.
| Intervention | participants (Number) |
|---|---|
| Apremilast | 1 |
The CDASI (Cutaneous Dermatomyositis Activity and Severity Index) is a validated instrument to measure skin disease activity in dermatomyositis. A clinically meaningful change is a decrease of 4 points. All missing data are imputed using last observation carried forward. Calculation is performed as the score at 12 weeks minus the score at baseline. (NCT01140503)
Timeframe: Data collected at baseline at 12 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | 6 |
(NCT01140503)
Timeframe: 16 weeks
| Intervention | adverse events (Number) |
|---|---|
| Apremilast | 12 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: •78 tender joint count, •76 swollen joint count, •Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; •Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 18.5 |
| Apremilast 20 mg | 31.0 |
| Apremilast 30 mg | 42.9 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 60.3 |
| Apremilast 20 mg | 69.5 |
| Apremilast 30 mg | 69.1 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from Baseline by ≥ 20 mm VAS. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 29.8 |
| Apremilast 20 mg | 38.7 |
| Apremilast 30 mg | 46.4 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from Baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 73.8 |
| Placebo / Apremilast 30 mg | 71.2 |
| Apremilast 20 mg | 77.5 |
| Apremilast 30 mg | 73.6 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 0.6 |
| Apremilast 20 mg | 5.4 |
| Apremilast 30 mg | 10.1 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 6.0 |
| Apremilast 20 mg | 15.5 |
| Apremilast 30 mg | 16.1 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 53.1 |
| Placebo / Apremilast 30 mg | 50.0 |
| Apremilast 20 mg | 63.0 |
| Apremilast 30 mg | 54.6 |
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 82.8 |
| Placebo / Apremilast 30 mg | 70.0 |
| Apremilast 20 mg | 75.0 |
| Apremilast 30 mg | 74.4 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 33.3 |
| Placebo / Apremilast 30 mg | 27.8 |
| Apremilast 20 mg | 50.7 |
| Apremilast 30 mg | 38.2 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 14.3 |
| Apremilast 20 mg | 31.1 |
| Apremilast 30 mg | 31.6 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.3 |
| Apremilast 20 mg | -2.0 |
| Apremilast 30 mg | -1.8 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 15.3 |
| Apremilast 20 mg | 27.2 |
| Apremilast 30 mg | 22.8 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 39.7 |
| Apremilast 20 mg | 49.2 |
| Apremilast 30 mg | 45.6 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 39.7 |
| Apremilast 20 mg | 42.4 |
| Apremilast 30 mg | 38.2 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 4.46 |
| Placebo / Apremilast 30 mg | 4.62 |
| Apremilast 20 mg | 6.98 |
| Apremilast 30 mg | 5.69 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | mm (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -20.2 |
| Placebo / Apremilast 30 mg | -21.0 |
| Apremilast 20 mg | -17.8 |
| Apremilast 30 mg | -20.3 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement." (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.12 |
| Apremilast 20 mg | 1.52 |
| Apremilast 30 mg | 3.33 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement." (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.55 |
| Apremilast 20 mg | 1.68 |
| Apremilast 30 mg | 3.88 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement." (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 4.33 |
| Placebo / Apremilast 30 mg | 4.15 |
| Apremilast 20 mg | 4.27 |
| Apremilast 30 mg | 3.67 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.20 |
| Apremilast 20 mg | -0.66 |
| Apremilast 30 mg | -0.90 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.26 |
| Apremilast 20 mg | -0.73 |
| Apremilast 30 mg | -0.79 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -1.47 |
| Placebo / Apremilast 30 mg | -1.15 |
| Apremilast 20 mg | -1.40 |
| Apremilast 30 mg | -1.31 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -0.8 |
| Placebo / Apremilast 30 mg | -2.4 |
| Apremilast 20 mg | -2.7 |
| Apremilast 30 mg | -1.8 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -15.00 |
| Placebo / Apremilast 30 mg | -14.03 |
| Apremilast 20 mg | -15.41 |
| Apremilast 30 mg | -14.54 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.45 |
| Apremilast 20 mg | 3.49 |
| Apremilast 30 mg | 5.01 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -4.2 |
| Apremilast 20 mg | -11.2 |
| Apremilast 30 mg | -14.7 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -5.7 |
| Apremilast 20 mg | -11.5 |
| Apremilast 30 mg | -13.5 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Baseline and week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -2.2 |
| Placebo / Apremilast 30 mg | -1.9 |
| Apremilast 20 mg | -2.7 |
| Apremilast 30 mg | -1.9 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.8 |
| Apremilast 20 mg | -1.6 |
| Apremilast 30 mg | -1.6 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.9 |
| Apremilast 20 mg | -1.4 |
| Apremilast 30 mg | -1.3 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.076 |
| Apremilast 20 mg | -0.211 |
| Apremilast 30 mg | -0.258 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.086 |
| Apremilast 20 mg | -0.198 |
| Apremilast 30 mg | -0.244 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -0.27 |
| Placebo / Apremilast 30 mg | -0.29 |
| Apremilast 20 mg | -0.37 |
| Apremilast 30 mg | -0.32 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 57.4 |
| Apremilast 20 mg | 66.1 |
| Apremilast 30 mg | 60.3 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.4 |
| Apremilast 20 mg | -1.9 |
| Apremilast 30 mg | -1.7 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -3.14 |
| Apremilast 20 mg | -7.55 |
| Apremilast 30 mg | -9.52 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0 to 76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -3.84 |
| Apremilast 20 mg | -8.24 |
| Apremilast 30 mg | -8.72 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.81 |
| Apremilast 20 mg | 3.50 |
| Apremilast 30 mg | 4.23 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 19.0 |
| Apremilast 20 mg | 30.4 |
| Apremilast 30 mg | 38.1 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 4.8 |
| Placebo / Apremilast 30 mg | 14.8 |
| Apremilast 20 mg | 15.4 |
| Apremilast 30 mg | 13.8 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 65.2 |
| Placebo / Apremilast 30 mg | 73.1 |
| Apremilast 20 mg | 85.4 |
| Apremilast 30 mg | 77.6 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 1.2 |
| Apremilast 20 mg | 6.0 |
| Apremilast 30 mg | 4.2 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 25.4 |
| Placebo / Apremilast 30 mg | 27.9 |
| Apremilast 20 mg | 24.8 |
| Apremilast 30 mg | 24.6 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 52.2 |
| Placebo / Apremilast 30 mg | 53.8 |
| Apremilast 20 mg | 68.8 |
| Apremilast 30 mg | 63.3 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 4.2 |
| Apremilast 20 mg | 14.3 |
| Apremilast 30 mg | 19.0 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response at Week 24. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 13.1 |
| Apremilast 20 mg | 25.6 |
| Apremilast 30 mg | 35.1 |
A Treatment Emergent Adverse Event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT01172938)
Timeframe: Week 0 to Week 16 for placebo participants who entered early escape at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Treatment Emergent Adverse Events | Drug-related TEAE | Severe TEAE | Serious TEAE (SAE) | Drug-related Serious AE) | TEAE leading to drug interruption | TEAE leading to drug withdrawal | TEAE leading to drug death | |
| Apremilast 20 mg | 101 | 54 | 8 | 8 | 0 | 10 | 10 | 1 |
| Apremilast 30 mg | 103 | 70 | 11 | 9 | 3 | 17 | 12 | 0 |
| Placebo | 81 | 32 | 6 | 7 | 2 | 9 | 8 | 0 |
A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT01172938)
Timeframe: Baseline to Week 260; median total exposure to Apremilast was 170 weeks
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Treatment Emergent Adverse Events (TEAEs) | Drug-related TEAE | Severe TEAE | Serious TEAE (SAE) | Drug-related SAE | TEAE leading to drug interruption | TEAE leading to drug withdrawal | TEAE leading to death | |
| Apremilast 20 mg (Pre-switch) | 203 | 96 | 35 | 41 | 4 | 47 | 27 | 1 |
| Apremilast 20 mg/30 mg BID (Post-switch) | 39 | 5 | 1 | 6 | 1 | 3 | 0 | 0 |
| Apremilast 30 mg BID | 131 | 131 | 30 | 49 | 9 | 49 | 30 | 2 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01172938)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 69.4 |
| Placebo / Apremilast 30 mg | 55.6 |
| Apremilast 20 mg | 84.1 |
| Apremilast 30 mg | 75.3 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 46.9 |
| Apremilast 20 mg | 58.3 |
| Apremilast 30 mg | 60.5 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 49.0 |
| Apremilast 20 mg | 56.3 |
| Apremilast 30 mg | 52.6 |
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01172938)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 29.8 |
| Apremilast 20 mg | 46.4 |
| Apremilast 30 mg | 48.8 |
EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01172938)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 16.1 |
| Apremilast 20 mg | 30.4 |
| Apremilast 30 mg | 42.3 |
The Pruritus Visual Analog Scores (VAS) were used to measure the amount of itching and discomfort a participant experiences. Participant's Assessment of Pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? All VAS values range from 0 to 100. Higher scores correspond to more severe symptom or disease. Change from baseline was calculated for the VAS scale, where change = visit value - baseline value. (NCT01194219)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Apremilast | -31.5 |
| Placebo | -7.3 |
Time to loss was the time between the re-randomization date and the date of the first assessment where loss of PASI-75 was observed (event); or the time between the re-randomization date and the date of the last PASI assessment in the Weeks 32-52 interval prior to addition of protocol-prohibited medication/therapy, or resumption of APR 30 BID, or discontinuation, or Week 52 if no loss (censored). (NCT01194219)
Timeframe: Week 32 to Week 52
| Intervention | Weeks (Median) |
|---|---|
| APR-APR-Re-randomized to APR | 17.7 |
| APR-APR -Re-randomized to PBO | 5.1 |
"BSA was a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit BSA - baseline BSA) / baseline BSA (%)." (NCT01194219)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Apremilast | -47.77 |
| Placebo | -6.99 |
Psoriasis Area Severity Index (PASI) scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. The PASI score was set to missing if any severity score or degree of involvement is missing. PASI score percent change from baseline was calculated as 100* (visit score - baseline score)/baseline score (%). (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo/Apremilast | -52.1 |
| Placebo | -16.8 |
A participant was classified as having at least a 50% improvement in PASI score from baseline, which was equivalent to a percent change from baseline ranging from -100% to -50%. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination. (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo/Apremilast | 58.7 |
| Placebo | 17.0 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing. (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast | 33.1 |
| Placebo (PBO) | 5.3 |
The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator factored in areas that have already been cleared (ie, have scores of 0) and did not just evaluate remaining lesions for severity, ie, the severity of each sign was averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score. (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 21.7 |
| Placebo | 3.9 |
PASI-75 response was the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. See Outcome Measure #1 for further description. sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See OCM #2 for further description. (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 20.3 |
| Placebo | 3.5 |
Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2]. (NCT01194219)
Timeframe: Week 0 to Week 260
| Intervention | participants (Number) | ||
|---|---|---|---|
| Participants with any psoriasis flare [1] | Participants with any psoriasis rebound [2] | PASI ≥ 125% of Baseline score after last dose [3] | |
| Apremilast | 35 | 12 | 26 |
"DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best." (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Apremilast | -6.6 |
| Placebo | -2.1 |
Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2]. (NCT01194219)
Timeframe: Weeks 0 to Week 16
| Intervention | participants (Number) | ||
|---|---|---|---|
| Participants with any psoriasis flare [1] | Participants with any psoriasis rebound [2] | PASI ≥ 125% of Baseline score after last dose [3] | |
| Apremilast | 6 | 1 | 3 |
| Placebo | 7 | 1 | 3 |
The Apremilast-exposure Period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. Adverse events that started after 28 days of initiating placebo and before resuming apremilast treatment in the Randomized Treatment Withdrawal Phase (Weeks 32 to 52) were excluded in the Apremilast-exposure Period. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT01194219)
Timeframe: Week 0 to Week 260; mean exposure to apremilast 30 mg BID during the Apremilast-exposure Period up to Week 260 was 97.83 weeks
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any At TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-Related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug withdrawal | Any TEAE Leading to Death | |
| Apremilast | 675 | 372 | 78 | 74 | 12 | 107 | 98 | 3 |
An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT01194219)
Timeframe: Week 0 to Week 16; mean duration of exposure was 14.8 weeks and 15.0 weeks for subjects randomized to placebo and apremilast respectively.
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-Related TEAE | Any TEAE leading to Drug Interruption | Any TEAE leading to drug withdrawal | Any TEAE Leading to Death | |
| Apremilast | 388 | 224 | 20 | 12 | 4 | 37 | 29 | 1 |
| Placebo | 157 | 58 | 9 | 8 | 0 | 13 | 9 | 1 |
The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value. (NCT01194219)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Apremilast | 2.28 |
| Placebo | -0.81 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -1.18 |
| Placebo / Apremilast 30 mg | -1.18 |
| Apremilast 20 mg | -1.11 |
| Apremilast 30 mg | -1.30 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: - 28 tender joint count - 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; - C-reactive protein (CRP) - Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.27 |
| Apremilast 20 mg | -0.74 |
| Apremilast 30 mg | -0.67 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.27 |
| Apremilast 20 mg | -0.73 |
| Apremilast 30 mg | -0.65 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 1.97 |
| Placebo / Apremilast 30 mg | 4.95 |
| Apremilast 20 mg | 2.45 |
| Apremilast 30 mg | 4.38 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.63 |
| Apremilast 20 mg | 0.91 |
| Apremilast 30 mg | 2.75 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.52 |
| Apremilast 20 mg | 0.68 |
| Apremilast 30 mg | 2.65 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | mm (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -15.6 |
| Placebo / Apremilast 30 mg | -16.0 |
| Apremilast 20 mg | -13.5 |
| Apremilast 30 mg | -12.9 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 4.13 |
| Placebo / Apremilast 30 mg | 5.97 |
| Apremilast 20 mg | 4.05 |
| Apremilast 30 mg | 4.97 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 40.9 |
| Apremilast 20 mg | 42.9 |
| Apremilast 30 mg | 41.1 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 40.9 |
| Apremilast 20 mg | 44.2 |
| Apremilast 30 mg | 46.6 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 23.1 |
| Apremilast 20 mg | 29.0 |
| Apremilast 30 mg | 20.8 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 24.0 |
| Apremilast 20 mg | 29.9 |
| Apremilast 30 mg | 22.8 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 42.5 |
| Placebo / Apremilast 30 mg | 41.0 |
| Apremilast 20 mg | 40.0 |
| Apremilast 30 mg | 37.2 |
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 70.0 |
| Placebo / Apremilast 30 mg | 64.5 |
| Apremilast 20 mg | 68.0 |
| Apremilast 30 mg | 67.5 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 53.3 |
| Placebo / Apremilast 30 mg | 47.5 |
| Apremilast 20 mg | 52.9 |
| Apremilast 30 mg | 52.6 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 5.0 |
| Apremilast 20 mg | 14.7 |
| Apremilast 30 mg | 10.5 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 3.1 |
| Apremilast 20 mg | 5.5 |
| Apremilast 30 mg | 2.5 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 78.3 |
| Placebo / Apremilast 30 mg | 73.3 |
| Apremilast 20 mg | 72.4 |
| Apremilast 30 mg | 74.6 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: - 78 tender joint count, - 76 swollen joint count, - Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; - Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 33.3 |
| Apremilast 20 mg | 47.9 |
| Apremilast 30 mg | 48.1 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 15.7 |
| Apremilast 20 mg | 31.3 |
| Apremilast 30 mg | 24.7 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 8.8 |
| Apremilast 20 mg | 14.1 |
| Apremilast 30 mg | 11.7 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 30.5 |
| Placebo / Apremilast 30 mg | 27.4 |
| Apremilast 20 mg | 26.7 |
| Apremilast 30 mg | 18.6 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); o Patient's global assessment of disease activity (measured on a 100 mm VAS); o Physician's global assessment of disease activity (measured on a 100 mm VAS); o Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); o C-Reactive Protein. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 0.6 |
| Apremilast 20 mg | 3.7 |
| Apremilast 30 mg | 1.2 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 16.9 |
| Placebo / Apremilast 30 mg | 14.3 |
| Apremilast 20 mg | 9.8 |
| Apremilast 30 mg | 6.8 |
Percentage of participants with an ACR20 response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 18.9 |
| Apremilast 20 mg | 37.4 |
| Apremilast 30 mg | 32.1 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 59.1 |
| Apremilast 20 mg | 62.3 |
| Apremilast 30 mg | 61.6 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 62.1 |
| Apremilast 20 mg | 68.8 |
| Apremilast 30 mg | 68.5 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 95.7 |
| Placebo / Apremilast 30 mg | 88.9 |
| Apremilast 20 mg | 80.7 |
| Apremilast 30 mg | 85.0 |
EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 21.4 |
| Apremilast 20 mg | 41.7 |
| Apremilast 30 mg | 33.3 |
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 31.4 |
| Apremilast 20 mg | 53.4 |
| Apremilast 30 mg | 48.8 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 52.9 |
| Apremilast 20 mg | 54.2 |
| Apremilast 30 mg | 56.4 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 51.0 |
| Apremilast 20 mg | 57.0 |
| Apremilast 30 mg | 57.4 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 72.5 |
| Placebo / Apremilast 30 mg | 79.5 |
| Apremilast 20 mg | 70.0 |
| Apremilast 30 mg | 69.2 |
"A treatment emergent adverse event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). The severity of each adverse event (AE) and serious AE (SAE) was assessed by the investigator and graded based on a scale from Mild - mild symptoms to Severe AEs (non-serious or serious). A serious adverse event (SAE) is any AE which:~Resulted in death~Was life-threatening~Required inpatient hospitalization or prolongation of existing hospitalization~Resulted in persistent or significant disability/incapacity~Was a congenital anomaly/birth defect~Constituted an important medical event" (NCT01212757)
Timeframe: Week 0 to week 260; overall median duration of exposure to apremilast 20 mg and 30 mg BID was 198 weeks
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 20 mg (Pre-switch) | 202 | 102 | 35 | 41 | 6 | 47 | 24 | 0 |
| Apremilast 20 mg/30 mg (Post-switch) | 53 | 5 | 2 | 5 | 1 | 4 | 3 | 0 |
| Apremilast 30 mg BID | 207 | 100 | 37 | 41 | 6 | 65 | 30 | 2 |
"A treatment emergent adverse event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). The severity of each adverse event (AE) and serious AE (SAE) was assessed by the investigator and graded based on a scale from Mild - mild symptoms to Severe AEs (non-serious or serious). A serious adverse event (SAE) is any AE which:~Resulted in death~Was life-threatening~Required inpatient hospitalization or prolongation of existing hospitalization~Resulted in persistent or significant disability/incapacity~Was a congenital anomaly/birth defect~Constituted an important medical event" (NCT01212757)
Timeframe: Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
| Intervention | Participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE (SAE) | Any Drug-Related SAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 20 mg | 106 | 53 | 3 | 6 | 3 | 16 | 5 | 0 |
| Apremilast 30 mg | 96 | 57 | 11 | 4 | 1 | 31 | 12 | 0 |
| Placebo | 72 | 28 | 5 | 3 | 0 | 11 | 3 | 0 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212757)
Timeframe: Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 78.3 |
| Placebo / Apremilast 30 mg | 77.8 |
| Apremilast 20 mg | 57.9 |
| Apremilast 30 mg | 65.0 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -8.0 |
| Apremilast 20 mg | -11.5 |
| Apremilast 30 mg | -9.7 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.44 |
| Apremilast 20 mg | 2.97 |
| Apremilast 30 mg | 3.30 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.81 |
| Apremilast 20 mg | 2.17 |
| Apremilast 30 mg | 2.91 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 24.5 |
| Apremilast 20 mg | 39.9 |
| Apremilast 30 mg | 32.1 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: - 28 tender joint count (TJC), - 28 swollen joint count (SJC), - Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; - Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -3.30 |
| Apremilast 20 mg | -7.75 |
| Apremilast 30 mg | -6.81 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -3.21 |
| Apremilast 20 mg | -7.71 |
| Apremilast 30 mg | -6.35 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.1 |
| Apremilast 20 mg | -0.8 |
| Apremilast 30 mg | -1.3 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.1 |
| Apremilast 20 mg | -0.9 |
| Apremilast 30 mg | -1.4 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -0.208 |
| Placebo / Apremilast 30 mg | -0.310 |
| Apremilast 20 mg | -0.192 |
| Apremilast 30 mg | -0.330 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.053 |
| Apremilast 20 mg | -0.157 |
| Apremilast 30 mg | -0.193 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.085 |
| Apremilast 20 mg | -0.165 |
| Apremilast 30 mg | -0.206 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.0 |
| Apremilast 20 mg | -0.9 |
| Apremilast 30 mg | -1.4 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.9 |
| Apremilast 20 mg | -0.9 |
| Apremilast 30 mg | -1.3 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -2.5 |
| Placebo / Apremilast 30 mg | -2.5 |
| Apremilast 20 mg | -1.7 |
| Apremilast 30 mg | -2.1 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01212757)
Timeframe: Baseline and Week 16
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -7.0 |
| Apremilast 20 mg | -12.5 |
| Apremilast 30 mg | -11.9 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -13.66 |
| Placebo / Apremilast 30 mg | -13.13 |
| Apremilast 20 mg | -12.03 |
| Apremilast 30 mg | -14.38 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212757)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -1.9 |
| Placebo / Apremilast 30 mg | -2.1 |
| Apremilast 20 mg | -1.8 |
| Apremilast 30 mg | -1.8 |
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain. (NCT01212770)
Timeframe: Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 121.71 weeks and 232.50 weeks for apremilast 30 mg BID
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE (SAE) | Any Serious Drug-Related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to death | |
| Apremilast 20 mg (Pre-switch) | 194 | 98 | 21 | 38 | 5 | 48 | 30 | 0 |
| Apremilast 20/30 mg (Post-switch) | 64 | 11 | 0 | 4 | 0 | 4 | 0 | 1 |
| Apremilast 30 mg | 209 | 111 | 30 | 54 | 3 | 53 | 30 | 0 |
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain. (NCT01212770)
Timeframe: Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE (SAE) | Any Serious Drug-Related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 20 mg | 100 | 50 | 5 | 3 | 0 | 20 | 13 | 0 |
| Apremilast 30 mg | 104 | 62 | 10 | 6 | 0 | 16 | 12 | 0 |
| Placebo | 83 | 33 | 8 | 9 | 2 | 4 | 10 | 0 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 73.5 |
| Placebo / Apremilast 30 mg | 75.0 |
| Apremilast 20 mg | 77.3 |
| Apremilast 30 mg | 71.3 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 51.4 |
| Apremilast 20 mg | 51.5 |
| Apremilast 30 mg | 54.5 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 53.2 |
| Apremilast 20 mg | 48.5 |
| Apremilast 30 mg | 54.5 |
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 29.0 |
| Apremilast 20 mg | 40.2 |
| Apremilast 30 mg | 51.5 |
EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 20.1 |
| Apremilast 20 mg | 32.0 |
| Apremilast 30 mg | 42.5 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 95.5 |
| Placebo / Apremilast 30 mg | 92.3 |
| Apremilast 20 mg | 88.5 |
| Apremilast 30 mg | 91.8 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 60.6 |
| Apremilast 20 mg | 67.6 |
| Apremilast 30 mg | 73.8 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 59.2 |
| Apremilast 20 mg | 66.2 |
| Apremilast 30 mg | 71.3 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 18.3 |
| Apremilast 20 mg | 28.4 |
| Apremilast 30 mg | 40.7 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 20.8 |
| Placebo / Apremilast 30 mg | 14.9 |
| Apremilast 20 mg | 9.2 |
| Apremilast 30 mg | 10.4 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 2.4 |
| Apremilast 20 mg | 4.7 |
| Apremilast 30 mg | 3.6 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 28.3 |
| Placebo / Apremilast 30 mg | 31.8 |
| Apremilast 20 mg | 25.2 |
| Apremilast 30 mg | 30.2 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 7.7 |
| Apremilast 20 mg | 13.6 |
| Apremilast 30 mg | 16.2 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 59.3 |
| Placebo / Apremilast 30 mg | 58.2 |
| Apremilast 20 mg | 56.0 |
| Apremilast 30 mg | 63.0 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 15.4 |
| Apremilast 20 mg | 26.6 |
| Apremilast 30 mg | 31.1 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 23.1 |
| Apremilast 20 mg | 32.0 |
| Apremilast 30 mg | 44.3 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 27.2 |
| Apremilast 20 mg | 37.9 |
| Apremilast 30 mg | 52.7 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 81.1 |
| Placebo / Apremilast 30 mg | 75.8 |
| Apremilast 20 mg | 71.6 |
| Apremilast 30 mg | 79.0 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 3.6 |
| Apremilast 20 mg | 4.1 |
| Apremilast 30 mg | 5.4 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 8.3 |
| Apremilast 20 mg | 12.4 |
| Apremilast 30 mg | 15.0 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 44.1 |
| Placebo / Apremilast 30 mg | 43.8 |
| Apremilast 20 mg | 33.3 |
| Apremilast 30 mg | 36.8 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 28.4 |
| Apremilast 20 mg | 20.6 |
| Apremilast 30 mg | 27.7 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 24.8 |
| Apremilast 20 mg | 19.6 |
| Apremilast 30 mg | 20.5 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 68.2 |
| Placebo / Apremilast 30 mg | 80.8 |
| Apremilast 20 mg | 75.0 |
| Apremilast 30 mg | 68.9 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 36.6 |
| Apremilast 20 mg | 45.1 |
| Apremilast 30 mg | 46.3 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 35.2 |
| Apremilast 20 mg | 40.8 |
| Apremilast 30 mg | 41.3 |
The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 52 weeks. The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 33.3 |
| Placebo / Apremilast 30 mg | 28.6 |
| Apremilast 20 mg | 28.6 |
| Apremilast 30 mg | 39.1 |
The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 24 weeks of treatment. The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 11.2 |
| Apremilast 20 mg | 22.2 |
| Apremilast 30 mg | 25.6 |
The percentage of participants with Baseline psoriasis body surface area (BSA) involvement ≥ 3% who achieved 75% or greater improvement from Baseline in Psoriasis Area and Severity Index (PASI) score after 16 weeks of treatment. The Psoriasis Area and Severity Index (PASI) score is a combination of the intensity of psoriasis, assessed by erythema (reddening), induration (plaque thickness) and desquamation (scaling) scored on a scale from 0 (none) to 4 (very severe), together with the percentage of the area affected, rated on a scale from 0 (no involvement) to 6 (90% to 100% involvement). PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 7.9 |
| Apremilast 20 mg | 20.9 |
| Apremilast 30 mg | 22.2 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 7.76 |
| Placebo / Apremilast 30 mg | 6.87 |
| Apremilast 20 mg | 5.68 |
| Apremilast 30 mg | 5.87 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | mm (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -19.9 |
| Placebo / Apremilast 30 mg | -19.1 |
| Apremilast 20 mg | -14.9 |
| Apremilast 30 mg | -18.7 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.83 |
| Apremilast 20 mg | 2.01 |
| Apremilast 30 mg | 3.27 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue." (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.18 |
| Apremilast 20 mg | 1.86 |
| Apremilast 30 mg | 3.72 |
A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 64.8 |
| Placebo / Apremilast 30 mg | 73.1 |
| Apremilast 20 mg | 69.4 |
| Apremilast 30 mg | 74.8 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.7 |
| Apremilast 20 mg | -0.7 |
| Apremilast 30 mg | -1.0 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -4.9 |
| Apremilast 20 mg | -8.6 |
| Apremilast 30 mg | -12.7 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01212770)
Timeframe: Baseline and week 24
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -4.4 |
| Apremilast 20 mg | -8.2 |
| Apremilast 30 mg | -10.9 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: •28 tender joint count (TJC), •28 swollen joint count (SJC), •Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; •Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -13.54 |
| Placebo / Apremilast 30 mg | -12.38 |
| Apremilast 20 mg | -12.86 |
| Apremilast 30 mg | -14.14 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -3.1 |
| Placebo / Apremilast 30 mg | -3.8 |
| Apremilast 20 mg | -2.9 |
| Apremilast 30 mg | -3.6 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: •28 tender joint count •28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; •C-reactive protein (CRP) •Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -1.28 |
| Placebo / Apremilast 30 mg | -1.29 |
| Apremilast 20 mg | -1.21 |
| Apremilast 30 mg | -1.41 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.28 |
| Apremilast 20 mg | -0.54 |
| Apremilast 30 mg | -0.74 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.27 |
| Apremilast 20 mg | -0.57 |
| Apremilast 30 mg | -0.75 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 6.72 |
| Placebo / Apremilast 30 mg | 5.66 |
| Apremilast 20 mg | 4.78 |
| Apremilast 30 mg | 6.20 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -2.53 |
| Apremilast 20 mg | -5.18 |
| Apremilast 30 mg | -7.81 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Baseline and week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.7 |
| Apremilast 20 mg | -1.0 |
| Apremilast 30 mg | -1.1 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -2.5 |
| Placebo / Apremilast 30 mg | -2.2 |
| Apremilast 20 mg | -2.2 |
| Apremilast 30 mg | -1.9 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.14 |
| Apremilast 20 mg | 2.29 |
| Apremilast 30 mg | 3.47 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.03 |
| Apremilast 20 mg | 2.71 |
| Apremilast 30 mg | 3.37 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -2.76 |
| Apremilast 20 mg | -4.61 |
| Apremilast 30 mg | -7.70 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.3 |
| Apremilast 20 mg | -1.7 |
| Apremilast 30 mg | -2.1 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.3 |
| Apremilast 20 mg | -1.7 |
| Apremilast 30 mg | -2.3 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01212770)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -0.34 |
| Placebo / Apremilast 30 mg | -0.34 |
| Apremilast 20 mg | -0.33 |
| Apremilast 30 mg | -0.35 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01212770)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.065 |
| Apremilast 20 mg | -0.131 |
| Apremilast 30 mg | -0.192 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01212770)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.053 |
| Apremilast 20 mg | -0.137 |
| Apremilast 30 mg | -0.192 |
The Apremilast-exposure Period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. Adverse events that started after 28 days of initiating placebo and before resuming apremilast treatment in the Randomized Treatment Withdrawal Phase (Weeks 32 to 52) were excluded in the Apremilast-exposure phase. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT01232283)
Timeframe: Week 0 to Week 260; The mean duration of exposure was 100.66 weeks.
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-Related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast | 316 | 165 | 58 | 44 | 8 | 56 | 45 | 1 |
The Pruritus Visual Analog Scores (VAS) were used to measure the amount of itching and discomfort a participant experiences. Participant's Assessment of Pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? All VAS values range from 0 to 100. Higher scores correspond to more severe symptom or disease. Change from baseline was calculated for the VAS scale, where change = visit value - baseline value. (NCT01232283)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Apremilast | -33.5 |
| Placebo | -12.2 |
An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT01232283)
Timeframe: Baseline to Week 16
| Intervention | participants (Number) | |||||
|---|---|---|---|---|---|---|
| Any TEAE | Any drug related TEAE | Any Severe TEAE | Any Serious TEAE | Any TEAE leading to drug interruption | Any TEAE leading to drug withdrawal | |
| Apremilast | 185 | 106 | 12 | 5 | 16 | 15 |
| Placebo | 82 | 29 | 6 | 3 | 4 | 7 |
Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2]. (NCT01232283)
Timeframe: Week 0 to Week 16
| Intervention | participants (Number) | ||
|---|---|---|---|
| Participants with any psoriasis flare | Participants with any psoriasis rebound | PASI ≥ 125% of Baseline score after last dose | |
| Apremilast | 3 | 1 | 1 |
| Placebo | 7 | 0 | 2 |
Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2]. (NCT01232283)
Timeframe: Week 0 to Week 260
| Intervention | participants (Number) | ||
|---|---|---|---|
| Participants with any psoriasis flare | Participants with any psoriasis rebound | PASI ≥ 125% of Baseline score after last dose | |
| Apremilast | 25 | 11 | 12 |
Time to loss was the time between the re-randomization date and the date of the first assessment with loss of 50% PASI improvement (event), or the time between the re-randomization date and the date of the last PASI assessment in the randomized withdrawal phase prior to addition of topical/phototherapy or other effective psoriasis therapies, or resumption of apremilast 30 mg BID, or discontinuation, or Week 52 if no loss (censored), whichever was earlier (NCT01232283)
Timeframe: Weeks 32 to Week 52
| Intervention | Weeks (Median) |
|---|---|
| APR-APR Re-randomized to PBO | 12.4 |
| APR-APR-Re-randomized to APR | 21.9 |
"PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. See Outcome measure #1 for further description.~sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See Outcome Measure #2 for further description." (NCT01232283)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 18.6 |
| Placebo | 4.4 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at week 16. The improvement in PASI score was used as a measure of efficacy. The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing. (NCT01232283)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 28.8 |
| Placebo | 5.8 |
The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator must have factored in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign was averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score. (NCT01232283)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 20.4 |
| Placebo | 4.4 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing. (NCT01232283)
Timeframe: Baseline and Week 16
| Intervention | Percentage of Participants (Number) |
|---|---|
| Apremilast | 55.5 |
| Placebo | 19.7 |
Psoriasis Area Severity Index (PASI) scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. The PASI score was set to missing if any severity score or degree of involvement is missing. (NCT01232283)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Apremilast | -50.8 |
| Placebo | -16.0 |
"BSA was a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area.~BSA percent change from baseline (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit BSA - baseline BSA) / baseline BSA (%)." (NCT01232283)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Apremilast | -48.40 |
| Placebo | -6.25 |
"The SF-36 was a 36-item general health instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS).~Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value." (NCT01232283)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Apremilast | 2.60 |
| Placebo | -0.03 |
"DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the subject is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score was derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best." (NCT01232283)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Apremilast | -6.7 |
| Placebo | -2.7 |
"C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific marker for disease." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 41.99 |
| Apremilast 20 mg | 46.69 |
| Apremilast 30 mg | 100.04 |
"C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific marker for disease." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 39.14 |
| Apremilast 20 mg | 47.43 |
| Apremilast 30 mg | 106.22 |
"C-Reactive Protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. An elevated CRP level is identified with blood tests and is considered a non-specific marker for disease." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | 13.34 |
| Placebo/Apremilast 20 mg XO | 82.14 |
| Apremilast 20 mg | 104.25 |
| Apremilast 30 mg | 79.33 |
"The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents lowest disease activity, and the right-hand boundary (score = 100 mm) represents highest disease activity. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -28.82 |
| Apremilast 20 mg | -28.22 |
| Apremilast 30 mg | -32.66 |
"The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents lowest disease activity, and the right-hand boundary (score = 100 mm) represents highest disease activity. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -29.98 |
| Apremilast 20 mg | -24.13 |
| Apremilast 30 mg | -31.78 |
"The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 30.50 |
| Apremilast 20 mg | -5.03 |
| Apremilast 30 mg | -7.87 |
"The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 28.16 |
| Apremilast 20 mg | -6.66 |
| Apremilast 30 mg | -9.66 |
"The Subject Assessment of Pain was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | 44.63 |
| Placebo/Apremilast 20 mg XO | 15.78 |
| Apremilast 20 mg | -11.69 |
| Apremilast 30 mg | -3.73 |
"The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents lowest disease activity, and the right-hand boundary (score = 100 mm) represents highest disease activity. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 10.84 |
| Apremilast 20 mg | -3.50 |
| Apremilast 30 mg | 11.19 |
"The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents lowest disease activity, and the right-hand boundary (score = 100 mm) represents highest disease activity. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 15.04 |
| Apremilast 20 mg | 0.70 |
| Apremilast 30 mg | 2.54 |
"The Subject Global Assessment of Disease Activity was measured asking the participant to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents lowest disease activity, and the right-hand boundary (score = 100 mm) represents highest disease activity. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20 EE | 14.20 |
| Placebo / Apremilast 20 mg XO | 33.31 |
| Apremilast 20 mg | -5.20 |
| Apremilast 30 mg | 8.22 |
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal. (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -36.96 |
| Apremilast 20 mg | -34.38 |
| Apremilast 30 mg | -40.22 |
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal. (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -34.41 |
| Apremilast 20 mg | -32.56 |
| Apremilast 30 mg | -41.43 |
Joint swelling is soft tissue swelling that is detectable along the joint margins and is assessed by inspection and direct palpation of the joint, by the examiner. The ACR 66 swollen joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal interphalangeal; lower: knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal. (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -59.40 |
| Placebo/Apremilast 20 mg XO | -67.73 |
| Apremilast 20 mg | -57.31 |
| Apremilast 30 mg | -66.74 |
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal. (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -33.08 |
| Apremilast 20 mg | -26.92 |
| Apremilast 30 mg | -33.68 |
"Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 20% improvement in 68 tender joint count;~≥ 20% improvement in 66 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 47.8 |
| Placebo/Apremilast 20 mg XO | 51.3 |
| Apremilast 20 mg | 30.9 |
| Apremilast 30 mg | 38.2 |
"Percentage of participants with an American College of Rheumatology 50% Improvement (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 50% improvement in 68 tender joint count;~≥ 50% improvement in 66 swollen joint count; and~≥ 50% improvement in at least 3 of the 5 following parameters:~Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 11.4 |
| Apremilast 20 mg | 4.9 |
| Apremilast 30 mg | 9.2 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 20.3 |
| Apremilast 20 mg | 25.6 |
| Apremilast 30 mg | 32.9 |
"Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 50% improvement in 68 tender joint count;~≥ 50% improvement in 66 swollen joint count; and~≥ 50% improvement in at least 3 of the 5 following parameters:~Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 6.3 |
| Apremilast 20 mg | 4.9 |
| Apremilast 30 mg | 15.8 |
"Percentage of participants with an American College of Rheumatology 50% Improvement (ACR 50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 50% improvement in 68 tender joint count;~≥ 50% improvement in 66 swollen joint count; and~≥ 50% improvement in at least 3 of the 5 following parameters:~Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 3.4 |
| Placebo/Apremilast 20 mg XO | 11.9 |
| Apremilast 20 mg | 4.9 |
| Apremilast 30 mg | 5.3 |
"Percentage of participants with an American College of Rheumatology 70% Improvement (ACR70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:~≥ 70% improvement in 68 tender joint count;~≥ 70% improvement in 66 swollen joint count; and~≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein" (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent of participants (Number) |
|---|---|
| Placebo | 2.5 |
| Apremilast 20 mg | 1.2 |
| Apremilast 30 mg | 0.0 |
"Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 70% improvement in 68 tender joint count;~≥ 70% improvement in 66 swollen joint count; and~≥ 70% improvement in at least 3 of the 5 following parameters:~Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [(HAQ-DI)]); C-Reactive Protein." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 3.8 |
| Apremilast 20 mg | 2.4 |
| Apremilast 30 mg | 5.3 |
"Percentage of participants with an American College of Rheumatology 70% Improvement (ACR 70) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:~≥ 70% improvement in 68 tender joint count;~≥ 70% improvement in 66 swollen joint count; and~≥ 70% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein" (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 0.0 |
| Placebo/Apremilast 20 mg XO | 5.0 |
| Apremilast 20 mg | 7.1 |
| Apremilast 30 mg | 5.5 |
"The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.~The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20 EE | -6.28 |
| Placebo / Apremilast 20 mg XO | 17.15 |
| Apremilast 20 mg | 4.83 |
| Apremilast 30 mg | -15.99 |
"EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.~Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2" (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 46.8 |
| Apremilast 20 mg | 41.5 |
| Apremilast 30 mg | 44.7 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 41.7 |
| Placebo/Apremilast 20 mg XO | 61.5 |
| Apremilast 20 mg | 45.5 |
| Apremilast 30 mg | 40.0 |
"The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.~A positive change from baseline score indicates an improvement." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 39.2 |
| Apremilast 20 mg | 35.4 |
| Apremilast 30 mg | 42.1 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 39.2 |
| Apremilast 20 mg | 35.4 |
| Apremilast 30 mg | 52.6 |
"The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:~28 tender joint count (TJC),~28 swollen joint count (SJC),~Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;~Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.~The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:~Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22" (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -16.22 |
| Placebo/Apremilast 20 mg XO | -20.70 |
| Apremilast 20 mg | -14.77 |
| Apremilast 30 mg | -17.68 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.~A positive change from baseline score indicates an improvement." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 26.6 |
| Apremilast 20 mg | 14.6 |
| Apremilast 30 mg | 26.3 |
"The DAS28 measures the severity of disease at a specific time and is derived from the following variables:~28 tender joint count (TJC28)~28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;~C-reactive protein (CRP)~Subject's global assessment of disease activity (SGA )~DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.~A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.90 |
| Apremilast 20 mg | -0.73 |
| Apremilast 30 mg | -0.90 |
"The Physician Global Assessment of Disease Activity was measured asking the physician to assess the subject's current arthritis disease activity by placing a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents lowest disease activity, and the right-hand boundary (score = 100 mm) represents highest disease activity. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -41.30 |
| Placebo/Apremilast 20 mg XO | -49.10 |
| Apremilast 20 mg | -41.19 |
| Apremilast 30 mg | -44.85 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 58.3 |
| Placebo/Apremilast 20 mg XO | 43.6 |
| Apremilast 20 mg | 40.0 |
| Apremilast 30 mg | 58.2 |
"The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.~A positive change from baseline score indicates an improvement." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | 3.50 |
| Placebo/Apremilast 20 mg XO | 3.18 |
| Apremilast 20 mg | 2.87 |
| Apremilast 30 mg | 3.47 |
"The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.~A positive change from baseline score indicates an improvement." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 2.7 |
| Apremilast 20 mg | 1.5 |
| Apremilast 30 mg | 2.6 |
"The FACIT-Fatigue scale was a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue.~A positive change from baseline score indicates an improvement." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.7 |
| Apremilast 20 mg | 0.5 |
| Apremilast 30 mg | 3.4 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments. Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | 1.48 |
| Apremilast 20 mg | 1.64 |
| Apremilast 30 mg | 3.33 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.78 |
| Apremilast 20 mg | 1.66 |
| Apremilast 30 mg | 3.76 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | 2.11 |
| Placebo/Apremilast 20 mg XO | 3.50 |
| Apremilast 20 mg | 2.56 |
| Apremilast 30 mg | 5.23 |
"The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.~The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 6.81 |
| Apremilast 20 mg | 13.98 |
| Apremilast 30 mg | -9.39 |
"The erythrocyte sedimentation rate (ESR) is a blood test that can reveal inflammatory activity. The subject's blood is placed in a tall, thin tube, red erythrocytes gradually settle to the bottom. Inflammation can cause the cells to clump together. Because these clumps of cells are denser than individual cells, they settle to the bottom more quickly.~The ESR test measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -0.06 |
| Apremilast 20 mg | 11.99 |
| Apremilast 30 mg | -6.60 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -13.32 |
| Placebo/Apremilast 20 mg XO | -10.53 |
| Apremilast 20 mg | -8.20 |
| Apremilast 30 mg | -22.46 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -9.43 |
| Apremilast 20 mg | -3.50 |
| Apremilast 30 mg | -10.20 |
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal. (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -55.47 |
| Placebo/Apremilast 20 mg XO | -62.70 |
| Apremilast 20 mg | -43.88 |
| Apremilast 30 mg | -54.03 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -6.59 |
| Apremilast 20 mg | -5.01 |
| Apremilast 30 mg | -12.30 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -0.069 |
| Apremilast 20 mg | -0.080 |
| Apremilast 30 mg | -0.227 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -0.219 |
| Placebo/Apremilast 20 mg XO | -0.192 |
| Apremilast 20 mg | -0.155 |
| Apremilast 30 mg | -0.277 |
The Health Assessment Questionnaire - Disability Index (HAQ-DI) was a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -0.106 |
| Apremilast 20 mg | -0.114 |
| Apremilast 30 mg | -0.209 |
"The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:~28 tender joint count (TJC),~28 swollen joint count (SJC),~Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;~Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.~The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:~Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22" (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -11.52 |
| Apremilast 20 mg | -9.49 |
| Apremilast 30 mg | -11.38 |
"The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:~28 tender joint count (TJC),~28 swollen joint count (SJC),~Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;~Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.~The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:~Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22" (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -10.40 |
| Apremilast 20 mg | -9.46 |
| Apremilast 30 mg | -11.63 |
Joint tenderness is the presence of pain in a joint when pressure is applied by the examiner to elicit tenderness. The 68 tender joint count evaluates the following joints: upper-temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, meta-carpophalangeal, proximal interphalangeal and distal interphalangeal; lower: hip, knee, ankle, midtarsal, metatarsophalangeal and proximal interphalangeal. (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -30.81 |
| Apremilast 20 mg | -26.21 |
| Apremilast 30 mg | -27.80 |
"The DAS28 measures the severity of disease at a specific time and is derived from the following variables:~28 tender joint count~28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;~C-reactive protein (CRP)~Subject's Global Assessment of Disease Activity.~DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.~A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission." (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.82 |
| Apremilast 20 mg | -0.78 |
| Apremilast 30 mg | -0.91 |
"The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:~28 tender joint count (TJC),~28 swollen joint count (SJC),~Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;~Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.~The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:~Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22" (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 17.7 |
| Apremilast 20 mg | 12.2 |
| Apremilast 30 mg | 10.5 |
"The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:~28 tender joint count (TJC),~28 swollen joint count (SJC),~Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest;~Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.~The CDAI score ranges from 0-76 where lower scores indicate less disease activity.The following thresholds of disease activity have been defined for the CDAI:~Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22" (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 16.5 |
| Apremilast 20 mg | 12.2 |
| Apremilast 30 mg | 21.1 |
"The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the:~28 tender joint count (TJC),~28 swollen joint count (SJC),~Subject's Global Assessment of Disease Activity measured on a 100 mm visual analog scale (VAS),, where 0 mm = lowest disease activity and 100 mm = highest;~Physician's Global Assessment of Disease Activity -measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.~The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI:~Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22" (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 16.7 |
| Placebo/Apremilast 20 mg XO | 41.0 |
| Apremilast 20 mg | 25.0 |
| Apremilast 30 mg | 27.3 |
"EULAR response criteria classify each participant as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.~Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2" (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 40.5 |
| Apremilast 20 mg | 29.3 |
| Apremilast 30 mg | 35.5 |
"The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease.~Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2" (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo/Apremilast 20mg EE | 69.6 |
| Placebo/Apremilast 20 mg XO | 82.1 |
| Apremilast 20 mg | 63.0 |
| Apremilast 30 mg | 65.5 |
"Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 20% improvement in 68 tender joint count;~≥ 20% improvement in 66 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein." (NCT01285310)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 35.4 |
| Apremilast 20 mg | 28 |
| Apremilast 30 mg | 34.2 |
"Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met:~≥ 20% improvement in 68 tender joint count;~≥ 20% improvement in 66 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index ([HAQ-DI]); C-Reactive Protein" (NCT01285310)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 24.1 |
| Apremilast 20 mg | 19.5 |
| Apremilast 30 mg | 27.6 |
"The DAS28 measures the severity of disease at a specific time and is derived from the following variables:~28 tender joint count (TJC28)~28 swollen joint count (SJC28), which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee;~C-reactive protein (CRP)~Subject's global assessment of disease activity (SGA).~DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity.~A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission." (NCT01285310)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo/Apremilast 20mg EE | -1.18 |
| Placebo/Apremilast 20 mg XO | -1.68 |
| Apremilast 20 mg | -1.10 |
| Apremilast 30 mg | -1.38 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22 (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.98 |
| Apremilast 20 mg | -6.89 |
| Apremilast 30 mg | -7.63 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -2.23 |
| Apremilast 20 mg | -7.30 |
| Apremilast 30 mg | -7.36 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01307423)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.0 |
| Apremilast 20 mg | -1.9 |
| Apremilast 30 mg | -1.7 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.0 |
| Apremilast 20 mg | -2.0 |
| Apremilast 30 mg | -1.7 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.22 |
| Apremilast 20 mg | -0.69 |
| Apremilast 30 mg | -0.68 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -0.21 |
| Placebo / Apremilast 30 mg | -0.25 |
| Apremilast 20 mg | -0.32 |
| Apremilast 30 mg | -0.39 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from baseline in the overall score indicate improvement in functional ability. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.012 |
| Apremilast 20 mg | -0.156 |
| Apremilast 30mg | -0.205 |
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative changes from Baseline in the overall score indicate improvement in functional ability. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.012 |
| Apremilast 20 mg | -0.156 |
| Apremilast 30 mg | -0.207 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.5 |
| Apremilast 20 mg | -0.5 |
| Apremilast 30 mg | -1.5 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.6 |
| Apremilast 20 mg | -0.9 |
| Apremilast 30 mg | -1.5 |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -1.7 |
| Placebo/Apremilast 30 mg | -1.8 |
| Apremilast 20 mg | -1.5 |
| Apremilast 30 mg | -1.8 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -3.8 |
| Apremilast 20 mg | -9.4 |
| Apremilast 30 mg | -9.6 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -2.6 |
| Apremilast 20 mg | -7.7 |
| Apremilast 30 mg | -10.5 |
The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: 28 tender joint count (TJC), 28 swollen joint count (SJC), Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -11.0 |
| Placebo / Apremilast 30 mg | -14.67 |
| Apremilast 20 mg | -14.32 |
| Apremilast 30 mg | -13.98 |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -2.2 |
| Placebo / Apremilast 30 mg | -2.9 |
| Apremilast 20 mg | -2.2 |
| Apremilast 30 mg | -2.9 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | -1.08 |
| Placebo / Apremilast 30 mg | -1.28 |
| Apremilast 20 mg | -1.37 |
| Apremilast 30 mg | -1.39 |
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.15 |
| Apremilast 20 mg | -0.61 |
| Apremilast 30 mg | -0.68 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 6.03 |
| Placebo / Apremilast 30 mg | 4.27 |
| Apremilast 20 mg | 2.39 |
| Apremilast 30 mg | 5.89 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.07 |
| Apremilast 20 mg | 1.19 |
| Apremilast 30 mg | 2.62 |
"The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means not at all, and 4 means very much. The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement." (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.25 |
| Apremilast 20 mg | 1.37 |
| Apremilast 30 mg | 2.58 |
"The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents no pain, and the right-hand boundary (score = 100 mm) represents pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded in millimeters." (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | mm (Mean) |
|---|---|
| Placebo/Apremilast 20 mg | -13.1 |
| Placebo / Apremilast 30 mg | -18.9 |
| Apremilast 20 mg | -15.6 |
| Apremilast 30 mg | -14.2 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo / Apremilast 20 mg | 7.76 |
| Placebo / Apremilast 30 mg | 6.87 |
| Apremilast 20 mg | 5.68 |
| Apremilast 30 mg | 5.87 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 35.6 |
| Apremilast 20 mg | 46.1 |
| Apremilast 30 mg | 40.5 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 22.6 |
| Apremilast 20 mg | 29.1 |
| Apremilast 30 mg | 37.8 |
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. A Good response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 A Moderate Response is defined as either: an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Two-sided 95% confidence interval is based on the Clopper-Pearson method (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 64.5 |
| Placebo / Apremilast 30 mg | 73.5 |
| Apremilast 20 mg | 75.4 |
| Apremilast 30 mg | 79.0 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 46.1 |
| Apremilast 20 mg | 48.7 |
| Apremilast 30 mg | 63.1 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 20% improvement in 78 tender joint count; ≥ 20% improvement in 76 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 59.7 |
| Placebo / Apremilast 30 mg | 56.7 |
| Apremilast 20 mg | 53.4 |
| Apremilast 30 mg | 58.7 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 4.5 |
| Apremilast 20 mg | 11.4 |
| Apremilast 30 mg | 11.4 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 6.3 |
| Apremilast 20 mg | 16.0 |
| Apremilast 30 mg | 12.5 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 1.1 |
| Apremilast 20 mg | 4.0 |
| Apremilast 30 mg | 4.0 |
Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 4.0 |
| Apremilast 20 mg | 4.0 |
| Apremilast 30mg | 4.5 |
Measure Description: Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 73.8 |
| Placebo / Apremilast 30 mg | 79.1 |
| Apremilast 20 mg | 75.6 |
| Apremilast 30 mg | 75.9 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 17.0 |
| Apremilast 20 mg | 36.6 |
| Apremilast 30 mg | 35.2 |
Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 13.1 |
| Apremilast 20 mg | 29.1 |
| Apremilast 30 mg | 24.4 |
Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 50% improvement in 78 tender joint count; ≥ 50% improvement in 76 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 30.6 |
| Placebo / Apremilast 30 mg | 25.4 |
| Apremilast 20 mg | 27.1 |
| Apremilast 30 mg | 31.9 |
A participant was a responder if the following 3 criteria for improvement from Baseline were met: ≥ 70% improvement in 78 tender joint count; ≥ 70% improvement in 76 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 8.2 |
| Placebo / Apremilast 30 mg | 10.3 |
| Apremilast 20 mg | 13.7 |
| Apremilast 30 mg | 18.1 |
A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: -Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); -Patient's global assessment of disease activity (measured on a 100 mm VAS); -Physician's global assessment of disease activity (measured on a 100 mm VAS); -Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); -C-Reactive Protein. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 15.9 |
| Apremilast 20mg | 28.0 |
| Apremilast 30mg | 30.7 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 60.0 |
| Apremilast 20 mg | 66.3 |
| Apremilast 30 mg | 61.9 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 57.8 |
| Apremilast 20 mg | 69.7 |
| Apremilast 30 mg | 63.1 |
The EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on th DAS-28. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2 A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 17.0 |
| Apremilast 20 mg | 34.9 |
| Apremilast 30 mg | 28.4 |
The EULAR response criteria classify each subject as a good, moderate or non-responder to treatment based on the degree of improvement from baseline and the level of disease activity at the endpoint. EULAR response is derived using the individual subject's DAS28 as the measure of severity of disease. Good or moderate response is defined as follows: Good response: DAS28 at the time point ≤ 3.2 and improvement from baseline > 1.2 Moderate response: DAS28 at the time point > 3.2 and improvement from baseline > 1.2, or DAS28 at the time point ≤ 5.1 and improvement from baseline > 0.6 and ≤ 1.2 (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 25.0 |
| Apremilast 20 mg | 41.1 |
| Apremilast 30 mg | 44.3 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 48.7 |
| Apremilast 20 mg | 54.7 |
| Apremilast 30 mg | 66.7 |
Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 70.7 |
| Placebo / Apremilast 30 mg | 81.0 |
| Apremilast 20 mg | 65.9 |
| Apremilast 30 mg | 69.4 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 93.8 |
| Placebo / Apremilast 30 mg | 94.7 |
| Apremilast 20 mg | 87.1 |
| Apremilast 30 mg | 85.9 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 20. Two-sided 95% confidence interval is based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 75.0 |
| Placebo / Apremilast 30 mg | 78.9 |
| Apremilast 20 mg | 68.6 |
| Apremilast 30 mg | 68.8 |
Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 33.3 |
| Apremilast 20 mg | 42.7 |
| Apremilast 30mg | 40.5 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 19.1 |
| Apremilast 20 mg | 21.4 |
| Apremilast 30 mg | 36.9 |
Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Achilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval was based on the Clopper-Pearson method. (NCT01307423)
Timeframe: Baseline and Week 52
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo / Apremilast 20 mg | 39.0 |
| Placebo / Apremilast 30 mg | 61.9 |
| Apremilast 20 mg | 39.6 |
| Apremilast 30 mg | 45.9 |
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain. (NCT01307423)
Timeframe: Week 0 to Week 260; median duration of exposure to apremilast 20 mg BID was 168.93 weeks and 229.36 weeks for apremilast 30 mg BID
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE (SAE) | Drug-Related (SAE) | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Wirhdrawal | Any TEAE Leading to Death | |
| Apremilast 20 mg (Pre-Switch) | 188 | 89 | 24 | 35 | 6 | 41 | 22 | 0 |
| Apremilast 20/30 mg (Post-Switch) | 60 | 16 | 3 | 5 | 1 | 5 | 2 | 0 |
| Apremilast 30 mg | 204 | 113 | 23 | 36 | 6 | 36 | 26 | 0 |
A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE is any AE that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or constitutes an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale: Mild: asymptomatic or with mild symptoms, Moderate: symptoms causing moderate discomfort or Severe: symptoms causing severe discomfort or pain. (NCT01307423)
Timeframe: Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-Related TEAE | Any Severe TEAE | Any Serious TEAE (SAE) | Drug-Related (SAE) | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 20mg | 87 | 40 | 4 | 3 | 0 | 11 | 4 | 0 |
| Apremilast 30mg | 99 | 58 | 2 | 1 | 1 | 9 | 6 | 0 |
| Placebo | 73 | 25 | 6 | 5 | 0 | 8 | 4 | 0 |
Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0=lowest disease activity and 100=highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0=lowest disease activity and 100=highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 24.4 |
| Apremilast 20 mg | 38.9 |
| Apremilast 30 mg | 45.5 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. (NCT01307423)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.01 |
| Apremilast 20 mg | 2.39 |
| Apremilast 30 mg | 3.19 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). SF-36 domain scores were first calculated to range from 0 to100 and then transformed to norm-based scores (the norm-based scores in the US general population have an average of 50 and a standard deviation of 10). Norm-based scores were used in analyses, with higher scores indicating a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. (NCT01307423)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 0.16 |
| Apremilast 20 mg | 2.13 |
| Apremilast 30 mg | 3.88 |
The investigator global assessment scale is a gestalt global assessment made by an investigator describing the overall disease severity of the patient. It is a categorical scale that includes 0-clear, 1-almost clear, 2-mild,3- moderate, 4-severe, and 5-very severe. The reduction in IGA score from baseline to month three (end of study) in the 20mg arm and month six (end of study) in the 30mg arm was evaluated for efficacy. (NCT01393158)
Timeframe: Mean change in IGA score measured at Baseline and Month 3, (if on 20mg arm) or Baseline and Month 6 (if on 30mg arm)
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| Mild | Moderate | Severe | Very Severe | |
| Apremilast 20 BID | 0 | 2 | 3 | 1 |
| Apremilast 30 BID | 1 | 8 | 1 | 0 |
The pruritus visual analog scale (VAS) is a 10 cm (100 mm) visual analog scale that measures up patient's itch severity with 10 (100 mm) representing the worst imaginable and 0 representing no itch. This is a validated scale with a change of three from baseline to month three in the 20mg arm (end of study) and month six in the 30mg arm (end of study) being clinically relevant. (NCT01393158)
Timeframe: Mean change in Pruritus (Visual Analog Scale) score measured at Baseline and Month 3, (if on 20mg arm) or Baseline and Month 6 (if on 30mg arm)
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20mg BID | -32.2 |
| Apremilast 30mg BID | -13.4 |
The eczema area and severity index (EASI) is a composite score measuring physical signs of atopic dermatitis. The scale ranges from 0-72. The components measuring severity are four signs/symptoms of atopic dermatitis: erythema, population, excoriation and lichenification on a scale of 0-3 for each body of the four body regions (head/neck, trunk, arms, legs). The component measuring area is a body surface area measurement of each region. The area and severity of each body region is weighted based on size of region which are added together for the complete score. The score for each patient's with scores between 0 and 7 are considered mild ,between 7 and 21 are considered moderate, and greater than 21 are considered severe. In this study the change in EASI score between baseline and month three (end of study) in the 20 mg arm and month six in the 30 mg arm, baseline EASI score was subtracted from month 3 or month 6 score in the 30mg arm,and calculated as a final outcome data point. (NCT01393158)
Timeframe: Mean change in EASI score measured at Baseline and Month 3, (if on 20mg arm) or Baseline and Month 6 (if on 30mg arm)
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20 BID | -8.8 |
| Apremilast 30mg BID | -8.2 |
"The dermatology life quality index (DLQI) is a validated quality-of-life scale that measures the impact of skin disease. It is a 10 question instrument. Scores of 0 over 0-1 means there is no effect on the patient's life. Scores between 2 and 5 represent a small effect on patient's life. Scores between 6 and 10 correspond to a moderate effect on patient's life. Scores between 11 and 20 correspond to a very large effect on the patient's life. And scores between 21 and 30 correspond to an extremely large effect on patient's life. The range of the scale between 0 and 30 for the added total of the patient's responses. Each question can be answered on a scale of 0-not at all, 1-a little, 2- a lot, 3- very much with some questions having the option of not relevant. The difference in DLQI score from baseline to month three (end of study) in the 20mg arm and month six (end of study) in the 30mg arm was evaluated for efficacy." (NCT01393158)
Timeframe: Mean change in DLQI scores measured at Baseline and Month 3, (if on 20mg arm) or Baseline and Month 6 (if on 30mg arm)
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast 20 BID | -8.3 |
| Apremilast 30mg BID | -6.3 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | L/h (Geometric Mean) |
|---|---|
| Apremilast Alone | 9.60 |
| Apremilast + IV Rifampin | 10.1 |
| Apremilast + Multiple Dose Oral Rifampin | 34.5 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast Alone | 290 |
| Apremilast + IV Rifampin | 331 |
| Apremilast + Multiple Dose Oral Rifampin | 166 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | liters (Geometric Mean) |
|---|---|
| Apremilast Alone | 112 |
| Apremilast + IV Rifampin | 107 |
| Apremilast + Multiple Dose Oral Rifampin | 305 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Apremilast Alone | 3120 |
| Apremilast + IV Rifampin | 2980 |
| Apremilast + Multiple Dose Oral Rifampin | 869 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Apremilast Alone | 3070 |
| Apremilast + IV Rifampin | 2940 |
| Apremilast + Multiple Dose Oral Rifampin | 850 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | hours (Geometric Mean) |
|---|---|
| Apremilast Alone | 8.12 |
| Apremilast + IV Rifampin | 7.35 |
| Apremilast + Multiple Dose Oral Rifampin | 6.13 |
Plasma concentrations of apremilast were determined by means of a validated, sensitive, and specific high performance liquid chromatography/tandem mass spectrometric (LC-MS/MS) assay. (NCT01561963)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours following apremilast dosing on Days 1, 5, and 20
| Intervention | hours (Median) |
|---|---|
| Apremilast Alone | 2.00 |
| Apremilast + IV Rifampin | 1.50 |
| Apremilast + Multiple Dose Oral Rifampin | 1.00 |
The BASDAI is a composite score based on a participant self-administered survey of six questions measured using a 0 to 10 unit numerical rating scale (NRS) that assessed the participants' five major symptoms of AS: 1) fatigue; 2) spinal pain; 3) peripheral joint pain/swelling; 4) areas of localized tenderness; 5a) morning stiffness severity upon wakening; 5b) morning stiffness duration upon wakening. The participant was asked to mark the box with an X on a 0 to 10 unit NRS for each of the 6 questions. To give each of the five symptoms equal weighting, the mean of the two scores relating to morning stiffness was taken. The resulting 0 to 50 score was divided by 5 to give a final 0 to 10 BASDAI score. A BASDAI score of 4 or greater was considered to be indicative of active AS disease. (NCT01583374)
Timeframe: Baseline and Week 24
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| Placebo | -1.21 |
| Apremilast 20 mg | -1.30 |
| Apremilast 30 mg | -1.18 |
The BASFI is a composite score based on a self-administered survey of 10 questions using a 0 to 10 unit numerical rating scale (NRS) that assesses the degree of mobility and functional ability. The survey consists of 8 questions regarding function in AS and the last 2 reflect the ability to manage everyday life. The patient marks a box with an X on a 0 to 10 unit NRS for 10 questions; the left-hand box of 0 = easy; the right-hand box = impossible. The resulting 0 to 100 score is divided by 10 to give a final 0 to 10 BASFI score. The overall score is the mean of the 10 items and ranges from 0 to 10. A higher score correlates to reduced functional ability. (NCT01583374)
Timeframe: Baseline and Week 24
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| Placebo | -0.94 |
| Apremilast 20 mg | -1.11 |
| Apremilast 30 mg | -0.99 |
A TEAE was an adverse event (AE) with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. A serious AE = results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; or constitutes an important medical event. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = symptoms causing severe pain discomfort. (NCT01583374)
Timeframe: From Week 0 to Week 24; the median duration of exposure was 23.57 weeks for the placebo arm, 23.71 weeks for the apremilast 20 mg arm and 24.00 weeks for the apremilast 30 mg arm.
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any Treatment Emergent Adverse Event | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 20 mg | 91 | 44 | 2 | 3 | 0 | 13 | 11 | 0 |
| Apremilast 30 mg | 88 | 51 | 5 | 6 | 3 | 14 | 13 | 0 |
| Placebo | 83 | 24 | 0 | 1 | 0 | 14 | 7 | 0 |
"The Modified Stoke Ankylosing Spondylitis Spine Score is a scoring method used to determine the amount or degree of ankylosing spondylitis disease that is in the spine based on x-ray radiographs of the spine. The m-SASSS scores 0-3.~0 = No abnormality, 1 = Erosion, Sclerosis or Squaring, 2 = Syndesmophyte, 3 = Total bony Bridging at each Site. An increase in the m-SASSS indicated a worsening of AS disease." (NCT01583374)
Timeframe: Baseline to Week 104 and 260
| Intervention | Units on a Scale (Mean) | |
|---|---|---|
| Week 104 | Week 260 | |
| Apremilast 20 mg | 0.99 | 3.14 |
| Apremilast 20 mg/ Apremilast 30 mg | 0.82 | 2.21 |
| Apremilast 20 mg/Apremilast 20 mg | 1.12 | 3.83 |
| Apremilast 30 mg | 0.65 | 1.79 |
| Placebo/Apremilast 30 mg | 0.98 | 1.92 |
"ASAS 20 was defined as achieving an improvement from baseline of ≥ 20% and ≥ 1 unit in at least 3 of 4 ASAS domains on a scale of 0 to 10 units and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining ASAS domain on a scale of 0 to 10 units. The 4 ASAS domains are:~Patient Global Assessment of Disease (0 - 10 unit Numerical Rating Scale [NRS]); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = not active and the right-hand box = very active~Total Back Pain (0 to 10 unit NRS); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = no pain and the right-hand box = most severe pain~Function (Bath AS Functional Index [BASFI] NRS 0 - 10 unit); participant provides a self-administered survey of 10 questions assessing for degree of mobility and functional ability~Inflammation domain is determined by the mean of 2 Bath AS Disease Activity Index NRS Questions #5 and #6 for morning stiffness) (0 - 10 unit)" (NCT01583374)
Timeframe: Baseline and Week 24
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 31.7 |
| Apremilast 20 mg | 36.2 |
| Apremilast 30 mg | 33.7 |
"ASAS 20 was defined as achieving an improvement from baseline of ≥ 20% and ≥ 1 unit in at least 3 of 4 ASAS domains on a scale of 0 to 10 units and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining ASAS domain on a scale of 0 to 10 units. The 4 ASAS domains are:~Patient Global Assessment of Disease (0 - 10 unit Numerical Rating Scale [NRS]); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = not active and the right-hand box = very active~Total Back Pain (0 to 10 unit NRS); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = no pain and the right-hand box = most severe pain~Function (Bath AS Functional Index [BASFI] NRS 0 - 10 unit); participant provides a self-administered survey of 10 questions assessing for degree of mobility and functional ability~Inflammation domain is determined by the mean of 2 Bath AS Disease Activity Index NRS Questions #5 and #6 for morning stiffness) (0 - 10 unit)" (NCT01583374)
Timeframe: Baseline and Week 16
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 36.6 |
| Apremilast 20 mg | 35.0 |
| Apremilast 30 mg | 32.5 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores (based on US general population with mean of 50 and standard deviation of 10) were used in analyses. Higher scores indicate a higher level of functioning. The PCS encompasses physical functioning, role-physical, and bodily pain, as well as general health and vitality. A positive change from baseline score indicates an improvement (NCT01583374)
Timeframe: Baseline and Week 24
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| Placebo | 3.50 |
| Apremilast 20 mg | 3.46 |
| Apremilast 30 mg | 3.79 |
The ASQoL is a validated disease specific patient reported outcomes instrument to assess the impact of ankylosing spondylitis on the quality of life of individuals with emphasis on the ability of the person to fulfill his or her needs. It consisted of 18 items requesting a yes (score=1) or no (score=0) response to questions related to the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. The summary score ranges 0-18 with higher scores indicating worse quality of life. (NCT01583374)
Timeframe: Baseline and Week 24
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| Placebo | -1.77 |
| Apremilast 20 mg | -1.50 |
| Apremilast 30 mg | -1.52 |
The BASMI-Linear was designed to assess axial status (ie, cervical, dorsal and lumbar spine, hips, and pelvic soft tissue) and to define clinically significant changes in spinal movement. Five dimensions of movement (lateral lumbar flexion, tragus to wall, forward lumbar flexion, maximal intermalleolar distance, and cervical rotation) were measured and normalized on 0 to 10 unit NRS. The average of these scores was the total BASMI score, ranging from 0-10 with higher values indicating more severe limitation in spinal mobility. (NCT01583374)
Timeframe: Baseline and Week 24
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| Placebo | -0.19 |
| Apremilast 20 mg | -0.16 |
| Apremilast 30 mg | -0.13 |
A TEAE was an adverse event (AE) with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. A serious AE = results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; or constitutes an important medical event. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = symptoms causing severe pain discomfort. (NCT01583374)
Timeframe: Week 0 to week 260; overall mean duration of exposure to apremilast 20 mg and 30 mg BID was 160.96 weeks
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any Treatment Emergent Adverse Event | Any Severe TEAE | Any Serious TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 20 mg | 114 | 5 | 12 | 22 | 18 | 0 |
| Apremilast 20/30 mg | 47 | 8 | 8 | 11 | 4 | 1 |
| Apremilast 30 mg | 239 | 23 | 41 | 51 | 34 | 1 |
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Apremilast - Fasted | 339.86 |
| Apremilast - Fed | 333.85 |
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | hours (Median) |
|---|---|
| Apremilast - Fasted | 2.50 |
| Apremilast - Fed | 3.00 |
An adverse event (AE) was any noxious, unintended, or untoward medical occurrence that appeared or worsened in a participant during the course of this study. It could have been a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. (NCT01634178)
Timeframe: From first dose of study drug in Period 1 up to 5 to 10 days after dosing in Period 2, approximately 20 days.
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Any adverse event | Adverse events related to study drug | Serious adverse events | Discontinued due to adverse event | Discontinued due to adverse event related to study drug | |
| Apremilast - Fasted | 9 | 4 | 0 | 0 | 0 |
| Apremilast - Fed | 5 | 3 | 0 | 2 | 1 |
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | mL (Geometric Mean) |
|---|---|
| Apremilast - Fasted | 121735.96 |
| Apremilast - Fed | 98582.15 |
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | mL/hr (Geometric Mean) |
|---|---|
| Apremilast - Fasted | 9499.80 |
| Apremilast - Fed | 8556.28 |
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Apremilast - Fasted | 3157.96 |
| Apremilast - Fed | 3506.19 |
"Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay.~AUC0-t was calculated using the linear trapezoidal method (linear up log down) when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing." (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Apremilast - Fasted | 3083.05 |
| Apremilast - Fed | 3436.39 |
Plasma concentrations of apremilast were determined by using a validated liquid chromatography-tandem mass spectrometry assay. (NCT01634178)
Timeframe: Day 1 of each treatment period at pre-dose, and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | hours (Geometric Mean) |
|---|---|
| Apremilast - Fasted | 8.88 |
| Apremilast - Fed | 7.99 |
(NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | liters (Geometric Mean) |
|---|---|
| Males (Combined) | 128 |
| Females (Combined) | 123 |
The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | h*ng/mL (Geometric Mean) |
|---|---|
| Young: Apremilast | 2900 |
| Elderly: Apremilast | 3323 |
"The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.~AUC0-t was calculated using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing." (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | h*ng/mL (Geometric Mean) |
|---|---|
| Young: Apremilast | 2832 |
| Elderly: Apremilast | 3235 |
The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | h*ng/mL (Geometric Mean) |
|---|---|
| Males (Combined) | 2673 |
| Females (Combined) | 3499 |
(NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | hours (Mean) |
|---|---|
| Males (Combined) | 8.06 |
| Females (Combined) | 10.3 |
The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Young: Apremilast | 302 |
| Elderly: Apremilast | 321 |
The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Males (Combined) | 299 |
| Females (Combined) | 322 |
(NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | hours (Mean) |
|---|---|
| Young: Apremilast | 9.41 |
| Elderly: Apremilast | 9.15 |
The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | hours (Median) |
|---|---|
| Males (Combined) | 2.5 |
| Females (Combined) | 2.75 |
"The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL.~AUC0-t was calculated using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing." (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | h*ng/mL (Geometric Mean) |
|---|---|
| Males (Combined) | 2634 |
| Females (Combined) | 3382 |
An adverse event (AE) was any noxious, unintended, or untoward medical occurrence that appeared or worsened in a participant during the course of the study. It could have been a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a pre-existing condition) was considered an AE. (NCT01634191)
Timeframe: From first dose of study drug up to 11 days
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any adverse event | Adverse event related to study drug | Serious adverse events | Serious adverse events related to study drug | Discontinued due to adverse event | Discontinued due to adverse event related to study drug | |
| Elderly Females | 5 | 1 | 0 | 0 | 0 | 0 |
| Elderly Males | 2 | 0 | 0 | 0 | 0 | 0 |
| Young Females | 1 | 1 | 0 | 0 | 0 | 0 |
| Young Males | 2 | 2 | 0 | 0 | 0 | 0 |
(NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | L/hr (Geometric Mean) |
|---|---|
| Young: Apremilast | 10.4 |
| Elderly: Apremilast | 9.03 |
(NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | L/hr (Geometric Mean) |
|---|---|
| Males (Combined) | 11.2 |
| Females (Combined) | 8.57 |
The lower limit of quantitation for apremilast plasma concentrations was 1.0 ng/mL. (NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | hours (Median) |
|---|---|
| Young: Apremilast | 2.50 |
| Elderly: Apremilast | 2.50 |
(NCT01634191)
Timeframe: Day 1 predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12, 24, 36, and 48 hours after dosing.
| Intervention | liters (Geometric Mean) |
|---|---|
| Young: Apremilast | 136 |
| Elderly: Apremilast | 115 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing. (NCT01690299)
Timeframe: Baseline to Week 16
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 11.9 |
| Apremilast Plus Placebo Injection | 39.8 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing. (NCT01690299)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 11.9 |
| Etanercept 50mg Plus Placebo Tablet | 48.2 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The PASI score was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing. (NCT01690299)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 33.3 |
| Apremilast Plus Placebo Injection | 62.7 |
| Etanercept Plus Placebo Tablet | 83.1 |
"BSA is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline was determined at each visit of the study, and is calculated as 100*(post-baseline BSA - baseline BSA) / baseline BSA." (NCT01690299)
Timeframe: Baseline to Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -16.3 |
| Apremilast Plus Placebo Injection | -47.7 |
| Etanercept Plus Placebo Tablets | -56.1 |
The SF-36 is a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Scores from the 8 scales were transformed to the norm-based scores using weights from U.S. general population to have a mean of 50 and variance = 10, with higher scores indicating better health. From these 8 scale, two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS), both having the same mean of 50 and variance = 10 as noted for the individual scales for the U.S. general population, and with higher scores indicating better health. For MCS, change from baseline was calculated, where change = visit value - baseline value. (NCT01690299)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 2.6 |
| Apremilast Plus Placebo Injection | 3.5 |
| Etanercept Plus Placebo Tablets | 4.8 |
Psoriasis flare is an AE and represents an atypical or unusual worsening of disease during treatment. It is defined as a sudden intensification of psoriasis requiring medical intervention or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is an AE and is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. This exacerbation is characterized by a PASI ≥125% of baseline or a new generalized pustular, erythrodermic, or more inflammatory psoriasis after stopping therapy. PASI ≥125% of baseline score at any visit after the last dose date for those who discontinued within the phase. (NCT01690299)
Timeframe: From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo or etanercept who were switched at Week 16) until 28 days after the last dose of apremilast.
| Intervention | participants (Number) | ||
|---|---|---|---|
| Any psoriasis flare captured as a TEAE | Any psoriasis rebound captured as a TEAE | Those with PASI ≥125% baseline score and D/C APR | |
| Apremilast/Apremilast | 4 | 2 | 0 |
| Etanercept/Apremilast | 0 | 7 | 1 |
| Placebo/Apremilast | 1 | 1 | 0 |
"DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best." (NCT01690299)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -3.9 |
| Apremilast 30mg Plus Placebo Injection | -8.4 |
| Etanercept 50mg Plus Placebo Tablet | -7.8 |
A TEAE is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug for participants who discontinued early. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the patient's health, including laboratory test values, regardless of etiology. Any worsening (ie, clinically significant adverse change in frequency or intensity of a preexisting condition) should be considered an AE. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes above. (NCT01690299)
Timeframe: Week 0 to Week 16; mean duration of exposure was 14.90 weeks for placebo group, 15.13 weeks for apremilast group and 15.87 weeks for Etanercept group
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast Plus Placebo Injection | 59 | 27 | 3 | 3 | 2 | 9 | 3 | 0 |
| Etanercept Plus Placebo Tablets | 44 | 21 | 3 | 2 | 1 | 3 | 2 | 0 |
| Placebo | 45 | 17 | 2 | 0 | 0 | 1 | 2 | 0 |
A TEAE in the apremilast-exposure phase is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes listed above. (NCT01690299)
Timeframe: From the first dose of apremilast (either Week 0 for participants originally randomized to apremilast or Week 16 for those originally randomized to placebo or etanercept who were switched to apremilast at week 16) until 28 days after last apremilast dose
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast/Apremilast | 71 | 36 | 7 | 6 | 2 | 13 | 7 | 0 |
| Etanercept/Apremilast | 54 | 15 | 7 | 4 | 1 | 7 | 2 | 0 |
| Placebo/Apremilast | 45 | 23 | 4 | 5 | 2 | 8 | 3 | 0 |
The sPGA is an assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator should factor in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign is averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score. (NCT01690299)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 3.6 |
| Apremilast Plus Placebo Injection | 21.7 |
| Etanercept Plus Placebo Tablet | 28.9 |
Psoriasis flare is an AE and represents an atypical or unusual worsening of disease during treatment. It is defined as a sudden intensification of psoriasis requiring medical intervention or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is an AE and is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. This exacerbation is characterized by a PASI ≥125% of baseline or a new generalized pustular, erythrodermic, or more inflammatory psoriasis after stopping therapy. (NCT01690299)
Timeframe: Week 0 to Week 16; Placebo controlled phase
| Intervention | participants (Number) | ||
|---|---|---|---|
| Any psoriasis flare captured as a TEAE | Any psoriasis rebound captured as a TEAE | Those with PASI ≥125% baseline score and D/C APR | |
| Apremilast Plus Placebo Injection | 1 | 0 | 0 |
| Etanercept Plus Placebo Tablets | 0 | 0 | 0 |
| Placebo | 3 | 0 | 1 |
The Lattice System Physician's Global Assessment is a global assessment performed by the investigator of psoriasis severity. Integrating ranges of BSA involvement with assessments of overall plaque severity (using a 4 point scale from none to marked for the signs of plaque elevation, erythema and scale), the LS-PGA produces an overall assessment of psoriasis severity on an 8-point scale, ranging from clear to very severe. To determine the final score, the lattice portion is governed by the BSA and among the plaque qualities, weights plaque elevation as most important, erythema next, and scale least. (NCT01690299)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 6.0 |
| Apremilast Plus Placebo Injection | 24.1 |
| Etanercept Plus Placebo Tablets | 22.9 |
"Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 20% improvement in 78 tender joint count;~≥ 20% improvement in 76 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters:~Patient's self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);~Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);~Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);~Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);~C-Reactive Protein (CRP)" (NCT01925768)
Timeframe: Baseline and Weeks 52 and 104
| Intervention | percentage of partcipants (Number) | |
|---|---|---|
| Week 52 | Week 104 | |
| Apremilast (APR) | 67.1 | 59.4 |
| Placebo/Apremilast (PBO-APR) | 60.0 | 66.2 |
"Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 20% improvement in 78 tender joint count;~≥ 20% improvement in 76 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters:~Patient's self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);~Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);~Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);~Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);~C-Reactive Protein (CRP)" (NCT01925768)
Timeframe: Baseline and at Weeks 2, 4, 6, 8, 12 and 20
| Intervention | percentage of participants (Number) | |||||
|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 12 | Week 20 | |
| Apremilast (APR) 30 mg | 16.4 | 24.5 | 37.3 | 36.4 | 40.0 | 43.6 |
| Placebo (PBO) | 6.4 | 15.6 | 19.3 | 22.9 | 28.4 | 24.8 |
A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT01925768)
Timeframe: Start of lst dose of IP up to week 104: Weeks 0 to104 for those initially randomized to APR 30 mg BID, Weeks 16 -104 for PBO-treated patients who EE to APR at Week 16 and from Weeks 24-104 for PBO-treated patients who transitioned to APR at Week 24
| Intervention | Participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any drug-related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug-related TEAE | Any TEAE leading to study dose interruption | Any TEAE leading to study drug withdrawal | Any TEAE leading to death | |
| Apremilast (APR) 30 mg | 157 | 52 | 8 | 15 | 0 | 28 | 17 | 1 |
The SF-36 (v 2.0) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01925768)
Timeframe: Baseline and Weeks 52 and 104
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Week 52 | Week 104 | |
| Apremilast (APR) | 6.00 | 5.95 |
| Placebo/Apremilast (PBO-APR) | 5.11 | 5.78 |
Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement. (NCT01925768)
Timeframe: Baseline and Weeks 52 and 104
| Intervention | minutes (Mean) | |
|---|---|---|
| Week 52 | Week 104 | |
| Apremilast (APR) | -5.7 | -7.0 |
| Placebo/Apremilast (PBO-APR) | 3.3 | -11.9 |
"The DAS28 measures the severity of disease at a specific time and is derived from the following variables:~28 tender joint count~28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;~C-reactive protein (CRP)~Patient's global assessment of disease activity. DAS28 (CRP) scores range from 0 to 9.4. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. A negative change from baseline indicates improvement." (NCT01925768)
Timeframe: Baseline and Weeks 52 and 104
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Week 52 | Week 104 | |
| Apremilast (APR) | -1.71 | -1.70 |
| Placebo/Apremilast (PBO-APR) | -1.46 | -1.62 |
HAQ-DI is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement. (NCT01925768)
Timeframe: Baseline and Weeks 52 and 104
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Week 52 | Week 104 | |
| Apremilast (APR) | -0.395 | -0.357 |
| Placebo/Apremilast (PBO-APR) | -0.323 | -0.382 |
Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. The response of no improvement includes subjects who had no change or worsened. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment. (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo (PBO) | 20.2 |
| Apremilast (APR) | 40.0 |
Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment. Full Analysis Set; Participants who discontinued early prior to Week 16 and those who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders. (NCT01925768)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo (PBO) | 25.7 |
| Apremilast (APR) 30 mg | 46.4 |
"Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 20% improvement in 78 tender joint count;~≥ 20% improvement in 76 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters:~Patient's self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);~Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);~Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);~Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);~C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders." (NCT01925768)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo (PBO) | 20.2 |
| Apremilast (APR) 30 mg | 38.2 |
"Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met:~≥ 20% improvement in 78 tender joint count;~≥ 20% improvement in 76 swollen joint count; and~≥ 20% improvement in at least 3 of the 5 following parameters:~Patient's self-assessment of pain (measured on a 0 to 10 unit numeric rating scale [NRS]);~Patient's global self-assessment of disease activity (measured on a 0 to 10 unit NRS);~Physician's global assessment of disease activity (measured on a 0 to 10 unit NRS);~Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);~C-Reactive Protein (CRP) Those who withdrew early or who did not have sufficient data at Week 16 were counted as non-responders." (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo (PBO) | 24.8 |
| Apremilast (APR) 30 mg | 43.6 |
Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement. (NCT01925768)
Timeframe: Baseline and Week 16
| Intervention | minutes (Mean) |
|---|---|
| Placebo (PBO) | 21.7 |
| Apremilast (APR) 30 mg | -7.2 |
A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT01925768)
Timeframe: Date of first dose of study drug to Week 24; median duration of exposure during placebo controlled phase was 24.14 weeks
| Intervention | Participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any drug-related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug-related TEAE | Any TEAE leading to study drug withdrawal | Any TEAE leading to study dose interruption | Any TEAE leading to death | |
| Apremilast (APR) 30 mg | 73 | 30 | 2 | 3 | 0 | 10 | 10 | 0 |
| Placebo (PBO) | 69 | 18 | 4 | 5 | 0 | 5 | 7 | 0 |
Morning stiffness was the participant's assessment of how long their morning stiffness lasted after first waking up in the morning, on average, during the previous week. A higher value indicates longer duration, and a negative change from baseline indicates improvement. (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | minutes (Mean) |
|---|---|
| Placebo (PBO) | 21.9 |
| Apremilast (APR) 30 mg | -5.7 |
"The DAS28 measures the severity of disease at a specific time and is derived from the following variables:~28 tender joint count~28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;~C-reactive protein (CRP)~Patient's global assessment of disease activity. DAS28 (CRP) scores range from 0 to 9.4. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. A negative change from baseline indicates improvement." (NCT01925768)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | -0.39 |
| Apremilast (APR) 30 mg | -1.07 |
The SF-36 (v 2.0) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary (PCS) score includes the physical functioning, role physical, bodily pain, and general health domains. Minimum clinically important difference (MCID) for the scale scores, as well as the PCS and MCS, is defined as a 2.5-point improvement (increase) from baseline. The summary scores range from 0 to 100, with lower scores reflecting more disability, and higher scores reflecting less disability and better health. The 8 domains are regrouped into the PCS and MCS scores. (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | 1.60 |
| Apremilast (APR) 30 mg | 5.00 |
"The DAS28 measures the severity of disease at a specific time and is derived from the following variables:~28 tender joint count~28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee;~C-reactive protein (CRP)~Patient's global assessment of disease activity. DAS28 (CRP) scores range from 0 to 9.4. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. A higher value indicates higher disease activity, and a negative change from baseline indicates improvement." (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | -0.76 |
| Apremilast (APR) 30 mg | -1.26 |
HAQ-DI is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement. (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | -0.169 |
| Apremilast (APR) 30 mg | -0.273 |
HAQ-DI is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A higher score indicates worse physical functioning, and a negative change from baseline indicates improvement. (NCT01925768)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | -0.055 |
| Apremilast (APR) 30 mg | -0.205 |
The SF-36 (v 2.0) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. (NCT01925768)
Timeframe: Baseline and Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | -1.04 |
| Apremilast (APR) 30 mg | 2.43 |
Morning stiffness severity was the participant's assessment of how severe their morning stiffness was after first waking up in the morning, on average, during the previous week. The severity was recorded as none, mild, moderate, moderately severe, or very severe. Improvement is defined as the change from baseline of a more severe assessment to less severe assessment. (NCT01925768)
Timeframe: Baseline and Weeks 52 and 104
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 52 | Week 104 | |
| Apremilast (APR) | 57.5 | 59.4 |
| Placebo/Apremilast (PBO-APR) | 57.1 | 50.7 |
The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from baseline score indicates an improvement. (NCT01925768)
Timeframe: Baseline and Week 24
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo (PBO) | 1.26 |
| Apremilast (APR) 30 mg | 3.94 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. The PASI scores range from 0 to 72, with higher scores reflecting a greater disease severity. (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -3.7 |
| Apremilast 20mg | -33.1 |
| Apremilast 30mg | -43.1 |
PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing. (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 21.4 |
| Apremilast 20mg | 41.2 |
| Apremilast 30mg | 50.6 |
PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing. (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 7.1 |
| Apremilast 20mg | 23.5 |
| Apremilast 30mg | 28.2 |
The sPGA is a measure of psoriasis disease severity at the time of evaluation by the Investigator. It does not compare assessments across visits or rely on investigator recall or prior disease. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examines all of the lesions on the participant and assigns a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equals the overall sPGA score. (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 8.8 |
| Apremilast 20mg | 23.9 |
| Apremilast 30mg | 29.6 |
An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| ≥ At least 1 TEAE | ≥ 1 Drug-related TEAE | ≥ At least 1 Severe TEAE | ≥ 1 Serious TEAE | Any Serious Drug-related TEAE | ≥ 1 TEAE leading to Drug Interruption | ≥ 1 TEAE Leading to Drug Withdrawal | ≥ 1 TEAE Leading to Death | |
| Apremilast 20mg | 49 | 18 | 4 | 4 | 2 | 2 | 10 | 0 |
| Apremilast 30mg | 44 | 25 | 0 | 0 | 0 | 0 | 6 | 0 |
| Placebo | 35 | 8 | 1 | 0 | 0 | 2 | 4 | 0 |
An AE was any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose. (NCT01988103)
Timeframe: From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo who were re-randomized at Week 16) until 28 days after the last dose of apremilast.
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| ≥ At Least 1 TEAE | ≥ 1 Drug-related TEAR | ≥ At Least 1 Severe TEAE | ≥ 1 Serious TEAE | Any Serious Drug-related TEAE | ≥ 1 TEAE leading to Drug Interruption | ≥ 1 TEAE Leading to Drug Withdrawal | ≥ 1 TEAE Leading to Death | |
| Apremilast 20mg | 94 | 34 | 12 | 11 | 5 | 6 | 19 | 1 |
| Apremilast 30mg | 89 | 37 | 2 | 2 | 0 | 2 | 10 | 0 |
SF-36 is a 36-item general health status instrument often used in clinical trials and health services research. It consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better quality of life (better functioning) (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -1.59 |
| Apremilast 20mg | -0.71 |
| Apremilast 30mg | 0.27 |
The pruritus visual analog scale (VAS) was used to measure the amount of itching and discomfort a participant experiences. Participant's assessment of pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? Higher scores correspond to more severe symptom or disease. The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no itch at all and the right-hand boundary represents the worst itch imaginable. The distance from the vertical line to the left-hand boundary is recorded. VAS scores range from 0 to 100 mm, where higher scores correspond to worse pruritis (itch). (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 7.1 |
| Apremilast 20mg | -7.5 |
| Apremilast 30mg | -17.7 |
"Dermatology Life Quality Index (DLQI) was developed as a practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains 10 items dealing with the participants skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score has a possible range from 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best." (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Least Squares Mean) |
|---|---|
| Placebo | 1.3 |
| Apremilast 20mg | -0.5 |
| Apremilast 30mg | -2.2 |
"BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the subject's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area." (NCT01988103)
Timeframe: Baseline to Week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 7.5 |
| Apremilast 20mg | -21.6 |
| Apremilast 30mg | -30.5 |
A TEAE is an adverse event with a start date on or after the date of the first dose of investigational product (IP) and no later than 28 days after the last dose of IP. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. (NCT02087943)
Timeframe: Baseline to Week 24; median duration of apremilast 30 mg was 23.3 weeks and 22.4 weeks for apremilast 40 mg
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| TEAE | Drug-related TEAE | Severe TEAE | Serious TEAE (SAE) | Drug-related SAE | TEAE Leading to Drug Interruption | TEAE Leading to Drug Withdrawal | Death | |
| Apremilast 30 mg | 49 | 29 | 1 | 2 | 0 | 0 | 3 | 0 |
| Apremilast 40 mg | 61 | 38 | 1 | 3 | 2 | 8 | 9 | 0 |
EASI is a validated composite scoring system integrating the proportion of the body region (area) involved and the intensity of key signs of atopic dermatitis (AD). A representative lesion is selected for each of the four body regions for assessing the intensity of each of the four signs (erythema, induration /papulation, excoriation, and lichenification). Symptoms (eg, pruritus) and secondary signs (eg, xerosis, scaling) are excluded from the assessment. The total EASI score ranges from 0 to 72. A higher score indicated worse disease status, and a negative change from baseline indicated improvement. (NCT02087943)
Timeframe: Baseline to Week 12
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -10.98 |
| Apremilast 30 mg | -25.99 |
| Apremilast 40 mg | -31.57 |
"The sPGA-A is intended to assess the global severities (ie, a visual average integrating all areas of AD) of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded) based on a 5-point scale of cleared (0), almost cleared (1), mild (2), moderate (3) and severe (4)." (NCT02087943)
Timeframe: Baseline to Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 6.3 |
| Apremilast 30 mg | 3.4 |
| Apremilast 40 mg | 14.3 |
A TEAE is an adverse event with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre existing condition) should be considered an AE. A serious AE is any which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. (NCT02087943)
Timeframe: Baseline to Week 12
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| TEAE | Drug-related TEAE | Severe TEAE | Serious TEAE (SAE) | Drug-related SAE | TEAE Leading to Drug Interruption | TEAE Leading to Drug Withdrawal | Death | |
| Apremilast 30 mg | 36 | 26 | 0 | 1 | 0 | 0 | 2 | 0 |
| Apremilast 40 mg | 44 | 27 | 1 | 2 | 1 | 4 | 6 | 0 |
| Placebo | 30 | 8 | 0 | 0 | 0 | 3 | 1 | 0 |
The EASI 50 reduction (defined as ≥ 50% reduction from baseline in EASI score) was selected to serve as the key responder endpoint. A ≥ 50% improvement is clinically meaningful for this population. (NCT02087943)
Timeframe: Baseline to Week 12
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 32.8 |
| Apremilast 30 mg | 31.0 |
| Apremilast 40 mg | 42.9 |
"The participant completed a daily diary recording the average intensity of pruritus they experienced during the preceding 24 hrs. The intensity of pruritus was assessed using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable). It should be noted that this NRS is distinct from the pruritus, Visual Analogue Scale (VAS) in the Modified SCORAD Index with respect to recall period (three days for the VAS). The weekly NRS score was calculated as the average of the NRS scores over 7 days within the specified week. A higher score indicated worse disease status, and a negative change from baseline indicated improvement." (NCT02087943)
Timeframe: Baseline to Week 4
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | -4.83 |
| Apremilast 30 mg | -10.00 |
| Apremilast 40 mg | -9.00 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Median) |
|---|---|
| Group 3: Apremilast Immediate Release | 3.00 |
| Group 3: Apremilast Modified Release 8 | 4.00 |
| Group 3: Apremilast Modified Release 9 | 4.00 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | L/h (Geometric Mean) |
|---|---|
| Group 4: Apremilast Immediate Release | 8.57 |
| Group 4: Apremilast Modified Release 11 | 13.92 |
| Group 4: Apremilast Modified Release 12 | 13.62 |
| Group 4: Apremilast Modified Release 13 | 16.83 |
| Group 4: Apremilast Modified Release 14 | 14.88 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | liters (Geometric Mean) |
|---|---|
| Group 4: Apremilast Immediate Release | 77.30 |
| Group 4: Apremilast Modified Release 11 | 148.66 |
| Group 4: Apremilast Modified Release 12 | 147.59 |
| Group 4: Apremilast Modified Release 13 | 172.16 |
| Group 4: Apremilast Modified Release 14 | 153.18 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 4: Apremilast Immediate Release | 7000.35 |
| Group 4: Apremilast Modified Release 11 | 5747.12 |
| Group 4: Apremilast Modified Release 12 | 5875.19 |
| Group 4: Apremilast Modified Release 13 | 4753.79 |
| Group 4: Apremilast Modified Release 14 | 5374.83 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 4: Apremilast Immediate Release | 6976.02 |
| Group 4: Apremilast Modified Release 11 | 5701.21 |
| Group 4: Apremilast Modified Release 12 | 5811.24 |
| Group 4: Apremilast Modified Release 13 | 4700.70 |
| Group 4: Apremilast Modified Release 14 | 5324.80 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Geometric Mean) |
|---|---|
| Group 4: Apremilast Immediate Release | 6.25 |
| Group 4: Apremilast Modified Release 11 | 7.40 |
| Group 4: Apremilast Modified Release 12 | 7.51 |
| Group 4: Apremilast Modified Release 13 | 7.09 |
| Group 4: Apremilast Modified Release 14 | 7.13 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Group 4: Apremilast Immediate Release | 438.90 |
| Group 4: Apremilast Modified Release 11 | 480.59 |
| Group 4: Apremilast Modified Release 12 | 481.10 |
| Group 4: Apremilast Modified Release 13 | 316.43 |
| Group 4: Apremilast Modified Release 14 | 450.23 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 4: Apremilast Modified Release 11 | 82.10 |
| Group 4: Apremilast Modified Release 12 | 83.31 |
| Group 4: Apremilast Modified Release 13 | 68.71 |
| Group 4: Apremilast Modified Release 14 | 77.68 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 4: Apremilast Modified Release 11 | 46.18 |
| Group 4: Apremilast Modified Release 12 | 46.86 |
| Group 4: Apremilast Modified Release 13 | 38.65 |
| Group 4: Apremilast Modified Release 14 | 43.70 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.~A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event." (NCT02236988)
Timeframe: Adverse events were collected for 7 to 10 days after each treatment.
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAEs related to study drug | Serious adverse events | Serious adverse events related to study drug | Discontinuations due to adverse events | Deaths | |
| Group 1: Apremilast Immediate Release | 5 | 4 | 0 | 0 | 0 | 0 |
| Group 1: Apremilast Modified Release 1 | 4 | 1 | 0 | 0 | 0 | 0 |
| Group 1: Apremilast Modified Release 2 | 2 | 2 | 0 | 0 | 0 | 0 |
| Group 1: Apremilast Modified Release 3 | 1 | 1 | 0 | 0 | 0 | 0 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.~A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event." (NCT02236988)
Timeframe: Adverse events were collected for 7 to 10 days after each treatment.
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAEs related to study drug | Serious adverse events | Serious adverse events related to study drug | Discontinuations due to adverse events | Deaths | |
| Group 2: Apremilast Immediate Release | 4 | 4 | 0 | 0 | 0 | 0 |
| Group 2: Apremilast Modified Release 4 | 4 | 2 | 0 | 0 | 0 | 0 |
| Group 2: Apremilast Modified Release 5 | 6 | 5 | 0 | 0 | 0 | 0 |
| Group 2: Apremilast Modified Release 6 | 5 | 4 | 0 | 0 | 0 | 0 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.~A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event." (NCT02236988)
Timeframe: Adverse events were collected for 7 to 10 days after each treatment.
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAEs related to study drug | Serious adverse events | Serious adverse events related to study drug | Discontinuations due to adverse events | Deaths | |
| Group 3: Apremilast Immediate Release | 5 | 1 | 0 | 0 | 0 | 0 |
| Group 3: Apremilast Modified Release 8 | 3 | 0 | 0 | 0 | 0 | 0 |
| Group 3: Apremilast Modified Release 9 | 3 | 2 | 0 | 0 | 0 | 0 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.~A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event." (NCT02236988)
Timeframe: Adverse events were collected for 7 to 10 days after each treatment.
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE related to study drug | Serious adverse events | Serious adverse events related to study drug | Discontinuation due to adverse events | Deaths | |
| Group 4: Apremilast Immediate Release | 13 | 9 | 0 | 0 | 0 | 0 |
| Group 4: Apremilast Modified Release 11 | 7 | 7 | 0 | 0 | 0 | 0 |
| Group 4: Apremilast Modified Release 12 | 7 | 6 | 0 | 0 | 0 | 0 |
| Group 4: Apremilast Modified Release 13 | 7 | 6 | 0 | 0 | 0 | 0 |
| Group 4: Apremilast Modified Release 14 | 9 | 7 | 0 | 0 | 0 | 0 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 3: Apremilast Modified Release 8 | 81.14 |
| Group 3: Apremilast Modified Release 9 | 79.00 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 1: Apremilast Immediate Release | 6918.49 |
| Group 1: Apremilast Modified Release 1 | 4277.83 |
| Group 1: Apremilast Modified Release 2 | 4925.69 |
| Group 1: Apremilast Modified Release 3 | 5103.07 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Median) |
|---|---|
| Group 4: Apremilast Immediate Release | 3.00 |
| Group 4: Apremilast Modified Release 11 | 4.00 |
| Group 4: Apremilast Modified Release 12 | 4.00 |
| Group 4: Apremilast Modified Release 13 | 4.01 |
| Group 4: Apremilast Modified Release 14 | 3.52 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | L/h (Geometric Mean) |
|---|---|
| Group 1: Apremilast Immediate Release | 8.63 |
| Group 1: Apremilast Modified Release 1 | 17.32 |
| Group 1: Apremilast Modified Release 2 | 15.12 |
| Group 1: Apremilast Modified Release 3 | 14.57 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | liters (Geometric Mean) |
|---|---|
| Group 1: Apremilast Immediate Release | 88.65 |
| Group 1: Apremilast Modified Release 1 | 185.65 |
| Group 1: Apremilast Modified Release 2 | 149.97 |
| Group 1: Apremilast Modified Release 3 | 153.23 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 1: Apremilast Immediate Release | 6955.76 |
| Group 1: Apremilast Modified Release 1 | 4330.66 |
| Group 1: Apremilast Modified Release 2 | 4961.51 |
| Group 1: Apremilast Modified Release 3 | 5147.83 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Geometric Mean) |
|---|---|
| Group 1: Apremilast Immediate Release | 7.12 |
| Group 1: Apremilast Modified Release 1 | 7.43 |
| Group 1: Apremilast Modified Release 2 | 6.88 |
| Group 1: Apremilast Modified Release 3 | 7.29 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Group 1: Apremilast Immediate Release | 409.96 |
| Group 1: Apremilast Modified Release 1 | 267.85 |
| Group 1: Apremilast Modified Release 2 | 329.78 |
| Group 1: Apremilast Modified Release 3 | 345.11 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 1: Apremilast Modified Release 1 | 62.26 |
| Group 1: Apremilast Modified Release 2 | 71.33 |
| Group 1: Apremilast Modified Release 3 | 74.01 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 1: Apremilast Modified Release 1 | 39.85 |
| Group 1: Apremilast Modified Release 2 | 45.65 |
| Group 1: Apremilast Modified Release 3 | 47.37 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Median) |
|---|---|
| Group 1: Apremilast Immediate Release | 3.00 |
| Group 1: Apremilast Modified Release 1 | 4.00 |
| Group 1: Apremilast Modified Release 2 | 4.00 |
| Group 1: Apremilast Modified Release 3 | 4.00 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | L/h (Geometric Mean) |
|---|---|
| Group 2: Apremilast Immediate Release | 9.00 |
| Group 2: Apremilast Modified Release 4 | 13.16 |
| Group 2: Apremilast Modified Release 5 | 15.48 |
| Group 2: Apremilast Modified Release 6 | 14.26 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | liters (Geometric Mean) |
|---|---|
| Group 2: Apremilast Immediate Release | 105.88 |
| Group 2: Apremilast Modified Release 4 | 170.51 |
| Group 2: Apremilast Modified Release 5 | 188.24 |
| Group 2: Apremilast Modified Release 6 | 180.10 |
| Group 3: Apremilast Immediate Release | 101.23 |
| Group 3: Apremilast Modified Release 8 | 169.71 |
| Group 3: Apremilast Modified Release 9 | 186.69 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 2: Apremilast Immediate Release | 6669.26 |
| Group 2: Apremilast Modified Release 4 | 5700.66 |
| Group 2: Apremilast Modified Release 5 | 4843.46 |
| Group 2: Apremilast Modified Release 6 | 5259.40 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 2: Apremilast Immediate Release | 6635.78 |
| Group 2: Apremilast Modified Release 4 | 5634.92 |
| Group 2: Apremilast Modified Release 5 | 4780.60 |
| Group 2: Apremilast Modified Release 6 | 5177.46 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Geometric Mean) |
|---|---|
| Group 2: Apremilast Immediate Release | 8.16 |
| Group 2: Apremilast Modified Release 4 | 8.98 |
| Group 2: Apremilast Modified Release 5 | 8.43 |
| Group 2: Apremilast Modified Release 6 | 8.75 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Group 2: Apremilast Immediate Release | 405.38 |
| Group 2: Apremilast Modified Release 4 | 368.45 |
| Group 2: Apremilast Modified Release 5 | 298.96 |
| Group 2: Apremilast Modified Release 6 | 325.20 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞[test]) / (AUC0-∞[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 2: Apremilast Modified Release 4 | 85.48 |
| Group 2: Apremilast Modified Release 5 | 72.62 |
| Group 2: Apremilast Modified Release 6 | 78.86 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 2: Apremilast Modified Release 4 | 54.71 |
| Group 2: Apremilast Modified Release 5 | 46.48 |
| Group 2: Apremilast Modified Release 6 | 50.47 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Median) |
|---|---|
| Group 2: Apremilast Immediate Release | 2.00 |
| Group 2: Apremilast Modified Release 4 | 4.00 |
| Group 2: Apremilast Modified Release 5 | 3.00 |
| Group 2: Apremilast Modified Release 6 | 4.00 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | L/h (Geometric Mean) |
|---|---|
| Group 3: Apremilast Immediate Release | 10.87 |
| Group 3: Apremilast Modified Release 8 | 17.87 |
| Group 3: Apremilast Modified Release 9 | 18.35 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 3: Apremilast Immediate Release | 5518.28 |
| Group 3: Apremilast Modified Release 8 | 4477.63 |
| Group 3: Apremilast Modified Release 9 | 4359.49 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 3: Apremilast Immediate Release | 5493.38 |
| Group 3: Apremilast Modified Release 8 | 4427.56 |
| Group 3: Apremilast Modified Release 9 | 4310.62 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | hours (Geometric Mean) |
|---|---|
| Group 3: Apremilast Immediate Release | 6.45 |
| Group 3: Apremilast Modified Release 8 | 6.58 |
| Group 3: Apremilast Modified Release 9 | 7.05 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Group 3: Apremilast Immediate Release | 378.59 |
| Group 3: Apremilast Modified Release 8 | 344.61 |
| Group 3: Apremilast Modified Release 9 | 334.51 |
"Relative bioavailability of each test formulation compared to the reference formulation corrected by dose, calculated as:~(AUC0-∞/Dose[test]) / (AUC0-∞/Dose[reference]) * 100%." (NCT02236988)
Timeframe: IR reference formulation: predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the first dose; MR formulations: predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, and 72 hours postdose.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Group 3: Apremilast Modified Release 8 | 45.64 |
| Group 3: Apremilast Modified Release 9 | 44.44 |
"Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.~Stool Frequency Subscore (SFS)~Rectal Bleeding Subscore~Endoscopy Subscore~Physician's Global Assessment (PGA)~Rectal bleeding (subscore 0-3) was defined as:~0 = No blood seen~= Streaks of blood with stool less than half the time~= Obvious blood with stool~= Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method." (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 46.6 |
| Apremilast 30 mg | 61.4 |
| Apremilast 40 mg | 67.3 |
A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain. (NCT02289417)
Timeframe: From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 5 |
| Apremilast 30 mg | 0 |
| Apremilast 40 mg | 1 |
A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain (NCT02289417)
Timeframe: From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any IP-related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious IP-related TEAE | Any TEAE Leading to IP Withdrawal | Any TEAE Leading to IP Interruption | Any TEAE Leading to Death | |
| Apremilast 30 mg | 28 | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
| Apremilast 40 mg | 36 | 20 | 1 | 1 | 0 | 1 | 0 | 0 |
| Placebo | 31 | 12 | 4 | 2 | 0 | 5 | 1 | 0 |
"Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores:~Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).~Two-sided 95% CI for the within-group proportions are based on the Wilson score method." (NCT02289417)
Timeframe: Week 8
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 48.3 |
| Apremilast 30 mg | 64.9 |
| Apremilast 40 mg | 81.8 |
A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain (NCT02289417)
Timeframe: From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Any TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious IP-related TEAE | Any TEAE Leading to IP Withdrawal | Any TEAE Leading to IP Interruption | Any TEAE Leading to Death | |
| Extension Phase: Apremilast 30 mg | 16 | 1 | 4 | 0 | 2 | 1 | 0 |
| Extension Phase: Apremilast 40 mg | 27 | 0 | 3 | 1 | 1 | 0 | 0 |
"Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease.~Stool Frequency Subscore (SFS)~Rectal Bleeding Subscore (RBS)~Endoscopy Subscore~Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method." (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 12.1 |
| Apremilast 30 mg | 31.6 |
| Apremilast 40 mg | 21.8 |
A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain (NCT02289417)
Timeframe: From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any TEAE | Any Severe TEAE | Any Serious TEAE | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Death | |
| Apremilast 30 mg | 60 | 5 | 6 | 3 | 1 | 0 |
| Apremilast 30 mg/Apremilast 40 mg | 8 | 0 | 1 | 1 | 0 | 0 |
| Apremilast 40 mg | 67 | 6 | 8 | 9 | 4 | 0 |
"The RBS was measured as:~0 = No blood seen~= Streaks of blood with stool less than half the time~= Obvious blood with stool most of the time~= Blood alone passes~The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method." (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 72.4 |
| Apremilast 30 mg | 84.2 |
| Apremilast 40 mg | 87.3 |
"An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12.~The MES subscore findings were defined as:~0 = Normal or inactive disease~= Mild Disease (erythema, decreased vascular pattern, mild friability)~= Moderate Disease (marked erythema, lack of vascular pattern, friability erosions)~= Severe Disease (spontaneous bleeding, ulceration)~The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method." (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 3.4 |
| Apremilast 30 mg | 8.8 |
| Apremilast 40 mg | 7.3 |
"An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as:~0 = Normal or inactive disease~= Mild Disease (erythema, decreased vascular pattern, mild friability)~= Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration).~The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method." (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 41.4 |
| Apremilast 30 mg | 73.7 |
| Apremilast 40 mg | 47.3 |
Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore > 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method. (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 19.0 |
| Apremilast 30 mg | 43.9 |
| Apremilast 40 mg | 27.3 |
"Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore >1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores:~Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease).~Two-sided 95% CI for the within-group proportions are based on the Wilson score method." (NCT02289417)
Timeframe: Week 8
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 32.8 |
| Apremilast 30 mg | 47.4 |
| Apremilast 40 mg | 52.7 |
"Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity.~The RBS was measured as:~0 = No blood seen~= Streaks of blood with stool less than half the time~= Obvious blood with stool most of the time~= Blood alone passes~The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method." (NCT02289417)
Timeframe: Week 12
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo | 46.6 |
| Apremilast 30 mg | 63.2 |
| Apremilast 40 mg | 67.3 |
Participants who were oral ulcer-free by week 6 and remained oral ulcer-free for at least 6 consecutive weeks during the 12-week placebo-controlled treatment phase. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 4.9 |
| Apremilast 30 mg BID | 29.8 |
Number of oral ulcers reported at the time of the first loss of complete response, ie, at the first instance when a participant had a reappearance of oral ulcers following a complete response, during the placebo-controlled treatment phase. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | oral ulcers (Least Squares Mean) |
|---|---|
| Placebo | 1.5 |
| Apremilast 30 mg BID | 1.1 |
"BD-related skin lesions (including acne-like lesions, folliculitis, and erythema nodosum) were evaluated according to the Static Physician's Global Assessment as follows:~Score 0 = clear skin. Score 1 = mild in severity with the presence of 1 to 10 lesions (papules, pustules, cysts) or nodules at any anatomical site.~Score 2 = Moderate severity; presence of 11 to 20 nodules or lesions (papules, pustules, cysts) at any anatomical site.~Score 3 = Severe; presence of > 20 nodules or lesions (papules, pustules, cysts) at any anatomical site.~The total sore was calculated as the sum of the acne-like lesions, folliculitis, and erythema nodosum scores, and therefore ranges from 0 to 9, where a higher score indicates a higher level of activity. A negative change from baseline indicates improvement." (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | scores on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.8 |
| Apremilast 30 mg BID | -0.9 |
"Pain of oral ulcers was measured using a 100 mm VAS scale. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was recorded.~A negative change from baseline indicates improvement." (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -15.9 |
| Apremilast 30 mg BID | -40.7 |
Pain of genital ulcers was measured using a 100 mm visual analog scale. The participant was asked to draw a single line perpendicular to the VAS line at the point that represented the severity of their pain during the previous week, with 0 mm (the left-hand end of the scale) representing no pain and 100 mm (the right-hand end of the scale) representing the worst pain imaginable. The distance of the perpendicular line from the left-hand end of the scale was recorded. A negative change from baseline indicates improvement. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | mm (Least Squares Mean) |
|---|---|
| Placebo | -24.5 |
| Apremilast 30 mg BID | -30.0 |
The Behçet's Syndrome Activity Score (BSAS) contains 10 questions that assess the number of new oral and genital ulcers and skin lesions, GI, CNS, vascular, and ocular involvement, and the participant's current level of discomfort. The Behçet's Syndrome Activity Score ranges from 0 to 100, with a higher score indicating a higher level of disease activity. A negative change from baseline indicates improvement. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -5.41 |
| Apremilast 30 mg BID | -17.35 |
The Behçet's Disease Current Activity Form (BDCAF) consists of 3 component scores: the Behçet's Disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The Patient's Perception of Disease Activity was assessed on a scale from 1 to 7, where a higher score indicates a higher level of disease activity and a negative change from baseline indicates improvement. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.7 |
| Apremilast 30 mg BID | -1.7 |
The Behçet's Disease Current Activity Form (BDCAF) consists of 3 component scores: the Behçet's disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The Clinician's Overall Perception of Disease Activity was assessed on a scale from 1 to 7, where a higher score indicates a higher level of disease activity and a negative change from baseline indicates improvement. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.7 |
| Apremilast 30 mg BID | -1.6 |
Time to oral ulcer resolution (defined as oral ulcer-free) was the time between the first dose date and the date when a complete response was achieved for the first time during the placebo-controlled treatment phase. For participants who did not achieve complete response or discontinued treatment before a complete response was achieved during the placebo-controlled treatment phase, time to event was censored at the last oral ulcer assessment date during the placebo-controlled treatment phase or the first dose date if there were no postbaseline ulcer assessments. Median and 95% confidence interval was based on Kaplan-Meier estimates. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Weeks (Median) |
|---|---|
| Placebo | 8.1 |
| Apremilast 30 mg BID | 2.1 |
The Behçet's Disease Current Activity Form (BDCAF) consists of 3 component scores: the Behçet's Disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The BDCAI consists of 12 questions regarding disease manifestations over the previous 4 weeks, including oral and genital disease activity, as well as other manifestations of BD involving the skin, joints, GI tract, eyes, nervous system, and vascular system. The BDCAI score is the sum score of 12 items and ranges from 0 to 12. A higher score indicates higher level of disease activity (worsening), and a negative change from baseline indicates improvement. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.4 |
| Apremilast 30 mg BID | -0.9 |
The Behçet's Disease Quality of Life questionnaire was developed to measure the influence of BD on a particpant's life. It consists of 30 self-completed itemized questions that measure disease-related restrictions on the participant's activities and their emotional response to these restrictions. The total score is the sum of all 30 items (each yes scores 1 and each no scores 0), with 0 representing no influence of Behçet's disease on a participant's quality of life and 30 representing the most severe influence. A negative change from baseline indicates improvement. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.5 |
| Apremilast 30 mg BID | -3.5 |
The number of oral ulcers that was counted for the analysis of the primary endpoint included current and recurrent ulcers at each time point; a single oral ulcer could be recounted multiple times if it persisted or recurred at subsequent visits. (NCT02307513)
Timeframe: Oral ulcers were assessed at weeks 0 (baseline), 1, 2, 4, 6, 8, 10, and 12 during the placebo-controlled period.
| Intervention | Ulcers*days (Least Squares Mean) |
|---|---|
| Placebo | 222.14 |
| Apremilast 30 mg BID | 129.54 |
"A TEAE is an adverse event (AE) with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. A serious AE (SAE) is any AE that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or constituted an important medical event. For both AEs and SAEs the investigator assessed the severity of the event according to the grading scale:~Mild: asymptomatic or with mild symptoms; Moderate: symptoms causing moderate discomfort and local or noninvasive intervention is indicated; Severe: symptoms causing severe discomfort or pain, symptoms requiring medical/surgical intervention." (NCT02307513)
Timeframe: From first dose of study drug in the placebo-controlled phase to the first dose of apremilast in the active treatment phase (12 weeks) or up to 28 days after last dose for participants who did not receive study drug at week 12, whichever was earlier.
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast 30 mg BID | 82 | 60 | 6 | 3 | 9 | 3 | 0 |
| Placebo | 74 | 37 | 6 | 4 | 6 | 5 | 0 |
"The apremilast-exposure period started on the date of the first dose of apremilast (week 0 for participants assigned to apremilast or week 12 for participants who were originally assigned to placebo and switched to apremilast at week 12) and ended 28 days after last dose in the active treatment phase.~An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. An SAE is any AE that resulted in death; was life-threatening; required or prolonged inpatient hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or constituted an important medical event. The investigator assessed the severity of each event according to the grading scale:~Mild: asymptomatic or mild symptoms; Moderate: symptoms causing moderate discomfort, local or noninvasive intervention indicated; Severe: symptoms causing severe discomfort or pain, requiring medical/surgical intervention (NCT02307513)
Timeframe: From first dose of apremilast (week 0 for those assigned to apremilast or week 12 for those assigned to placebo) up to 28 days after last dose; up to 56 weeks and 68 weeks in each arm respectively.
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Apremilast/Apremilast | 90 | 64 | 17 | 10 | 17 | 12 | 0 |
| Placebo/Apremilast | 70 | 29 | 4 | 7 | 10 | 3 | 0 |
Time to recurrence of oral ulcers following the loss of complete response (oral ulcer-free) was defined as the first instance when a participant had a reappearance of oral ulcers following a complete response, during the placebo-controlled treatment phase. For participants who did not have oral ulcer recurrence or discontinued treatment before any oral ulcer recurrence during the placebo-controlled treatment phase, time to event was censored at the last oral ulcer assessment during placebo-controlled treatment phase; For participants without any oral ulcer assessment following the first complete response, time to event was censored to the first complete response date. (NCT02307513)
Timeframe: Baseline through week 12
| Intervention | Weeks (Median) |
|---|---|
| Placebo | 2.3 |
| Apremilast 30 mg BID | 4.6 |
The definition includes participants who remained oral ulcer-free through week 12 after achieving a complete response (oral ulcer-free) prior to week 12. (NCT02307513)
Timeframe: Baseline to week 12
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 13.2 |
| Apremilast 30 mg BID | 31.3 |
A complete response at week 12 was defined as participants who were oral ulcer free at week 12. (NCT02307513)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 22.3 |
| Apremilast 30 mg BID | 52.9 |
A genital ulcer complete response at week 12 was defined as participants who were genital ulcer-free at week 12. (NCT02307513)
Timeframe: Week 12
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo | 41.2 |
| Apremilast 30 mg BID | 70.6 |
"Change from baseline in PPPASI at Week 16 for patients randomized to apremilast as compared to patients randomized to placebo~Palmoplantar psoriasis area severity index (PPPASI) is a scale that can vary from 0 to 72.~Erythema (E), induration (I), and desquamation (D) are evaluated on a scale of 0 to 4 while area is evaluated on a scale of 0 to 6. The combined score of each of these features, for the right (R) and left (L) palms and soles, gives a PPPASI score from 0 (absence of disease) to 72 (most severe palmoplantar psoriasis possible).~PPPASI = (E + I + D)Area X 0.2 (R palm) + (E + I + D) Area X 0.2 (L palm) + (E + I + D) Area X 0.3 (R sole) + (E + I + D) Area X 0.3 (L sole)" (NCT02400749)
Timeframe: 16 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -7.4 |
| Placebo Followed by Apremilast | -3.6 |
"Change from baseline in PPPASI at Week 32 for patients randomized to apremilast~Palmoplantar psoriasis area severity index (PPPASI) is a scale that can vary from 0 to 72.~Erythema (E), induration (I), and desquamation (D) are evaluated on a scale of 0 to 4 while area is evaluated on a scale of 0 to 6. The combined score of each of these features, for the right (R) and left (L) palms and soles, gives a PPPASI score from 0 (absence of disease) to 72 (most severe palmoplantar psoriasis possible).~PPPASI = (E + I + D)Area X 0.2 (R palm) + (E + I + D) Area X 0.2 (L palm) + (E + I + D) Area X 0.3 (R sole) + (E + I + D) Area X 0.3 (L sole)" (NCT02400749)
Timeframe: 32 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -11.3 |
"Change from baseline in mean PPPGA at Week 16 for patients randomized to apremilast as compared to patients randomized to placebo~The PPPGA is a zero to five, 6-point scale that evaluates the severity of palmoplantar psoriasis (score 0 [Clear]; score 1 [Almost clear]; score 2 [Mild]; score 3 [Moderate]; score 4 [Severe]; score 5 [Very severe])." (NCT02400749)
Timeframe: 16 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -0.8 |
| Placebo Followed by Apremilast | -0.4 |
"Change from baseline in PPPSA at Week 16 for patients randomized to apremilast as compared to patients randomized to placebo~The surface affected by psoriasis on palms and soles is estimated as a percentage of the total surface of palms and soles. Each palm represents 20% and each sole 30%. PPPSA values range from 0% (no psoriasis on palms and soles) to 100% (all palms and soles covered by psoriasis)." (NCT02400749)
Timeframe: 16 weeks
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -0.1 |
| Placebo Followed by Apremilast | 0.0 |
"Number of patients who achieve a PPPGA of 0 or 1 at Week 32 for patients randomized to apremilast~The PPPGA is a zero to five, 6-point scale that evaluates the severity of palmoplantar psoriasis (score 0 [Clear]; score 1 [Almost clear]; score 2 [Mild]; score 3 [Moderate]; score 4 [Severe]; score 5 [Very severe])." (NCT02400749)
Timeframe: 32 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 12 |
"Number of patients who achieve a PPPGA of 0 or 1 at Week 16 for patients randomized to apremilast as compared to patients randomized to placebo~The PPPGA is a zero to five, 6-point scale that evaluates the severity of palmoplantar psoriasis (score 0 [Clear]; score 1 [Almost clear]; score 2 [Mild]; score 3 [Moderate]; score 4 [Severe]; score 5 [Very severe])." (NCT02400749)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 7 |
| Placebo Followed by Apremilast | 2 |
PASI 90 or greater at week 36 (NCT02412644)
Timeframe: 36 weeks
| Intervention | participants (Number) |
|---|---|
| Apremilast + Apremilast | 1 |
| Apremilast + Placebo | 0 |
Analysis of Psoriasis Area Severity Index Score at week 36 to determine number of subjects who maintained PASI 75 at week 36 (NCT02412644)
Timeframe: 36weeks
| Intervention | participants (Number) |
|---|---|
| Apremilast + Apremilast | 4 |
| Apremilast + Placebo | 2 |
PGA score 0 or 1 (NCT02412644)
Timeframe: 36 weeks
| Intervention | participants (Number) |
|---|---|
| Apremilast + Apremilast | 1 |
| Apremilast + Placebo | 0 |
Psoriasis Area Severity Score of 75 or greater at week 12 (NCT02412644)
Timeframe: 12WEEKS
| Intervention | participants (Number) |
|---|---|
| Apremilast | 16 |
Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT02425826)
Timeframe: Date of first dose of apremilast during the placebo controlled phase or date of first dose of apremilast after week 16; overall maximum duration of exposure was 61.5 weeks during apremilast-exposure phase
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| ≥ At Least 1 TEAE | ≥ 1 Drug-related TEAE | ≥ At Least 1 Severe TEAE | ≥ At Least 1 Serious TEAE | ≥ 1 Serious Drug-related TEAE | ≥ 1 TEAE leading to drug withdrawal | ≥ 1 TEAE Leading to drug interruption | Any TEAE leading to death | |
| Apremilast | 142 | 98 | 5 | 10 | 1 | 14 | 27 | 0 |
The ScPGA will assess scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment with scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA is restricted to the participants with scalp involvement at baseline. (NCT02425826)
Timeframe: Week 16 to Week 52
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Responder status at Week 16 | Responder status maintained at Week 52 | |
| Apremilast | 50.0 | 80.4 |
The TSQM version II is an 11-question self-administered instrument to understand a participation's satisfaction with the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score mean indicates higher satisfaction with treatment. (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | units on a scale (Mean) | |||
|---|---|---|---|---|
| TSQM-Effectiveness | TSQM-Side Effects | TSQM-Convenience | TSQM-Global Satisfaction | |
| Apremilast | 57.25 | 78.50 | 66.93 | 63.24 |
| Placebo | 38.81 | 75.00 | 65.68 | 48.74 |
The TSQM version II is an 11-question self-administered instrument to understand a participants satisfaction on the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment. (NCT02425826)
Timeframe: Baseline to week 52
| Intervention | units on a scale (Mean) | |||
|---|---|---|---|---|
| TSQM-Effectiveness | TSQM-Side Effects | TSQM-Convenience | TSQM-Global Satisfaction | |
| Apremilast | 54.13 | 75.45 | 71.76 | 59.92 |
| Placebo-Apremilast | 57.68 | 77.29 | 72.74 | 59.24 |
"BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score. The range of BSA*sPGA mean percentage change from baseline to week 16 (end of phase) were -100 to 344.4 and -100 to 100 for the placebo and apremilast groups respectively. Higher scores represented worse outcomes." (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage change (Mean) |
|---|---|
| Placebo | -10.17 |
| Apremilast | -48.07 |
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 8.2 |
| Apremilast | 21.6 |
"DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best." (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | units on a scale (Mean) |
|---|---|
| Placebo | -2.4 |
| Apremilast | -4.8 |
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage change (Mean) |
|---|---|
| Placebo | -3.87 |
| Apremilast | -40.72 |
"BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand (entire palmar surface or handprint including the fingers), which equates to approximately 1% of total body surface area. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score." (NCT02425826)
Timeframe: Baseline to Week 52
| Intervention | percentage change (Mean) |
|---|---|
| Placebo-Apremilast | -42.23 |
| Apremilast | -55.45 |
The PtGA response rate is defined as the percentage of participants achieving 0 (clear) or 1 (very mild) on the PtGA scale at Week 16. The PtGA is the assessment by the participant of the overall disease severity at the time of evaluation. The PtGA is a 5-point scale ranging from 0 (clear) to 4 (severe). (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 20.5 |
| Apremilast | 33.8 |
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 6-point scale, ranging from 0 (clear) to 5 (very severe), with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are averaged and rounded to the nearest whole number to result in the final sPGA score. (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 9.6 |
| Apremilast | 30.4 |
Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT02425826)
Timeframe: From first dose of study drug to Week 16; maximum duration of exposure was 20.1 weeks during placebo controlled phase
| Intervention | participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| ≥ At Least 1 TEAE | ≥ 1 Drug-related TEAE | ≥ At Least 1 Severe TEAE | ≥ At Least 1 Serious TEAE | ≥ 1 Serious Drug-related TEAE | ≥ 1 TEAE leading to drug withdrawal | ≥ 1 TEAE Leading to drug interruption | Any TEAE leading to death | |
| Apremilast | 92 | 71 | 3 | 3 | 0 | 5 | 9 | 0 |
| Placebo | 35 | 21 | 1 | 0 | 0 | 3 | 3 | 0 |
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 24.7 |
| Apremilast | 53.4 |
The ScPGA assessed scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment. Scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA was restricted to the participants with scalp involvement at baseline. (NCT02425826)
Timeframe: Baseline to Week 16 (end of phase)
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 38.2 |
| Apremilast | 50.0 |
The Pruritus VAS assessment was conducted at the baseline visit and each post-baseline visit. The participant was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (0) represents no itch, and the right-hand boundary (100) represents itch as severe as can be imagined. The distance from the mark to the left-hand boundary will be recorded. The Pruritus VAS score ranges from 0 to 100. Higher scores correspond to more severe symptom. (NCT02425826)
Timeframe: Baseline to Weeks 1 and 16 (end of phase)
| Intervention | units on a scale (Mean) | |
|---|---|---|
| Week 1 | Week 16 | |
| Apremilast | -13.9 | -19.2 |
| Placebo | -9.6 | -10.2 |
A TEAE is an adverse event with a start date on or after the date of the first dose of apremilast and no later than 28 days after the last dose of apremilast. An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. A serious AE is any untoward AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization or in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or constitutes an important medical event. The investigator assessment of severity/intensity of an event was defined as mild, moderate or severe. (NCT02576678)
Timeframe: From first dose of apremilast until 28 days after the last dose; up to 29 July 2019; median treatment duration for adolescents apremilast 20 mg and 30 mg was 50.00 and 50.57 weeks respectively and for children was 50.00 weeks.
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug Related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious Drug-Related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Any TEAE Leading to Death | |
| Group 1 Adolescents: Apremilast 20 mg | 13 | 11 | 1 | 0 | 0 | 1 | 0 | 0 |
| Group 1 Adolescents: Apremilast 30 mg | 7 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Group 2 Children: Apremilast 20 mg | 20 | 17 | 1 | 1 | 0 | 4 | 2 | 0 |
Terminal-phase elimination half-life (t ½). PK parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | hours (Geometric Mean) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 5.418 |
| Group 1 Adolescents: Apremilast 30 mg | 6.775 |
| Group 2 Children: Apremilast 20 mg | 4.862 |
Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data. PK parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | hours (Median) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 2.467 |
| Group 1 Adolescents: Apremilast 30 mg | 3.000 |
| Group 2 Children: Apremilast 20 mg | 2.000 |
Apparent total plasma clearance (CL/F) of apremilast was calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | Liters/hour (Geometric Mean) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 11.113 |
| Group 1 Adolescents: Apremilast 30 mg | 10.338 |
| Group 2 Children: Apremilast 20 mg | 7.859 |
Area under the plasma concentration-time curve from time zero to the last quantifiable time point and was calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 1794.815 |
| Group 1 Adolescents: Apremilast 30 mg | 2900.472 |
| Group 2 Children: Apremilast 20 mg | 2367.641 |
Area under the plasma concentration-time curve from time zero to the 12 hours post dose was calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 1799.717 |
| Group 1 Adolescents: Apremilast 30 mg | 2901.795 |
| Group 2 Children: Apremilast 20 mg | 2544.874 |
Apparent total volume of distribution when dosed orally, based on study-state (Vss/F) or in the terminal phase (Vz/F). Pharmacokinetic parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | Liters (Geometric Mean) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 86.870 |
| Group 1 Adolescents: Apremilast 30 mg | 101.049 |
| Group 2 Children: Apremilast 20 mg | 55.126 |
Maximum observed plasma concentration (Cmax) of apremilast. PK parameters were calculated using non-compartmental methods, plasma concentrations and actual blood sampling times from the intensive sampling schedule. (NCT02576678)
Timeframe: For adolescents, a pre-dose sample prior to morning dose and on Day 14 as well as at hours 1, 2, 3, 5, 8 and 12 post dose; for the children, samples were collected 2 hours at predose (prior to morning dose) and at 2, 5 and 12 hours post morning dose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Group 1 Adolescents: Apremilast 20 mg | 274.272 |
| Group 1 Adolescents: Apremilast 30 mg | 410.929 |
| Group 2 Children: Apremilast 20 mg | 348.146 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to infinity was calculated as (AUC0-t + Ct/λz), where Ct is the last quantifiable concentration, and λz is the apparent terminal rate constant. (NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 3160 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 2760 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 3190 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. AUC from time zero to the last measured time point was calculated by the linear trapezoidal method. (NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 3130 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 2740 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 3160 |
Lag time is the delay between the time of administration and start of absorption. (NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | hours (Median) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 0.00 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 0.00 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 0.00 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 323 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 274 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 215 |
(NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | hours (Geometric Mean) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 7.89 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 8.51 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 7.54 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | hours (Median) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 2.00 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 2.00 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 5.00 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology.~A treatment-emergent AE (TEAE) was defined as any AE that occurred after dosing of the study drug.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event." (NCT02641353)
Timeframe: From first dose of study drug in treatment period 1 to 8 days after the last dose; up to 18 days.
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAEs related to study drug | Serious adverse events | TEAEs leading to discontinuation | TEAEs leading to death | |
| Treatment A: Apremilast 30 mg Tablet - Fasted | 8 | 4 | 0 | 0 | 0 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 10 | 7 | 0 | 0 | 0 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 6 | 4 | 0 | 0 | 0 |
(NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | L (Geometric Mean) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 108 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 133 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 102 |
(NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | L/h (Geometric Mean) |
|---|---|
| Treatment A: Apremilast 30 mg Tablet - Fasted | 9.51 |
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 10.9 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 9.42 |
Relative bioavailability of the oral suspension formulation compared to the tablet formulation, calculated as (AUC0-∞/Dose[oral suspension]) / (AUC0-∞/Dose[tablet]) * 100%. (NCT02641353)
Timeframe: Predose and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60 and 72 hours after dosing on day 1 of each treatment period.
| Intervention | percent availability (Geometric Mean) |
|---|---|
| Treatment B: Apremilast 30 mg Oral Suspension - Fasted | 87.6 |
| Treatment C: Apremilast 30 mg Oral Suspension - Fed | 101 |
Change from Baseline in the Alopecia Areata Symptom Impact Scale (AASIS) at Weeks 24 and Week 48 The AASIS is a 13-items disease-specific patient-reported outcomes measure that asks participants about symptoms related to alopecia areata and how these symptoms interfere with daily functioning. Total scale ranges from 0-130, with higher score indicating more symptoms. (NCT02684123)
Timeframe: Week 24 and Weeks 48
| Intervention | score on a scale (Mean) | ||
|---|---|---|---|
| Baseline | Week 24 | week 48 | |
| Placebo | 51.4 | 53.57 | 75.67 |
Number of subjects achieving an alopecia areata Physician's Global Assessment (aaPGA) score of 3 or above at Weeks 24 (0, no regrowth; 1, <25% of regrowth; 2, 25%-49% of regrowth; 3, 50%-74% of regrowth; 4, 75%-99% of re- growth; 5, 100% of regrowth). (NCT02684123)
Timeframe: Week 24 and Week 48
| Intervention | Participants (Count of Participants) | |
|---|---|---|
| week 24 | week 48 | |
| Apremilast | 1 | 0 |
| Placebo | 1 | 1 |
Semiquantitative score using SALT subclasses (0, no hair loss; 1, <25% hair loss; 2, 25%-49% hair loss; 3, 50%-74% hair loss; 4, 75%-99% hair loss; 5, 100% hair loss) at week 24 and week 48 compared to baseline (NCT02684123)
Timeframe: Baseline, Week 24 and Weeks 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Baseline | Week 24 | |
| Apremilast | 4.35 | 4.42 |
Semiquantitative score using SALT subclasses (0, no hair loss; 1, <25% hair loss; 2, 25%-49% hair loss; 3, 50%-74% hair loss; 4, 75%-99% hair loss; 5, 100% hair loss) at week 24 and week 48 compared to baseline (NCT02684123)
Timeframe: Baseline, Week 24 and Weeks 48
| Intervention | score on a scale (Mean) | ||
|---|---|---|---|
| Baseline | Week 24 | week 48 | |
| Placebo | 4.3 | 4.1 | 3.67 |
"Change from baseline in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 24 and Weeks 48.~Total scale from 0 to 100, with higher score indicating better quality of life." (NCT02684123)
Timeframe: Baseline, Week 24 and Weeks 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Baseline | Week 24 | |
| Apremilast | 30.75 | 29.55 |
"Number of patients achieving 50% or greater improvement in their Severity of Alopecia Tool (SALT) score (SALT50) at Week 24~SALT50 is defined as the percent of patients achieving >=50% reduction in SALT score compared to baseline.~Scalp is divided into 4 areas namely, Vertex - 40% (0.4) of scalp surface area; right profile of scalp - 18% (0.18) of scalp surface area; left profile of scalp - 18% (0.18) of scalp surface area; Posterior aspect of scalp - 24% (0.24) of scalp surface area. Percentage of hair loss in any of these areas is percentage hair loss multiplied by percent surface area of the scalp in that area. SALT score is the sum of percentage of hair loss in all above mentioned areas." (NCT02684123)
Timeframe: Baseline and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 1 |
| Placebo | 1 |
Mean percent change in SALT score at 4, 8, 12, 16, 20, and 24 weeks as compared to baseline (NCT02684123)
Timeframe: Baseline and week 4, 8, 12, 16, 20, 24
| Intervention | Mean percent change (Mean) | |||||
|---|---|---|---|---|---|---|
| Week 4 | Week 8 | Week 12 | Week 16 | Week 20 | Week 24 | |
| Apremilast | -0.13 | -2.39 | -0.99 | -8.15 | 1.17 | -1.45 |
| Placebo | -0.11 | -2.86 | -4.07 | -10.55 | -9.92 | -9.01 |
"Change from baseline in the Alopecia Areata Quality of Life questionnaire (AA-QoL) at Weeks 24 and Weeks 48.~Total scale from 0 to 100, with higher score indicating better quality of life." (NCT02684123)
Timeframe: Baseline, Week 24 and Weeks 48
| Intervention | score on a scale (Mean) | ||
|---|---|---|---|
| Baseline | Week 24 | week 48 | |
| Placebo | 34.0 | 27.14 | 35.33 |
Change from Baseline in the Alopecia Areata Symptom Impact Scale (AASIS) at Weeks 24 and Week 48 The AASIS is a 13-items disease-specific patient-reported outcomes measure that asks participants about symptoms related to alopecia areata and how these symptoms interfere with daily functioning. Total scale ranges from 0-130, with higher score indicating more symptoms. (NCT02684123)
Timeframe: Week 24 and Weeks 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Baseline | Week 24 | |
| Apremilast | 56.79 | 48.0 |
(NCT02777554)
Timeframe: Apremilast IR: Predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg IR BID (Fasted) | 7030 |
| Part 2: Apremilast 75 mg XL (Fasted) | 6650 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | 7580 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | 7400 |
(NCT02777554)
Timeframe: Apremilast IR: Predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg IR BID (Fasted) | 379 |
| Part 2: Apremilast 75 mg XL (Fasted) | 402 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | 436 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | 496 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology.~A serious AE is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event. The Investigator determined the relationship between the administration of study drug and the occurrence of each AE as Not Suspected or Suspected as defined in the Protocol." (NCT02777554)
Timeframe: Part 1: Up to 7 days after last dose in each treatment period (14 days); Part 2: Up to 7 days after each dose.
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE related to study drug | Serious adverse events | Serious adverse events related to study drug | TEAE leading to discontinuation | TEAE related to study drug leading to discontinuation | Deaths | |
| Part 1: Apremilast 30 mg IR BID | 50 | 45 | 0 | 0 | 3 | 3 | 0 |
| Part 1: Apremilast 75 mg XL QD | 47 | 41 | 0 | 0 | 5 | 5 | 0 |
| Part 2: Apremilast 30 mg IR BID (Fasted) | 2 | 2 | 0 | 0 | 1 | 1 | 0 |
| Part 2: Apremilast 75 mg XL (Fasted) | 4 | 3 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | 3 | 2 | 0 | 0 | 0 | 0 | 0 |
(NCT02777554)
Timeframe: Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Part 1: Apremilast 30 mg IR BID | 6370 |
| Part 1: Apremilast 75 mg XL QD | 6090 |
(NCT02777554)
Timeframe: Apremilast IR: Day 7 predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, and 24 hours after the morning dose. Apremilast XL: Day 7 predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, and 24 hours after the morning dose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Part 1: Apremilast 30 mg IR BID | 451 |
| Part 1: Apremilast 75 mg XL QD | 459 |
(NCT02777554)
Timeframe: Apremilast IR: Predose and at 0.5, 1, 2, 3, 5, 8, 12, 12.5, 13, 14, 15, 17, 20, 24, 36, 48, 60, and 72 hours after the morning dose. Apremilast XL: Predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 20, 24, 30, 36, 48, 60, and 72 hours postdose.
| Intervention | ng*h/mL (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg IR BID (Fasted) | 7100 |
| Part 2: Apremilast 75 mg XL (Fasted) | 6680 |
| Part 2: Apremilast 75 mg XL (Standard Meal) | 7600 |
| Part 2: Apremilast 75 mg XL (High Fat Meal) | 7450 |
(NCT02802735)
Timeframe: Part 1, up to 40 days; Part 2, up to 24 days
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE related to study drug | Serious adverse events | Serious adverse events related o study dug | TEAE leading to discontinuation | Treatment-related TEAE leading to discontinuation | Deaths | |
| Part 1: Apremilast 20 mg | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Apremilast 30 mg | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Apremilast 40 mg | 3 | 2 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Apremilast 30 mg BID | 7 | 6 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Placebo BID | 3 | 2 | 0 | 0 | 0 | 0 | 0 |
Area under the plasma concentration-time curve during a dosage interval (tau) at steady state, where tau is 12 hours. (NCT02802735)
Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose
| Intervention | ng*hr/mL (Geometric Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Part 2: Apremilast 30 mg BID | 1610 | 2600 |
(NCT02802735)
Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose
| Intervention | ng/mL (Geometric Mean) | |
|---|---|---|
| Day 1 | Day 14 | |
| Part 2: Apremilast 30 mg BID | 283 | 408 |
(NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Part 1: Apremilast 20 mg | 1790 |
| Part 1: Apremilast 30 mg | 2360 |
| Part 1: Apremilast 40 mg | 3500 |
(NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|---|
| Part 1: Apremilast 20 mg | 1770 |
| Part 1: Apremilast 30 mg | 2330 |
| Part 1: Apremilast 40 mg | 3470 |
Concentrations of apremilast in plasma were measured using a validated liquid chromatography tandem mass spectrometry assay. (NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | ng/mL (Geometric Mean) |
|---|---|
| Part 1: Apremilast 20 mg | 205 |
| Part 1: Apremilast 30 mg | 273 |
| Part 1: Apremilast 40 mg | 373 |
(NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | hours (Geometric Mean) |
|---|---|
| Part 1: Apremilast 20 mg | 7.4 |
| Part 1: Apremilast 30 mg | 8.2 |
| Part 1: Apremilast 40 mg | 7.4 |
(NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | hours (Median) |
|---|---|
| Part 1: Apremilast 20 mg | 3.0 |
| Part 1: Apremilast 30 mg | 3.0 |
| Part 1: Apremilast 40 mg | 2.0 |
(NCT02802735)
Timeframe: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose
| Intervention | liters/hour (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg BID | 11.5 |
(NCT02802735)
Timeframe: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose
| Intervention | liters (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg BID | 130 |
Ratio of accumulation calculated as Day 14 AUC0-τ / Day 1 AUC0-τ (NCT02802735)
Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose, and on day 14 only at 24, 36, 48, 60, and 72 hours after the morning dose
| Intervention | ratio (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg BID | 1.62 |
(NCT02802735)
Timeframe: Day 1 and day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, and 12 hours after the morning dose
| Intervention | hours (Median) | |
|---|---|---|
| Day 1 | Day 14 | |
| Part 2: Apremilast 30 mg BID | 2.00 | 1.50 |
(NCT02802735)
Timeframe: Day 14 prior to the morning dose (0 hour), and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours after the morning dose
| Intervention | hours (Geometric Mean) |
|---|---|
| Part 2: Apremilast 30 mg BID | 7.80 |
(NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | liters/hour (Geometric Mean) |
|---|---|
| Part 1: Apremilast 20 mg | 11.1 |
| Part 1: Apremilast 30 mg | 12.7 |
| Part 1: Apremilast 40 mg | 11.4 |
(NCT02802735)
Timeframe: Day 1 of each treatment period at predose (0 hour) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 24, 36, 48, 60, and 72 hours post-dose.
| Intervention | liters (Geometric Mean) |
|---|---|
| Part 1: Apremilast 20 mg | 120 |
| Part 1: Apremilast 30 mg | 151 |
| Part 1: Apremilast 40 mg | 122 |
The Subject Assessments of pruritis is measured at screening, baseline, and weeks 4, 8 and 16. Each subject rates the severity of their itching over the last 24 hours on a 10-point scale from 0 (none) to 10 (unbearable) (NCT03000309)
Timeframe: Baseline to Week 16
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -3 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. Static Physician Global Assessment (sPGA) of disease severity is measured by the Investigator on a 6-point scale wherein 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, 4=Severe, 5=Very Severe. The product of these values offers a more specific assessment of the severity of psoriasis. This product can yield a result between 0 (no disease) and 500 (most severe disease) By reporting the percent change as well as the absolute value change, the reader may be better able to appreciate the impact on disease severity of the medication under study. (NCT03000309)
Timeframe: Week 16
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | -9 |
The Dermatology Life Quality Index (DLQI) is a 10-question survey administered to subjects in order to ascertain the extent to which psoriasis has affected the patient's life in the week prior to completing the questionnaire. The score is a sum of the value of each answer wherein Very Much=3, A lot=2, A little=1 and Not at all=0. 0 is the lowest possible score and indicates no impact of disease on quality of life. 30 is the highest possible score and indicates the most negative impact of disease on quality of life. (NCT03000309)
Timeframe: Week 8
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | -6 |
The Dermatology Life Quality Index (DLQI) is a 10-question survey administered to subjects in order to ascertain the extent to which psoriasis has affected the patient's life in the week prior to completing the questionnaire. The score is a sum of the value of each answer wherein Very Much=3, A lot=2, A little=1 and Not at all=0. 0 is the lowest possible score and indicates no impact of disease on quality of life. 30 is the highest possible score and indicates the most negative impact of disease on quality of life. (NCT03000309)
Timeframe: Week 16
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -7 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. This will be assessed at screening, baseline, and weeks 4, 8 and 16 (NCT03000309)
Timeframe: Week 16
| Intervention | percentage of body surface area affected (Mean) |
|---|---|
| Apremilast | -2 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. This will be assessed at screening, baseline, and weeks 4, 8 and 16 (NCT03000309)
Timeframe: Baseline to Week 8
| Intervention | percentage of body surface area affected (Mean) |
|---|---|
| Apremilast | -1 |
The Psoriasis Area Severity index (PASI) is performed at screening, baseline, and weeks 4, 8 and 16. This tool is used to measure the severity and extent of disease by combining the assessment of severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease.) (NCT03000309)
Timeframe: Week 8
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 10 |
The Psoriasis Area Severity index (PASI) is performed at screening, baseline, and weeks 4, 8 and 16. This tool is used to measure the severity and extent of disease by combining the assessment of severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease.) (NCT03000309)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 9 |
The Subject Assessments of pruritis is measured at screening, baseline, and weeks 4, 8 and 16. Each subject rates the severity of their itching over the last 24 hours on a 10-point scale from 0 (none) to 10 (unbearable) (NCT03000309)
Timeframe: Baseline to Week 8
| Intervention | units on a scale (Mean) |
|---|---|
| Apremilast | -3 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. This will be assessed at screening, baseline, and weeks 4, 8 and 16 (NCT03000309)
Timeframe: Baseline to Week 16
| Intervention | percent change (Mean) |
|---|---|
| Apremilast | -36 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. This will be assessed at screening, baseline, and weeks 4, 8 and 16 (NCT03000309)
Timeframe: Baseline to Week 8
| Intervention | percent change (Mean) |
|---|---|
| Apremilast | -19 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. Static Physician Global Assessment (sPGA) is measured by the Investigator on a 6-point scale wherein 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, 4=Severe, 5=Very Severe. Th3 product of these values offers a more specific assessment of the severity of psoriasis. This product may yield a result between 0 (no disease) and 500 (most severe disease.) (NCT03000309)
Timeframe: Week 8
| Intervention | percent change (Mean) |
|---|---|
| Apremilast | -29 |
The area of body surface affected by psoriasis (BSA) will be estimated by the Investigator as a percentage of the subject's total body surface area wherein the area of the subject's palm will be considered as 1% of total BSA. Static Physician Global Assessment (sPGA) is measured by the Investigator on a 6-point scale wherein 0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, 4=Severe, 5=Very Severe. The product of these values offers a more specific assessment of the severity of psoriasis. This product can yield a result between 0(no disease) and 500 (most severe disease.) By reporting the percent change as well as the absolute value change, the reader may be better able to appreciate the impact on disease severity of the medication under study. (NCT03000309)
Timeframe: Week 16
| Intervention | percent change (Mean) |
|---|---|
| Apremilast | -44 |
The Psoriasis Area Severity index (PASI) is performed at screening, baseline, and weeks 4, 8 and 16. This tool is used to measure the severity and extent of disease by combining the assessment of severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease.) (NCT03000309)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 8 |
The Psoriasis Area Severity index (PASI) is performed at screening, baseline, and weeks 4, 8 and 16. This tool is used to measure the severity and extent of disease by combining the assessment of severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease.) (NCT03000309)
Timeframe: Week 8
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 3 |
The Psoriasis Area Severity index (PASI) is performed at screening, baseline, and weeks 4, 8 and 16. This tool is used to measure the severity and extent of disease by combining the assessment of severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease.) (NCT03000309)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 6 |
The Psoriasis Area Severity index (PASI) is performed at screening, baseline, and weeks 4, 8 and 16. This tool is used to measure the severity and extent of disease by combining the assessment of severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease.) (NCT03000309)
Timeframe: Week 8
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast | 0 |
mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.) (NCT03022617)
Timeframe: 36 weeks
| Intervention | percentage of reduction in mNAPSI score (Mean) |
|---|---|
| Study Group | 64.1 |
HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.953 |
| Week 52 vs. Week 16 | 1.092 |
HDL-C is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.842 |
| Week 52 vs. Week 16 | 1.711 |
GlycA is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 4.324 |
| Week 52 vs. Week 16 | -8.703 |
Glucose is a marker of glucose metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 8.032 |
| Week 52 vs. Week 16 | 2.604 |
Fetuin A is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -53.518 |
| Week 52 vs. Week 16 | 36.686 |
Ferritin is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -22.645 |
| Week 52 vs. Week 16 | -1.736 |
DRI is a marker of glucose metabolism. DRI is a nuclear magnetic resonance spectroscopy (NMR)-derived multimarker score (values 1-100) that predicts a patient's risk of developing type 2 diabetes mellitus (T2D) independent of glycemic status. DRI derives its performance from the weighted addition of the Lipoprotein Insulin Resistance Index (LP-IR) scores with simultaneously-measured levels of branched-chain amino acids (BCAA). Higher scores indicate greater risk. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | index (Mean) |
|---|---|
| Week 52 vs. Baseline | -2.834 |
| Week 52 vs. Week 16 | 1.765 |
CRP is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 36.050 |
| Week 52 vs. Week 16 | -246.058 |
Citrate is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -5.547 |
| Week 52 vs. Week 16 | -4.766 |
Cholesterol Efflux Capacity is a marker of lipid function and metabolism. The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: [(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)]. Cholesterol efflux capacity is inversely correlated with incidence of cardiovascular events (i.e. higher cholesterol efflux capacity is better for patients). (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | unitless measure (Mean) |
|---|---|
| Week 52 vs. Baseline | -0.159 |
| Week 52 vs. Week 16 | -0.111 |
Beta Hydroxybutyrate is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -48.450 |
| Week 52 vs. Week 16 | -38.228 |
BCAA is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -24.353 |
| Week 52 vs. Week 16 | 12.785 |
ApoB is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 2.225 |
| Week 52 vs. Week 16 | 3.360 |
ApoA1 is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 5.792 |
| Week 52 vs. Week 16 | 5.272 |
Alanine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 23.209 |
| Week 52 vs. Week 16 | 39.496 |
Adiponectin is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -2.106 |
| Week 52 vs. Week 16 | 1.268 |
Acetone is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -32.489 |
| Week 52 vs. Week 16 | -10.939 |
Acetoacetic Acid is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.616 |
| Week 52 vs. Week 16 | 0.993 |
VS-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 0.445 |
VLDL-Z is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nm (Mean) |
|---|---|
| Apremilast | -1.607 |
VLDL-TG is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | -4.393 |
VL-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -0.000 |
VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 1.227 |
VL-LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -18.678 |
VCAM-1 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Apremilast | -11.201 |
Valine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -14.301 |
TNF-alpha is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | 17.914 |
TRLTG is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | -5.142 |
Triglyceride is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | -3.542 |
Total Cholesterol is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | 0.254 |
S-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | 0.507 |
SAA is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Apremilast | 46.047 |
S-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 1.371 |
S-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 0.534 |
S-LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -31.780 |
MCP-1 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | 3.056 |
M-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -0.203 |
M-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 0.625 |
M-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 0.115 |
LDL-C is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | 0.119 |
LM-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -0.214 |
LP-IR is a marker of glucose metabolism. LP-IR is a marker of insulin resistance, and as such the LP-IR score predicts a patient's likelihood of future development of type 2 diabetes. LP-IR is a multimarker index (values 0-100) based on the concentrations of particular lipoprotein subclasses. Greater score indicates higher likelihood of developing diabetes. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | index (Mean) |
|---|---|
| Apremilast | -0.763 |
Leucine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -9.185 |
Leptin is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Apremilast | -84.193 |
LDL-Z is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nm (Mean) |
|---|---|
| Apremilast | 0.086 |
LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -21.712 |
LM-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -0.442 |
L-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -0.231 |
L-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -0.900 |
L-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -0.811 |
L-LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | 21.763 |
Ketone Bodies are markers of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -30.319 |
IDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | -11.763 |
IL-1b is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | -0.472 |
IFN-gamma is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | -1.944 |
ICAM-1 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Apremilast | -169.902 |
Insulin is a marker of glucose metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Apremilast | 159.448 |
IL2RA is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Apremilast | -3.308 |
IL-9 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | -0.090 |
IL-8 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | 24.014 |
IL-6 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | 2.727 |
IL-17A is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | -0.947 |
IL-10 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Apremilast | -0.054 |
HOMA-IR is a marker of glucose metabolism. HOMA-IR, a method used to quantify insulin resistance and beta-cell function, is expressed using fasting blood glucose and insulin levels. It is calculated using the formula (HOMA-IR = fasting glucose [mg/dl] * fasting insulin [mU/ml]/405). (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | index (Mean) |
|---|---|
| Apremilast | 0.551 |
HDL-C is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | 0.136 |
HDL-Z is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nm (Mean) |
|---|---|
| Apremilast | -0.071 |
HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | 0.058 |
GlycA is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | 10.690 |
Glucose is a marker of metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | 2.615 |
Fetuin A is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Apremilast | -50.732 |
Ferritin is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Apremilast | -13.416 |
DRI is a marker of glucose metabolism. DRI is a nuclear magnetic resonance spectroscopy (NMR)-derived multimarker score (values 1-100) that predicts a patient's risk of developing type 2 diabetes mellitus (T2D) independent of glycemic status. DRI derives its performance from the weighted addition of the Lipoprotein Insulin Resistance Index (LP-IR) scores with simultaneously-measured levels of branched-chain amino acids (BCAA). Higher scores indicate greater risk. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | index (Mean) |
|---|---|
| Apremilast | -2.978 |
Citrate is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | 0.429 |
"Cholesterol Efflux Capacity is a marker of lipid function and metabolism.~The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: [(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)]. Cholesterol efflux capacity is inversely correlated with incidence of cardiovascular events (i.e. higher cholesterol efflux capacity is better for patients)." (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | unitless measure (Mean) |
|---|---|
| Apremilast | -0.010 |
CRP is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Apremilast | -414.175 |
Beta Hydroxybutyrate is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -13.859 |
Branched-chain amino acids (BCAA) is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -29.505 |
ApoB is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | 0.308 |
ApoA1 is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | 0.939 |
Alanine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -20.059 |
Adiponectin is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Apremilast | -1.430 |
Acetone is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -17.171 |
Acetoacetic Acid is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | 0.711 |
TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Apremilast | 0.283 |
TRLC is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Apremilast | -0.352 |
"Secondary analysis will consist of comparisons of change in Pruritus VAS scores.~A visual analogue scale for pruritus (itch), ranging from 0 (no itch) to 100 (worst imaginable itch)." (NCT03082729)
Timeframe: Baseline, week 16, and week 52.
| Intervention | score on a scale (Mean) |
|---|---|
| Week 16 vs. Baseline | -27.527 |
| Week 52 vs. Baseline | -19.110 |
Secondary analysis will consist of comparisons of change in PGA scores. Physician Global Assessment (PGA) is calculated by averaging three subcomponent scores (induration, erythema, and scaling) that are graded from 0 (no involvement) to 5 (maximum involvement) that are averaged over all psoriatic lesions. Higher scores indicate greater disease burden. (NCT03082729)
Timeframe: Baseline, week 16, and week 52.
| Intervention | score on a scale (Mean) |
|---|---|
| Week 16 vs. Baseline | -1.200 |
| Week 52 vs. Baseline | -1.067 |
Secondary analysis will consist of comparisons of change in PASI scores. PASI is the most widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). (NCT03082729)
Timeframe: Baseline, week 16, and week 52.
| Intervention | score on a scale (Mean) |
|---|---|
| Week 16 vs. Baseline | -10.778 |
| Week 52 vs. Baseline | -9.903 |
Secondary analysis will consist of comparisons of vascular inflammation of the five aortic segments using TBR between week 52, 16, and baseline. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | ratio (Mean) | ||||
|---|---|---|---|---|---|
| Ascending aorta | Aortic arch | Descending aorta | Abdominal aorta (suprarenal) | Abdominal aorta (infrarenal) | |
| Week 16 vs. Baseline | -0.067 | -0.062 | -0.000 | -0.026 | -0.030 |
| Week 52 vs. Baseline | -0.099 | -0.080 | -0.057 | -0.075 | -0.118 |
| Week 52 vs. Week 16 | 0.028 | 0.010 | -0.019 | -0.017 | -0.038 |
L-LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 25.105 |
| Week 52 vs. Week 16 | -1.658 |
Valine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -12.589 |
| Week 52 vs. Week 16 | 6.269 |
"Secondary analysis will consist of comparisons of change in body composition between weeks 52, 16, and baseline. Visceral adipose tissue quantification using a single CT slice at the level of the umbilicus using computer-assisted tissue segmentation (Pescatori LC et al. Quantification of visceral adipose tissue by computed tomography and magnetic resonance imaging: reproducibility and accuracy. Radiol Bras. 2019 15(1):1-6.).~The values represent the cross-sectional area of the tissue segmented on the CT slice (cm^2); higher values indicate greater amount of visceral adipose tissue." (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | cm^2 (Mean) |
|---|---|
| Week 16 vs. Baseline | -10.681 |
| Week 52 vs. Baseline | -12.519 |
| Week 52 vs. Week 16 | 2.189 |
"Secondary analysis will consist of comparisons of change in body composition between weeks 52, 16, and baseline. Subcutaneous adipose tissue quantification using a single CT slice at the level of the umbilicus using computer-assisted tissue segmentation (Pescatori LC et al. Quantification of visceral adipose tissue by computed tomography and magnetic resonance imaging: reproducibility and accuracy. Radiol Bras. 2019 15(1):1-6.).~The values represent the cross-sectional area of the tissue segmented on the CT slice (cm^2); higher values indicate greater amount of subcutaneous adipose tissue." (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | cm^2 (Mean) |
|---|---|
| Week 16 vs. Baseline | -19.857 |
| Week 52 vs. Baseline | -19.585 |
| Week 52 vs. Week 16 | 0.638 |
Secondary analysis will consist of comparisons of total vascular inflammation of the aorta using TBR between week 52, 16, and baseline. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | ratio (Mean) |
|---|---|
| Week 52 vs. Baseline | -0.069 |
| Week 52 vs. Week 16 | -0.016 |
The primary analysis will consist of comparisons of total vascular inflammation of the aorta between week 16 and baseline using [18F]-Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) / Computed Tomography (CT) (FDG-PET/CT). Tissue-to-background ratio (TBR) of the standardized uptake value (SUV) is used to assess the level of inflammation of the aorta relative to the venous blood pool (background reference). (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | ratio (Mean) |
|---|---|
| Apremilast | -0.017 |
Isoleucine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 16 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Apremilast | -6.018 |
IL-6 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 22.680 |
| Week 52 vs. Week 16 | 18.344 |
IL-1b is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.285 |
| Week 52 vs. Week 16 | 0.624 |
IL-17A is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -1.383 |
| Week 52 vs. Week 16 | 0.141 |
IL-10 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.631 |
| Week 52 vs. Week 16 | 0.689 |
IFN-gamma is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.281 |
| Week 52 vs. Week 16 | 4.717 |
IDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -12.316 |
| Week 52 vs. Week 16 | 18.211 |
ICAM-1 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 41.059 |
| Week 52 vs. Week 16 | 292.802 |
HOMA-IR is a marker of glucose metabolism. HOMA-IR, a method used to quantify insulin resistance and beta-cell function, is expressed using fasting blood glucose and insulin levels. It is calculated using the formula (HOMA-IR = fasting glucose [mg/dl] * fasting insulin [mU/ml]/405). (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | index (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.814 |
| Week 52 vs. Week 16 | 0.753 |
HDL-Z is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nm (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.053 |
| Week 52 vs. Week 16 | 0.089 |
Secondary analysis will consist of comparisons of change in DLQI scores. DLQI is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. The score ranges from 0 to 30; 0-1 = No effect on patient's life, 2-5 = Small effect, 6-10 = Moderate effect, 11-20 = Very large effect, 21-30 = Extremely large effect. (NCT03082729)
Timeframe: Baseline, week 16, and week 52.
| Intervention | score on a scale (Mean) |
|---|---|
| Week 16 vs. Baseline | -6.050 |
| Week 52 vs. Baseline | -5.692 |
VS-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.619 |
| Week 52 vs. Week 16 | 7.361 |
VLDL-Z is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nm (Mean) |
|---|---|
| Week 52 vs. Baseline | -0.039 |
| Week 52 vs. Week 16 | 3.113 |
VLDL-TG is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 3.553 |
| Week 52 vs. Week 16 | 10.458 |
VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 4.934 |
| Week 52 vs. Week 16 | 0.645 |
VL-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -0.003 |
| Week 52 vs. Week 16 | -0.002 |
VL-LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 9.605 |
| Week 52 vs. Week 16 | 71.605 |
VCAM-1 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 10.253 |
| Week 52 vs. Week 16 | 24.967 |
TRLTG is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 4.520 |
| Week 52 vs. Week 16 | 14.465 |
TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 5.539 |
| Week 52 vs. Week 16 | 8.555 |
TRLC is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.547 |
| Week 52 vs. Week 16 | 2.598 |
Triglyceride is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 4.684 |
| Week 52 vs. Week 16 | 12.526 |
Total Cholesterol is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 4.316 |
| Week 52 vs. Week 16 | 7.474 |
TNF-alpha is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 100.589 |
| Week 52 vs. Week 16 | 72.650 |
SAA is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 1586.025 |
| Week 52 vs. Week 16 | 2799.836 |
S-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 2.913 |
| Week 52 vs. Week 16 | -1.842 |
S-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 2.714 |
| Week 52 vs. Week 16 | -2.990 |
S-LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -9.184 |
| Week 52 vs. Week 16 | 53.605 |
S-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.434 |
| Week 52 vs. Week 16 | 0.118 |
MCP-1 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 101.704 |
| Week 52 vs. Week 16 | 78.605 |
M-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.753 |
| Week 52 vs. Week 16 | 1.008 |
M-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.976 |
| Week 52 vs. Week 16 | 2.204 |
M-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.203 |
| Week 52 vs. Week 16 | 0.500 |
LP-IR is a marker of glucose metabolism. LP-IR is a marker of insulin resistance, and as such the LP-IR score predicts a patient's likelihood of future development of type 2 diabetes. LP-IR is a multimarker index (values 0-100) based on the concentrations of particular lipoprotein subclasses. Greater score indicates higher likelihood of developing diabetes. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | index (Mean) |
|---|---|
| Week 52 vs. Baseline | -1.158 |
| Week 52 vs. Week 16 | 2.684 |
LM-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.676 |
| Week 52 vs. Week 16 | 2.432 |
LM-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.595 |
| Week 52 vs. Week 16 | 1.061 |
Leucine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -8.223 |
| Week 52 vs. Week 16 | 1.313 |
Leptin is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -498.841 |
| Week 52 vs. Week 16 | 304.320 |
LDL-Z is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nm (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.037 |
| Week 52 vs. Week 16 | -0.118 |
LDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 5.605 |
| Week 52 vs. Week 16 | 78.105 |
LDL-C is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | mg/dL (Mean) |
|---|---|
| Week 52 vs. Baseline | 1.158 |
| Week 52 vs. Week 16 | 4.737 |
L-VLDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.095 |
| Week 52 vs. Week 16 | 1.724 |
L-TRLP is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | nmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.233 |
| Week 52 vs. Week 16 | 1.981 |
L-HDL-P is a marker of lipid function and metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | 0.332 |
| Week 52 vs. Week 16 | 0.503 |
Ketone Bodies are markers of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -79.323 |
| Week 52 vs. Week 16 | -48.175 |
Isoleucine is a marker of adipose dysfunction and general metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | µmol/L (Mean) |
|---|---|
| Week 52 vs. Baseline | -3.541 |
| Week 52 vs. Week 16 | 5.203 |
Insulin is a marker of glucose metabolism. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 421.436 |
| Week 52 vs. Week 16 | 330.523 |
IL2RA is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | ng/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -1.557 |
| Week 52 vs. Week 16 | 0.782 |
IL-9 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | -0.025 |
| Week 52 vs. Week 16 | 0.080 |
IL-8 is a marker of inflammation. (NCT03082729)
Timeframe: After the completion of week 52 visit by all study participants.
| Intervention | pg/ml (Mean) |
|---|---|
| Week 52 vs. Baseline | 369.437 |
| Week 52 vs. Week 16 | 330.646 |
"The Whole Body Itch NRS scale is a 11-point scale to assess whole body itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch, and a 4-point change from baseline was shown to be optimal for demonstrating a level of clinically meaningful improvement in itch severity." (NCT03123471)
Timeframe: Baseline to Weeks 2, 4, 6, 8 and 12
| Intervention | Percentage of Participants (Number) | |||
|---|---|---|---|---|
| Week 2 | Week 4 | Week 8 | Week 12 | |
| Apremilast | 20.5 | 32.3 | 39.8 | 47.0 |
| Placebo/Apremilast | 3.5 | 10.1 | 19.7 | 26.3 |
"The scalp itch NRS is a 11-point scale to assess scalp itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch." (NCT03123471)
Timeframe: Baseline to Weeks 2, 4, 8 and 12
| Intervention | Percentage of Participants (Number) | |||
|---|---|---|---|---|
| Week 2 | Week 4 | Week 8 | Week 12 | |
| Apremilast | 26.1 | 37.8 | 45.6 | 46.5 |
| Placebo/Apremilast | 11.5 | 16.5 | 23.7 | 19.6 |
A TEAE is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes above. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = could be non-serious or serious) = symptoms causing severe pain discomfort. (NCT03123471)
Timeframe: Weeks 16 to Week 32; the mean treatment duration was 14.6 weeks and 15.3 weeks in the APR 30/APR 30 BID and placebo/APR 30 BID arms, respectively
| Intervention | Participants (Count of Participants) | ||||||
|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Deaths | |
| Apremilast | 66 | 17 | 4 | 5 | 4 | 4 | 0 |
| Placebo/Apremilast | 35 | 17 | 2 | 1 | 2 | 1 | 0 |
The apremilast-exposure period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. A TEAE is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes above. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = could be non-serious or serious) = symptoms causing severe pain discomfort. (NCT03123471)
Timeframe: Week 0 to 32;
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any Serious TEAE Drug Related TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | Deaths | |
| Apremilast | 144 | 103 | 8 | 6 | 3 | 13 | 15 | 0 |
| Placebo/Apremilast | 35 | 17 | 2 | 1 | 0 | 2 | 1 | 0 |
A TEAE is an AE with a start date on or after the date of the first dose of study drug and no later than 28 days after the last dose of study drug. A serious AE (SAE) is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize or may require intervention to prevent one of the outcomes above. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = could be non-serious or serious) = symptoms causing severe pain discomfort. (NCT03123471)
Timeframe: Week 0 to Week 16; mean duration of exposure was 14.5 weeks and 14.6 weeks for participants randomized to placebo and apremilast respectively.
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Any TEAE | Any Drug-related TEAE | Any Severe TEAE | Any Serious TEAE | Any TEAE Leading to Drug Interruption | Any TEAE Leading to Drug Withdrawal | |
| Apremilast | 135 | 99 | 5 | 2 | 9 | 11 |
| Placebo/Apremilast | 52 | 22 | 2 | 1 | 4 | 3 |
The ScPGA is a measurement of overall scalp involvement by the investigator at the time of evaluation. The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, scaling, and plaque elevation. When making the assessment of overall scalp severity, the investigator factored in areas that had already been cleared (ie, had scores of 0), not limited to the evaluation of remaining lesions for severity; consequently, the severity of each sign was averaged across all areas of involvement, including cleared lesions. (NCT03123471)
Timeframe: Baseline to Week 16
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo/Apremilast | 13.7 |
| Apremilast | 43.3 |
"The Whole Body Itch NRS scale is an 11-point scale to assess whole body itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch, and a 4-point change from baseline was shown to be optimal for demonstrating a level of clinically meaningful improvement in itch severity. NRS response was defined as a ≥ 4-point reduction (improvement) from baseline." (NCT03123471)
Timeframe: Baseline to Week 16
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo/Apremilast | 22.5 |
| Apremilast | 45.5 |
"The scalp itch NRS is a 11-point scale to assess scalp itch. The scale ranges from 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch." (NCT03123471)
Timeframe: Baseline to Week 16
| Intervention | Percentage of Participants (Number) |
|---|---|
| Placebo/Apremilast | 21.1 |
| Apremilast | 47.1 |
"DLQI is questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from Very Much (score 3) to Not at All or Not relevant (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if No, then the subject is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being A lot, A little, or Not at all (scores 2, 1, or 0 respectively). The DLQI total score was derived by summing all item scores, and has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best." (NCT03123471)
Timeframe: Baseline to Week 16
| Intervention | Units on a Scale (Least Squares Mean) |
|---|---|
| Placebo/Apremilast | -3.8 |
| Apremilast | -6.7 |
"Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcoholic drinks consumed per day with a minimum value of 0 and an undetermined maximum value.~Treatment effects on drinking were accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing." (NCT03175549)
Timeframe: 11 days (Treatment effects on drinking were accessed during the 11 days of ad libidum and did not include the final three days of mandatory abstinence prior to cue reactivity testing on day 14 of dosing.)
| Intervention | Drinks per day (Mean) |
|---|---|
| Apremilast (Otezla) | 3.71 |
| Placebo | 3.92 |
Total Visual Analog Scale (VAS) scores of craving severity in response to in vivo alcohol cues. Higher scores indicate greater craving severity with a minimum score of 0 and a maximum score of 80. (NCT03175549)
Timeframe: 1 hour on the last day of dosing (Day 14)
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast (Otezla) | 33.84 |
| Placebo | 28.31 |
Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18. (NCT03239106)
Timeframe: Screening through Week 18 (follow up visit)
| Intervention | Dermatology Life Quality Index Score (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Screening | Baseline (Week 0) | Week 2 | Week 4 | Week 8 | Week 12 | Week 16 | Week 18 | |
| Open Label | 15.3 | 13.7 | 13.3 | 10.8 | 7.5 | 4.7 | 2.3 | 5.0 |
"Participants will complete a Numeric Rating Scale for itch (0 representing no itching through 10 representing worst itch imaginable) will be recalled from prior 24 hours and the prior week.~0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10." (NCT03239106)
Timeframe: Week 16
| Intervention | Units on a scale (Median) | |
|---|---|---|
| 24 Hour NRS Itch Score | 1 Week NRS Itch Score | |
| Open Label | 7 | 7.5 |
"Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16~The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score)." (NCT03239106)
Timeframe: Week 16
| Intervention | Score on a scale (Median) |
|---|---|
| Open Label | 13 |
"Participants' itch will be measured utilizing the Numeric Rating Scale for itch (0 representing no itching through 10 representing worst itch imaginable) will be recalled from prior 24 hours and the prior week.~0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10." (NCT03239106)
Timeframe: Screening through Week 18 (follow up visit)
| Intervention | Numerical Rating Scale Itch Score (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Screening | Baseline (Week 0) | Week 2 | Week 4 | Week 8 | Week 12 | Week 16 | Week 18 | |
| Open Label | 8.9 | 7.9 | 5.7 | 6.5 | 7.0 | 5.7 | 3.0 | 1.0 |
To assess change in serum myeloperoxidase in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed (NCT03442088)
Timeframe: Baseline, Week 16
| Intervention | Pg/mL (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast for Treatment of Psoriasis With the AM-endotype | 24198 | 24294 |
To assess change in IL-17 in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed (NCT03442088)
Timeframe: Baseline, Week 16
| Intervention | Pg/mL (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast for Treatment of Psoriasis With the AM-endotype | 1.513 | -0.8315 |
To assess change in Tissue Factor in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed (NCT03442088)
Timeframe: Baseline, Week 16
| Intervention | Pg/mL (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast for Treatment of Psoriasis With the AM-endotype | 72.28 | 75.52 |
To assess change in in the identified patient AM-endotype computing relative percent reduction for each subject being treated and serum marker. The median and other summary statistics of these percent change values will be computed (NCT03442088)
Timeframe: Baseline, Week 16
| Intervention | Pg/mL (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast for Treatment of Psoriasis With the AM-endotype | 14.95 | 14.26 |
For each subject, we will identify a target biomarker of abnormally elevated monocytes, among 1.) intermediate, or 2.) doublets, or 3.) platelet doubles. Each subject will thus have one identified monocyte biomarker for which relative percent change will be its basis for analysis in the primary outcome measure. We will specifically assess change from baseline to 16 weeks by computing relative percent reduction for each subject being treated. Note for example that a change of 1.5% to 1.2% is (1 - (1.2/1.5))*100% = 20% reduction. The median and other summary statistics of these percent change values will be computed. Wilcoxon's signed rank test will be used to evaluate the null hypothesis of the median percent change being 0. (NCT03442088)
Timeframe: Baseline, Week 16
| Intervention | Percent change (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast for Treatment of Psoriasis With the AM-endotype | 0.5665 | 0.1715 |
Mean change in IGSS at Week 24 compared to Baseline. Treatment response will be considered no change or improvement in IGSS. CCCA Investigator Global Severity Score (IGSS) assess subjects on a scale of 0 (no hair loss) to 6 (severe CCCA, e.g. >75% involvement of vertex). (NCT03521687)
Timeframe: Week 0 and Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | -0.31 |
Mean change in DLQI total score at Week 24 as compared to Baseline. DLQi is a 10-item questionnaire, each question is scored from 0 to 3, giving a possible score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). (NCT03521687)
Timeframe: Week 0 and Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | -2.18 |
Change in NRS at Week 24 as compared to Baseline. Subjects will complete a symptom severity questionnaire consisting of 3 numeric rating scales (NRS) measuring severity of pruritus, burning, and pain. The NRS will range from 0 (no symptoms) to 10 (severe symptoms). Patients indicate the intensity of each symptom (pruritus, burning, or pain) by choosing a number from 0 to 10 that corresponds to the severity of that symptom. (NCT03521687)
Timeframe: Week 0 and Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | 0.94 |
Mean change in PGA-I at Week 24 compared to Baseline. Trained study personnel will take standardized photographs of the scalp. These photographs will be provided to a panel of three dermatologists with expertise in CCCA, each of whom will review the photographs at these time points. Investigators will assess the improvement in hair loss severity using PGA-I. PGA-I will range from -3 (significant worsening) to 3 (significant improvement). (NCT03521687)
Timeframe: Week 0 and Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | 0.07 |
"Mean change in VAS at Week 24 compared to Baseline. The VAS is a numerical scale used to assess patients' perception of hair loss severity. The evaluation is a 10cm long line on which the subjects indicate the severity of their condition from 0 (complete loss of hair in affected area - ie no visible hairs on central scalp) to 10 (full growth/regrowth in affected area-ie no visible hair loss on central scalp)." (NCT03521687)
Timeframe: Week 0 and Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | -1.94 |
Mean change in PaGA-I at Week 24 as compared to Baseline. PaGA-I will range from -3 (significant worsening) to 3 (significant improvement). (NCT03521687)
Timeframe: Week 0 and Week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | 1 |
Mean change in CHLG at Week 24 compared to Baseline. Degree of severity of hair loss is graded on a 6-point visual scale (pattern 0: no hair loss, pattern 1-2: mild hair loss, pattern 3-5: more severe hair loss). (NCT03521687)
Timeframe: Week 0 and week 24
| Intervention | score on a scale (Mean) |
|---|---|
| Apremilast | -0.44 |
Skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment to assess changes in gene expression profiling and immunohistochemistry stain. Gene expression profiling will be analyzed using inferential statistics with a False Discovery Rate (FDR) of < 0.05. (NCT03529955)
Timeframe: Data collected at 3 months after baseline visit
| Intervention | Change (Number) | |
|---|---|---|
| Down regulated genes | Up regulated genes | |
| Skin Biopsy at 3 Months Into Apremilast Therapy for Gene Expression Profiling | 123 | 72 |
| Skin Biopsy at Baseline for Gene Expression Profiling | 0 | 0 |
Skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment to assess changes in immunohistochemistry stain. (NCT03529955)
Timeframe: Data collected at 3 months after baseline visit
| Intervention | Percentage of positive cell detection (Mean) | |
|---|---|---|
| STAT1 | STAT3 | |
| Skin Biopsy at 3 Months Into Apremilast Therapy for IHC | 50.1 | 17.4 |
| Skin Biopsy at Baseline for IHC | 96.2 | 44.3 |
"Cutaneous dermatomyositis disease area and severity index (CDASI) activity score is a validated tool to measure skin disease activity in dermatomyositis. The overall response rate (ORR) includes partial and complete responses. Complete response is defined by a CDASI activity score of zero. Partial response is defined by a decrease of CDASI activity score of at least 4 points. Calculation is performed as the CDASI activity score at 3 month(s) minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF).~CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome." (NCT03529955)
Timeframe: Data collected at 3 months after baseline visit
| Intervention | Participants (Count of Participants) |
|---|---|
| Dermatomyositis Patients With Refractory Cutaneous Disease | 7 |
"MMT-8 (Manual Muscle Testing-8) score is a validated tool to assess muscle strength. Calculate the mean change in MMT-8 score at 3 and 6 month(s) compared to baseline in patients with muscle disease.~Units: Units on a scale. Scale goes from 0-150. 150 is perfect strength." (NCT03529955)
Timeframe: Data collected at 3 and 6 months after baseline visit
| Intervention | score on a scale (Mean) |
|---|---|
| MMT-8 Score at 3 Months | 143.3 |
| MMT-8 Score at 6 Months | 144.5 |
"Dermatology Life Quality Index (DLQI) is a validated tool to measure quality of life in patients with skin disease. Complete response is defined by a DLQI of zero at 3, and 6 months. Partial response is defined by a decrease of DLQI of at least 5 points at 3, and 6 months compared to baseline. Calculation is performed as the DLQI at 3, and 6 months minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF).~Units : Units on a scale from 0-30, higher scores represent worse outcome." (NCT03529955)
Timeframe: Data collected at 3 and 6 months after baseline visit
| Intervention | score on a scale (Mean) |
|---|---|
| DLQI Score at 3 Months | 6.3 |
| DLQI Score at 6 Months | 4.2 |
"The durability of response will be measured using the CDASI activity score at 6 months minus CDASI activity score at 3 months. Complete response durability is defined as zero or minus difference between CDASI activity score at 6 months and CDASI activity score at 3 months. Partial response durability is defined as >4 points difference between CDASI activity score at 6 months and CDASI activity score at 3 months. Missing data will be handled using the last observation carried forward approach (LOCF).~CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome." (NCT03529955)
Timeframe: Data collected at 6 months compared to data collected at 3 months
| Intervention | score on a scale (Mean) |
|---|---|
| CDASI Score at 3 Months | 16.9 |
| CDASI Score at 6 Months | 14 |
"The proportion of participants experiencing adverse events and serious adverse events was measured over 7 months period (6 months during the study and 1 month follow up) using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.~Grade refers to severity of the AE. The CTCAE displays Grades 1 to 5 with unique clinical descriptions of severity for each AE:~Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age- appropriate instrumental Activity of Daily Living (ADL) Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE All adverse events subjects experienced were grade 1 or 2 which is mild to moderate in severity." (NCT03529955)
Timeframe: 7 months
| Intervention | Participants (Count of Participants) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Headache Grade 1-2 | Nausea Grade 1-2 | Diarrhea Grade 1-2 | Herpes Zoster Grade 1-2 | Influenza Grade 1-2 | Pneumonia Grade 1-2 | Acute sinusitis Grade 1-2 | Hypertension Grade 1-2 | Ocular pressure Grade 1-2 | |
| Dermatomyositis Patients With Refractory Cutaneous Disease | 7 | 5 | 4 | 2 | 1 | 1 | 1 | 1 | 1 |
"Relapse is defined as 50% loss or greater of Week 24 PASI percent improvement from baseline.~The PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity." (NCT03611751)
Timeframe: From Week 24 to Week 52 (up to approximately 28 weeks)
| Intervention | Days (Median) |
|---|---|
| BMS-986165 | NA |
| Placebo | NA |
| Apremilast | 197.0 |
"The Psoriasis Area and Severity Index (PASI) is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.~PASI is a measure of the average erythema (redness), infiltration (thickness), and desquamation (scaling) of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 90 is the response as a number of participants who experience at least a 90% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method. Baseline is defined as the measurement at the randomization visit (Week 0).~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 24 or who have missing Week 24 endpoint data for any reason." (NCT03611751)
Timeframe: Baseline and week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 164 |
| Apremilast | 50 |
"The Psoriasis Area and Severity Index (PASI) is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.~The PASI is a measure of the average erythema (redness), infiltration (thickness), and desquamation (scaling) of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method. Baseline is defined as the measurement at the randomization visit (Week 0).~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 271 |
| Apremilast | 101 |
"PSSD assesses the severity of 5 symptoms (itch, pain, stinging, burning, skin tightness) and 6 participant-observed signs (skin dryness, cracking, scaling, shedding or flaking, redness, bleeding). The severity of each item is rated on an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Both symptom and sign scores are derived by averaging the questions and multiplying by 10. A total PSSD score ranging 0-100 will be derived from taking the average of the symptom and sign scores. 0 represents the least severe symptom/sign and 100 represents the most severe. Baseline is defined as the measurement at the randomization visit (Week 0).~A modified observation carried forward (mBOCF) approach will be used for missing data. The baseline observation will be carried forward for participants who discontinue study treatment for all analysis weeks after the assessment time point of discontinuation due to lack of efficacy and AEs." (NCT03611751)
Timeframe: Baseline and Week 16
| Intervention | Score on a scale (Mean) |
|---|---|
| BMS-986165 | -28.9 |
| Placebo | -4.2 |
| Apremilast | -21.5 |
"The sPGA is a 5-point scale average assessment of all psoriatic lesions graded for erythema, scale, and induration. The sPGA measure determines psoriasis severity at a single point in time (without taking into account the baseline disease condition) as: clear (0), almost clear (1), mild (2), moderate (3), or severe (4). The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity. sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 or 1 with at least a 2-point improvement from baseline using the non-responder imputation (NRI) method.~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 253 |
| Placebo | 22 |
Psoriasis Symptoms and Signs Diary (PSSD) is an 11-item participant-reported instrument that assesses severity of symptoms and participant-observed signs commonly associated in plaque psoriasis. The PSSD assesses severity of 5 symptoms (itch, pain, stinging, burning, skin tightness) and 6 participant-observed signs (skin dryness, cracking, scaling, shedding or flaking, redness, bleeding) using 0 to 10 numerical ratings. The severity of each item is rated on an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable) where the symptoms summary score is derived from the average of the scores. A higher score indicates more severe disease. PSSD 0 is the response as a number of participants who experience a PSSD symptom score that determines psoriasis severity as 0 among participants with a baseline PSSD symptom score >= 1 using the non-responder imputation (NRI) method. (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 35 |
| Placebo | 3 |
| Apremilast | 10 |
"The Psoriasis Area and Severity Index (PASI) is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.~The PASI is a measure of the average erythema (redness), infiltration (thickness), and desquamation (scaling) of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 100 is the response as a number of participants who experience at least a 100% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method. Baseline is defined as the measurement at the randomization visit (Week 0).~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 52 |
| Placebo | 3 |
| Apremilast | 11 |
"The Psoriasis Area and Severity Index (PASI) is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.~PASI is a measure of the average erythema (redness), infiltration (thickness), and desquamation (scaling) of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method. Baseline is defined as the measurement at the randomization visit (Week 0).~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 24 or who have missing Week 24 endpoint data for any reason." (NCT03611751)
Timeframe: Baseline and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 296 |
| Apremilast | 96 |
"The sPGA is a 5-point scale average assessment of all psoriatic lesions graded for erythema, scale, and induration. The sPGA measure determines psoriasis severity at a single point in time (without taking into account the baseline disease condition) as: clear (0), almost clear (1), mild (2), moderate (3), or severe (4). The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. sPGA 0 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 using the non-responder imputation (NRI) method.~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 80 |
| Placebo | 3 |
| Apremilast | 16 |
"The sPGA is a 5-point scale average assessment of all psoriatic lesions graded for erythema, scale, and induration. The sPGA measure determines psoriasis severity at a single point in time (without taking into account the baseline disease condition) as: clear (0), almost clear (1), mild (2), moderate (3), or severe (4). The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. sPGA 0/1 is the number of participants with a sPGA score of 0 or 1 with at least a 2-point improvement from baseline.~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 253 |
| Apremilast | 86 |
"The Psoriasis Area and Severity Index (PASI) is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.~The PASI is a measure of the average erythema (redness), infiltration (thickness), and desquamation (scaling) of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method. Baseline is defined as the measurement at the randomization visit (Week 0).~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 271 |
| Placebo | 24 |
"The Psoriasis Area and Severity Index (PASI) is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance.~The PASI is a measure of the average erythema (redness), infiltration (thickness), and desquamation (scaling) of psoriatic skin lesions (each graded on a 0-4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 90 is the response as a number of participants who experience at least a 90% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method. Baseline is defined as the measurement at the randomization visit (Week 0).~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 138 |
| Placebo | 7 |
| Apremilast | 46 |
"The DLQI is a participant-reported quality of life index which consists of 10 questions concerning how much skin problems affect symptoms and feelings, daily activities, leisure, work, school, personal relationships, and treatment during the last week. Each question is scored on a scale of 0 to 3 where 0 = not at all, 1 =a little, 2 = a lot, or 3 = very much. The scores are summed, giving a range from 0 (no impairment of life quality) to 30 (maximum impairment). DLQI 0/1 is the number of participants with a score of 0 or 1 among participants with a baseline DLQI score ≥2.~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 186 |
| Placebo | 24 |
The palmoplantar Physician's Global Assessment (pp-PGA) score evaluates palmoplantar (including finger and toe surfaces) psoriasis lesions based on overall severity by investigator, then scored on the following 5-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; and 4 = severe. pp-PGA 0/1 is the number of participants with a score of 0 or 1 among participants with a baseline pp-PGA score ≥ 3. (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 18 |
| Placebo | 4 |
| Apremilast | 8 |
"The Physician Global Assessment- Fingernails (PGA-F) evaluates the overall condition of the fingernails and is rated on a 5-point scale:0 = clear, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe. PGA-F 0/1 is the response as a number of participants with a PGA-F score of 0 or 1 with at least a 2-point improvement from baseline among participants with a baseline PGA-F score >=3.~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 14 |
| Placebo | 3 |
"The scalp specific Physician's Global Assessment (ss-PGA) evaluates scalp lesions in terms of clinical signs of redness, thickness, and scaliness and scored on the following 5-point ss-PGA scale: 0 = absence of disease, 1 = very mild disease, 2 = mild disease, 3 = moderate disease, 4 = severe disease. ss-PGA 0/1 is the response as a number of participants who experience a ss-PGA score of 0 or 1 with at least a 2-point improvement from baseline among participants with a baseline ss-PGA score ≥3 .~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 16 or who have missing Week 16 endpoint data for any reason." (NCT03611751)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 182 |
| Placebo | 30 |
| Apremilast | 61 |
"The sPGA is a 5-point scale average assessment of all psoriatic lesions graded for erythema, scale, and induration. The sPGA measure determines psoriasis severity at a single point in time (without taking into account the baseline disease condition) as: clear (0), almost clear (1), mild (2), moderate (3), or severe (4). The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. sPGA 0/1 is the number of participants with a sPGA score of 0 or 1.~Non-responder imputation (NRI) will be used for participants who: Discontinue treatment or study prior to Week 24 or who have missing Week 24 endpoint data for any reason." (NCT03611751)
Timeframe: Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 251 |
| Apremilast | 75 |
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; 4 = Severe). sPGA 0 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason. (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 58 |
| Placebo | 1 |
| Apremilast | 8 |
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; Severe = 4). sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 or 1 with at least 2-point improvement from baseline using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason. (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 178 |
| Placebo | 12 |
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; Severe = 4). sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 or 1 with at least 2-point improvement from baseline using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 52 or who have missing week 52 endpoint data for any reason. (NCT03624127)
Timeframe: Week 52 and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 151 |
| Apremilast | 37 |
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; Severe = 4). sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 or 1 with at least 2-point improvement from baseline using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 24 or who have missing week 24 endpoint data for any reason. (NCT03624127)
Timeframe: Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 195 |
| Apremilast | 52 |
The sPGA is a 5-point scale of an average assessment of all psoriatic lesions based on erythema, scale, and induration. The average of the 3 scales, which is rounded to the nearest whole number, is the final sPGA score. The higher sPGA score denotes to more severe disease activity (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; Severe = 4). sPGA 0/1 is the response as a number of participants who experience a sPGA score that determines psoriasis severity as 0 or 1 with at least 2-point improvement from baseline using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason. (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 178 |
| Apremilast | 54 |
ss-PGA is a 5-point scale that evaluates scalp lesions in terms of clinical signs of redness, thickness, and scaliness. The higher ss-PGA score denotes to more severe disease activity (0 = absence of disease; 1 = very mild disease; 2 = mild disease; 3 = moderate disease; 4 = severe disease). ss-PGA 0/1 is the response as a number of participants who experience a ss-PGA score that determines scalp lesions severity as 0 or 1 with at least a 2-point improvement from baseline among participants with a baseline ss-PGA score >=3. (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 147 |
| Placebo | 21 |
| Apremilast | 43 |
"DLQI is a participant-reported quality of life index which consists of 10 questions concerning symptoms and feelings, daily activities, leisure, work, school, personal relationships, and treatment during the last week before questionnaire. Each question is scored on a scale of 0 to 3 by a tick box (0 = not at all; 1 = a little; 2 = a lot; or 3 = very much). The scores are summed, giving a range from 0 (no impairment of life quality) to 30 (maximum impairment). DLQI 0/1 is the response as a number of participants who experience DLQI score of 0 or 1 among participants with a baseline DLQI score >=2." (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 132 |
| Placebo | 17 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 90 is the response as a number of participants who experience at least a 90% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 52, or who have missing week 52 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline, Week 52 and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 103 |
| Apremilast | 26 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 90 is the response as a number of participants who experience at least a 90% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 24 or who have missing week 24 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 140 |
| Apremilast | 37 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 100 is the response as a number of participants who experience at least a 100% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 47 |
| Placebo | 1 |
PSSD with a 24-hour recall period is an 11-item participant-reported instrument that assesses severity of symptoms and participant-observed signs commonly associated in plaque psoriasis. PSSD assesses severity of 5 symptoms (itch, pain, stinging, burning, skin tightness) and 6 participants-observed signs (skin dryness, cracking, scaling, shedding or flaking, redness, bleeding) using 0-10 numerical ratings. The severity of each item is rated on an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). PSSD 0 is the response as a number of participants who experience a PSSD symptom score that is derived from the average of the scores and determines psoriasis severity as 0 among participants with a baseline PSSD symptom score >= 1. (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 24 |
| Placebo | 1 |
| Apremilast | 7 |
PGA-F overall condition of the fingernails is rated on a 5-point scale (0 = clear; 1 = minimal; 2 = mild; 3 = moderate; and 4 = severe). PGA-F 0/1 is the response as a number of participants with a PGA-F score of 0 or 1 with at least a 2-point improvement from baseline among participants with a baseline PGA-F score >=3. (NCT03624127)
Timeframe: Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 9 |
| Placebo | 3 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 90 is the response as a number of participants who experience at least a 90% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 118 |
| Placebo | 7 |
| Apremilast | 33 |
"PSSD is an 11-item participant-reported instrument that assesses severity of symptoms and participant-observed signs commonly associated in plaque psoriasis. PSSD assesses severity of 5 symptoms (itch, pain, stinging, burning, skin tightness) and 6 participants-observed signs (skin dryness, cracking, scaling, shedding or flaking, redness, bleeding) using 0-10 numerical ratings. The severity of each item is rated on an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). A symptom score will be derived by averaging the 5 questions and multiplying by 10. A sign score will be derived by averaging the 6 questions and multiplying by 10. A total PSSD score with range 0-100 will be derived from taking the average of the symptom and sign scores, where 0 representing the least severe symptom/sign and 100 the most severe. A mBOCF approach will be used for missing data.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 16
| Intervention | Score on a scale (Mean) |
|---|---|
| BMS-986165 | -29.4 |
| Apremilast | -22.8 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 52, or who have missing week 52 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline, Week 52 and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 187 |
| Apremilast | 51 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 24 or who have missing week 24 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 24
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 230 |
| Apremilast | 64 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 194 |
| Placebo | 21 |
"PASI is a measure of the average redness, thickness, and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. PASI 75 is the response as a number of participants who experience at least a 75% improvement in PASI score as compared with the baseline value using the non-responder imputation (NRI) method that will be used for participants who discontinue treatment or study prior to week 16 or who have missing week 16 endpoint data for any reason.~Baseline is defined as the measurement at the randomization visit (Week 0)." (NCT03624127)
Timeframe: Baseline and Week 16
| Intervention | Participants (Count of Participants) |
|---|---|
| BMS-986165 | 194 |
| Apremilast | 59 |
The length of time of remission of RAS lesions experienced by the subjects. As measured in months. (NCT03690544)
Timeframe: 24 weeks
| Intervention | months (Mean) |
|---|---|
| Single Arm | 2.00 |
The total length of time (duration) subjects experienced RAS lesions. Measured in weeks (NCT03690544)
Timeframe: 24 weeks
| Intervention | weeks (Mean) |
|---|---|
| Single Arm | 1.57 |
Number of subjects who prematurely discontinue treatment with apremilast due to any adverse event. (NCT03690544)
Timeframe: 24 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Single Arm | 3 |
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (NCT03690544)
Timeframe: 24 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Single Arm | 11 |
Number of participants with fewer oral ulcers at Week 24 compared to Baseline (NCT03690544)
Timeframe: baseline, 24 weeks
| Intervention | participants (Number) |
|---|---|
| Single Arm | 11 |
"The Visual Analog Scale (VAS) for Pain is a validated tool used to measure pain. A 100mm horizontal line anchored by no pain (score of 0) and pain as bad as it could be (score of 100)." (NCT03690544)
Timeframe: baseline, 16 weeks, 24 weeks
| Intervention | units on a scale (Mean) | |
|---|---|---|
| baseline to 16 weeks | baseline to 24 weeks | |
| Single Arm | -4 | -2 |
The participants' BMI was calculated as body weight (kg)/height (m^2). (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | kg/m^2 (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast | 21.33 | 20.98 |
| Placebo | 21.41 | 21.87 |
The participants' BMI was calculated as body weight (kg)/height (m^2). (NCT03701763)
Timeframe: Baseline and Week 52
| Intervention | kg/m^2 (Mean) | |
|---|---|---|
| Baseline | Week 52 | |
| Apremilast Exposure Period: Apremilast 20 mg BID | 18.32 | 18.30 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 24.52 | 23.95 |
The sPGA is the assessment by the Investigator of the overall disease severity of plaque psoriasis at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. The results presented are for the percentage of participants with a sPGA response. An sPGA response was defined as a score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline at Week 16. (NCT03701763)
Timeframe: Baseline to Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 11.5 |
| Apremilast | 33.1 |
The Psoriasis Area Severity Index (PASI) is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The results presented are for the percentage of participants with PASI-75. PASI-75 was defined as at least a 75% reduction in PASI score from baseline. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 16.1 |
| Apremilast | 45.4 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The results presented are for the percentage of participants with PASI-50. PASI-50 was defined as at least a 50% reduction in PASI score from baseline. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 32.1 |
| Apremilast | 70.5 |
The CDLQI is designed to measure the impact of skin disease on children's quality of life. The CDLQI measures how much the participant's psoriasis has affected them over the last week, and includes 10 questions with possible answers ranging from not at all (score of 0) to very much (score of 3). The CDLQI total score ranged from 0 (no effect on the participant's life) to 30 (extremely large effect on the participant's life). The results presented are for the percentage of participants who achieved a total CDLQI score of 0 or 1 at Week 16. (NCT03701763)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 31.3 |
| Apremilast | 35.4 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Positive percentage change from baseline scores indicate a worsening of disease severity, and negative percentage change from baseline scores indicate an improvement in disease severity. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | percentage change (Mean) |
|---|---|
| Placebo | -37.49 |
| Apremilast | -64.52 |
BSA is a measurement of involved skin of the whole body affected by psoriasis, which ranges from 0% to 100%. Positive percentage change from baseline indicates that a greater BSA was affected by psoriasis. A negative percentage change from baseline indicates that a lesser BSA was affected by psoriasis. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | percentage change in affected BSA (Mean) |
|---|---|
| Placebo | -20.56 |
| Apremilast | -55.44 |
The C-SSRS is a questionnaire that is used to assess suicidal ideation and behavior. The C-SSRS questionnaire measures suicidal ideation, intensity of ideation, and suicidal behaviors. Results presented are for the number of participants who recorded suicidal ideation or behavior on the C-SSRS. (NCT03701763)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 0 |
| Apremilast | 0 |
The C-SSRS is a questionnaire that is used to assess suicidal ideation and behavior. The C-SSRS questionnaire measures suicidal ideation, intensity of ideation, and suicidal behaviors. Results presented are for the number of participants who recorded suicidal ideation or behavior on the C-SSRS. (NCT03701763)
Timeframe: Week 16 to Week 52
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast-extension Phase: Apremilast 20 mg BID | 0 |
| Apremilast-extension Phase: Apremilast 30 mg BID | 0 |
A TREAE is any AE that is determined by the Investigator to have a possibly causal relationship to the investigational product. (NCT03701763)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 12 |
| Apremilast 20mg | 36 |
| Apremilast 30 mg | 32 |
A TESAE is any AE occurring at any dose after first dose that results in death, is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE), requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay), results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions), is a congenital anomaly/birth defect, or constitutes an important medical event. (NCT03701763)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 1 |
| Apremilast 20mg | 2 |
| Apremilast 30 mg | 0 |
An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of the study. A TEAE is any AE that occurred after first dose of the investigational product. (NCT03701763)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 33 |
| Apremilast 20mg | 58 |
| Apremilast 30 mg | 48 |
A TREAE is any AE that is determined by the Investigator to have a possibly causal relationship to the investigational product. (NCT03701763)
Timeframe: 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast Exposure Period: Apremilast 20 mg BID | 45 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 47 |
A TESAE is any AE occurring at any dose after first dose that results in death, is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE), requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay), results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions), is a congenital anomaly/birth defect, or constitutes an important medical event. (NCT03701763)
Timeframe: 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast Exposure Period: Apremilast 20 mg BID | 2 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 1 |
An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of the study. A TEAE is any AE that occurred after first dose of the investigational product. (NCT03701763)
Timeframe: 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast Exposure Period: Apremilast 20 mg BID | 88 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 80 |
A psoriasis flare was defined as a sudden intensification of psoriasis (new generalized erythrodermic, inflammatory or pustular psoriasis) requiring medical intervention beyond allowable medications. (NCT03701763)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 3 |
| Apremilast | 2 |
A psoriasis flare was defined as a sudden intensification of psoriasis (new generalized erythrodermic, inflammatory or pustular psoriasis) requiring medical intervention beyond allowable medications. (NCT03701763)
Timeframe: 52 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Apremilast Exposure Period: Apremilast 20 mg BID | 7 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 11 |
The CDLQI is designed to measure the impact of skin disease on children's quality of life. The CDLQI measures how much the participant's psoriasis has affected them over the last week, and includes 10 questions with possible answers ranging from not at all (score of 0) to very much (score of 3). The CDLQI total score ranged from 0 (no effect on the participant's life) to 30 (extremely large effect on the participant's life). A positive change from baseline score indicates that a participant's quality of life has worsened. A negative change from baseline score indicates that a participant's quality of life has improved. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | scores on a scale (Mean) |
|---|---|
| Placebo | -2.7 |
| Apremilast | -5.3 |
A psoriasis rebound was defined as an adverse event of psoriasis that started after the last dose date for participants who received treatment in the study. (NCT03701763)
Timeframe: 14 weeks post last dose (max mean treatment duration in placebo-controlled phase was 15.3 weeks, and 41.9 weeks in the apremilast-exposure period)
| Intervention | Participants (Count of Participants) |
|---|---|
| Placebo | 0 |
| Apremilast 20 mg BID | 0 |
| Apremilast 30 mg BID | 4 |
Diarrhea symptoms were nausea, vomiting, abdominal cramps, abdominal pain, fever, bloating, and other symptoms. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms. (NCT03701763)
Timeframe: Up to approximately 113 days
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1 to 2872563612 | Day 1 to 2872563613 | Day 29 to 5672563612 | Day 29 to 5672563613 | Day 57 to 8472563612 | Day 57 to 8472563613 | Day 85 to 11272563612 | Day 85 to 11272563613 | Day >/= 11372563612 | Day >/= 11372563613 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nausea | Vomiting | Abdominal cramps | Abdominal pain | Fever | Bloating | Other symptoms | No symptoms | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 32 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 16 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 28 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 21 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 53 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 33 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 17 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 56 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 81 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 65 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 103 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 66 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 125 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 79 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 154 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diarrhea symptoms were nausea, vomiting, abdominal cramps, abdominal pain, fever, bloating, and other symptoms. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms. (NCT03701763)
Timeframe: Day 1 up to approximately 365 days
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1 to 2872563616 | Day 1 to 2872563617 | Day 29 to 5672563616 | Day 29 to 5672563617 | Day 57 to 8472563617 | Day 57 to 8472563616 | Day 85 to 11272563616 | Day 85 to 11272563617 | Day 113 to 14072563616 | Day 113 to 14072563617 | Day 141 to 16872563617 | Day 141 to 16872563616 | Day 169 to 19672563617 | Day 169 to 19672563616 | Day 197 to 22472563617 | Day 197 to 22472563616 | Day 225 to 25272563616 | Day 225 to 25272563617 | Day 253 to 28072563617 | Day 253 to 28072563616 | Day 281 to 30872563617 | Day 281 to 30872563616 | Day 309 to 33672563617 | Day 309 to 33672563616 | Day 337 to 36472563616 | Day 337 to 36472563617 | Day >= 36572563616 | Day >= 36572563617 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other symptoms | No symptoms | Nausea | Bloating | Vomiting | Abdominal cramps | Abdominal pain | Fever | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 17 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 21 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 21 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 38 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 43 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 70 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 59 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 76 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 76 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 86 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 68 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 95 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 79 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 87 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 72 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 97 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 64 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 92 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 55 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 58 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 49 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 47 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 57 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 52 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 30 mg BID | 54 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Exposure Period: Apremilast 20 mg BID | 24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The Tanner Staging of sexual development is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on characteristics, such as the size of the breasts, genitals, testicular volume, and growth of pubic hair. The scale ranges from stage I (pre-adolescent) to stage V (adult development). The results presented are for the number of participants at stage I-V of development. (NCT03701763)
Timeframe: Week 52
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Testes Growth72563620 | Testes Growth72563621 | Penis Growth72563621 | Penis Growth72563620 | Pubic Hair Growth72563621 | Pubic Hair Growth72563620 | Other Changes72563620 | Other Changes72563621 | |||||||||||||||||||||||||||||||||||||||||
| Stage 2 | Stage 3 | Stage 4 | Stage 5 | Missing | Stage 1 | |||||||||||||||||||||||||||||||||||||||||||
| Placebo | 11 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 5 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 4 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 12 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 27 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 5 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 11 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 10 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 14 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 28 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 10 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 15 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 6 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 8 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 6 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 14 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 13 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 26 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 9 | |||||||||||||||||||||||||||||||||||||||||||||||
| Placebo | 7 | |||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast | 9 | |||||||||||||||||||||||||||||||||||||||||||||||
The Tanner Staging of sexual development is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on characteristics, such as the size of the breasts, genitals, testicular volume, and growth of pubic hair. The scale ranges from stage I (pre-adolescent) to stage V (adult development). The results presented are for the number of participants at stage I-V of development. (NCT03701763)
Timeframe: Week 52
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Breast Growth72563620 | Breast Growth72563621 | Pubic Hair Growth72563620 | Pubic Hair Growth72563621 | Other Changes72563621 | Other Changes72563620 | |||||||||||||||||||||||||||||||
| Missing | Stage 2 | Stage 3 | Stage 4 | Stage 1 | Stage 5 | |||||||||||||||||||||||||||||||
| Apremilast | 17 | |||||||||||||||||||||||||||||||||||
| Placebo | 3 | |||||||||||||||||||||||||||||||||||
| Apremilast | 20 | |||||||||||||||||||||||||||||||||||
| Apremilast | 27 | |||||||||||||||||||||||||||||||||||
| Apremilast | 7 | |||||||||||||||||||||||||||||||||||
| Placebo | 8 | |||||||||||||||||||||||||||||||||||
| Apremilast | 9 | |||||||||||||||||||||||||||||||||||
| Placebo | 6 | |||||||||||||||||||||||||||||||||||
| Placebo | 12 | |||||||||||||||||||||||||||||||||||
| Apremilast | 28 | |||||||||||||||||||||||||||||||||||
| Placebo | 5 | |||||||||||||||||||||||||||||||||||
| Apremilast | 18 | |||||||||||||||||||||||||||||||||||
| Apremilast | 12 | |||||||||||||||||||||||||||||||||||
| Placebo | 4 | |||||||||||||||||||||||||||||||||||
| Apremilast | 16 | |||||||||||||||||||||||||||||||||||
| Apremilast | 26 | |||||||||||||||||||||||||||||||||||
| Placebo | 7 | |||||||||||||||||||||||||||||||||||
| Apremilast | 8 | |||||||||||||||||||||||||||||||||||
Diarrhea was defined as having 3 or more liquid or watery stools in a day. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms. (NCT03701763)
Timeframe: Up to approximately 113 days
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Day 1 to 28 | Day 29 to 56 | Day 57 to 84 | Day 85 to 112 | Day >/= 113 | |
| Apremilast | 67 | 51 | 41 | 29 | 9 |
| Placebo | 25 | 20 | 14 | 10 | 2 |
Diarrhea was defined as having 3 or more liquid or watery stools in a day. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms. (NCT03701763)
Timeframe: Day 1 up to approximately 365 days
| Intervention | Participants (Count of Participants) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 1 to 28 | Day 29 to 56 | Day 57 to 84 | Day 85 to 112 | Day 113 to 140 | Day 141 to 168 | Day 169 to 196 | Day 197 to 224 | Day 225 to 252 | Day 253 to 280 | Day 281 to 308 | Day 309 to 336 | Day 337 to 364 | Day >= 365 | |
| Apremilast Exposure Period: Apremilast 20 mg BID | 36 | 30 | 22 | 17 | 21 | 16 | 19 | 19 | 20 | 18 | 13 | 12 | 7 | 1 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 47 | 36 | 32 | 19 | 17 | 21 | 17 | 12 | 12 | 16 | 9 | 5 | 5 | 1 |
The participants' height in centimeters (cm) was recorded. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | cm (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast | 153.33 | 154.40 |
| Placebo | 153.29 | 154.54 |
The participants' height in centimeters (cm) was recorded. (NCT03701763)
Timeframe: Baseline and Week 52
| Intervention | cm (Mean) | |
|---|---|---|
| Baseline | Week 52 | |
| Apremilast Exposure Period: Apremilast 20 mg BID | 140.86 | 144.90 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 166.13 | 167.84 |
The participants' body weight in kilograms (kg) was recorded. (NCT03701763)
Timeframe: Baseline and Week 16
| Intervention | kg (Mean) | |
|---|---|---|
| Baseline | Week 16 | |
| Apremilast | 52.04 | 51.95 |
| Placebo | 52.36 | 54.18 |
The participants' body weight in kilograms (kg) was recorded. (NCT03701763)
Timeframe: Baseline and Week 52
| Intervention | kg (Mean) | |
|---|---|---|
| Baseline | Week 52 | |
| Apremilast Exposure Period: Apremilast 20 mg BID | 36.81 | 39.04 |
| Apremilast Exposure Period: Apremilast 30 mg BID | 67.94 | 67.79 |
"The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an Investigator's assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation of the overall scalp.~An ScPGA response is defined as and ScPGA score clear (0) or almost clear (1) with at least a 2-point reduction from baseline among participants with a baseline ScPGA score ≥ 2." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 16.6 |
| Placebo-controlled Phase: Apremilast 30 mg | 44.0 |
"The sPGA is a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 =severe. Scores incorporate an assessment by the Investigator of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation.~An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with at least a 2-point reduction from baseline at Week 16." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 4.1 |
| Placebo-controlled Phase: Apremilast 30 mg | 21.6 |
"An adverse event (AE) is An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A TEAE is any AE that occurs following administration of study treatment.~Frequency of TEAEs was assessed as well as severity and treatment relatedness.~A TEAE was considered severe based on the Investigator's assessment. A TEAE could be severe if it was serious or non-serious, had symptoms causing discomfort or pain, requiring medical or surgical attention or intervention, interfered with activities of daily life and if drug therapy was required." (NCT03721172)
Timeframe: Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up)
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| Any TEAE | Severe TEAE | Treatment-related TEAE | |
| Apremalist: Placebo-controlled Phase and Extension Phase | 351 | 24 | 186 |
| Placebo-controlled Phase: Apremilast 30 mg | 195 | 8 | 110 |
| Placebo-controlled Phase: Placebo | 139 | 2 | 36 |
The whole body itch NRS is a self-reported measure where participants were asked to assess whole body itch and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A reduction in score from baseline represents an improvement in symptoms. (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 18.6 |
| Placebo-controlled Phase: Apremilast 30 mg | 43.2 |
"The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No), and if No, then the subject is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot).~Total scores have a possible range of 0 to 30, with 30 corresponding to the worst health-related quality of life, and 0 corresponding to the best score.~A negative change from baseline indicates an improvement in health-related quality of life scores." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase: Placebo | -2.4 |
| Placebo-controlled Phase: Apremilast 30 mg | -5.2 |
"The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or handprints (each entire palmar surface or handprint equates to approximately 1% of total body surface area).~A negative change from baseline indicates a reduction of affected BSA." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage change of affected BSA (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase: Placebo | -0.07 |
| Placebo-controlled Phase: Apremilast 30 mg | -3.45 |
"The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.~PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.~A negative change from baseline indicates an improvement of disease symptoms." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase: Placebo | -0.54 |
| Placebo-controlled Phase: Apremilast 30 mg | -3.47 |
"The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or handprints (each entire palmar surface or handprint equates to approximately 1% of total body surface area)." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 22.9 |
| Placebo-controlled Phase: Apremilast 30 mg | 61.0 |
"The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or handprints (each entire palmar surface or handprint equates to approximately 1% of total body surface area)." (NCT03721172)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 7.4 |
| Placebo-controlled Phase: Apremilast 30 mg | 33.0 |
"EQ-5D measures the participants general health state as a vertical VAS and 5 quality of life domains: mobility, self-care, main activity (work, study, housework, family/leisure activities), pain/discomfort, and anxiety/depression. Each dimension is rated on three levels (no problems, some/moderate problems, extreme problems). An EQ-5D summary index is derived by applying a formula that attaches values (weights) to each of the levels in each dimension.~EQ-5D index values were derived using the UK scoring algorithm, where a higher score indicates a better health state. The range of the score is from -0.224 to 1, with 0 corresponding to death, 1 corresponding to full health, and negative numbers indicate health states worse than death. A positive change from baseline indicates improvement." (NCT03774875)
Timeframe: Baseline and week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo / Apremilast 30 mg | 214.103 |
| Apremilast 30 mg | 11.039 |
EQ-5D measures the participant's general health state on a vertical VAS and five quality of life domains. The EQ-5D VAS score ranges from 0 to 100, where a score of 0 indicates the worst imaginable health states and a score of 100 indicates the best imaginable health state. A positive change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 52
| Intervention | percent change (Mean) |
|---|---|
| Placebo / Apremilast 30 mg | 51.4 |
| Apremilast 30 mg | 33.6 |
EQ-5D measures the participant's general health state on a vertical VAS and five quality of life domains. The EQ-5D VAS score ranges from 0 to 100, where a score of 0 indicates the worst imaginable health states and a score of 100 indicates the best imaginable health state. A positive change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 18.9 |
| Apremilast 30 mg | 33.8 |
The PBI is a validated patient-reported instrument to assess patient-relevant benefits of psoriasis treatment. Prior to starting study treatment, participants were asked to assess the importance of a series of treatment goals (from not important to very important) by completing the Patient Needs Questionnaire (PNQ). After a period of treatment (16 weeks), participants were then asked to assess the extent to which these goals were achieved (from not at all to very) by completing the Patient Benefit Questionnaire (PBQ). The Patient Benefit Index represents the benefits realized as a function of most important needs. The PBI score ranges from 0 (no benefit) to 4 (maximum benefit). (NCT03774875)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 39.9 |
| Apremilast 30 mg | 76.6 |
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and the values for each anatomic region are summed to yield the PASI score. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT03774875)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 26.3 |
| Apremilast 30 mg | 39.7 |
(NCT03774875)
Timeframe: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
| Intervention | mmHg (Mean) | |
|---|---|---|
| Systolic | Diastolic | |
| Apremilast 30 mg | 0.1 | 0.1 |
(NCT03774875)
Timeframe: Baseline, week 2, week 4, and week 16
| Intervention | mmHg (Mean) | |||||
|---|---|---|---|---|---|---|
| Systolic: week 2 | Systolic: week 4 | Systolic: week 16 | Diastolic: week 2 | Diastolic: week 4 | Diastolic: week 16 | |
| Apremilast 30 mg | 0.1 | 0.4 | 1.0 | -0.6 | -1.0 | 0.6 |
| Placebo | -0.5 | 1.9 | 2.2 | -0.1 | 1.3 | 0.8 |
(NCT03774875)
Timeframe: Baseline and week 2, week 4, and week 16
| Intervention | kg (Mean) | ||
|---|---|---|---|
| Week 2 | Week 4 | Week 16 | |
| Apremilast 30 mg | -0.31 | -0.57 | -0.98 |
| Placebo | -0.02 | 0.04 | 0.08 |
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life. The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. A negative change from baseline indicates improvement in quality of life. (NCT03774875)
Timeframe: Baseline, week 32 and week 52
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | -9.9 | -11.2 |
| Placebo / Apremilast 30 mg | -9.8 | -11.3 |
"The Itch Numeric Rating Scale (NRS) asked participants to assess the worst severity of itch experienced over the past 24 hours on an 11-point scale anchored from 0, representing 'no itching' to 10, representing 'worst itch imaginable'.~A negative change from baseline indicates improvement in itch severity." (NCT03774875)
Timeframe: Baseline, week 32 and week 52
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | -2.8 | -3.3 |
| Placebo / Apremilast 30 mg | -3.2 | -3.9 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent overall work impairment takes into account both hours missed due to psoriasis symptoms and the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 52
| Intervention | percent impairment (Mean) |
|---|---|
| Placebo / Apremilast 30 mg | -21.7 |
| Apremilast 30 mg | -25.3 |
"Participants were asked to indicate their level of skin discomfort/pain in the past week by placing a vertical stroke on a 100 mm horizontal line on which the left-hand boundary (0) represents no skin discomfort/pain, and the right-hand boundary (100) represents worst possible skin discomfort/pain. The distance from the mark to the left-hand boundary was recorded.~A negative change from baseline indicates improvement in skin discomfort/pain." (NCT03774875)
Timeframe: Baseline, week 32 and week 52
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | -22.6 | -31.0 |
| Placebo / Apremilast 30 mg | -28.4 | -35.0 |
(NCT03774875)
Timeframe: Baseline and week 2, week 4, and week 16
| Intervention | cm (Mean) | ||
|---|---|---|---|
| Week 2 | Week 4 | Week 16 | |
| Apremilast 30 mg | 0.2 | -0.3 | -0.9 |
| Placebo | -0.2 | -0.1 | 0.1 |
(NCT03774875)
Timeframe: From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast.
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alanine Aminotransferase > 3 × ULN | Albumin < 25 g/L | Alkaline Phosphatase > 400 U/L | Aspartate Aminotransferase > 3 × ULN | Bilirubin > 1.8 × ULN | Blood Urea Nitrogen > 15 mmol/L | Calcium < 1.8 mmol/L | Calcium > 3.0 mmol/L | Cholesterol > 7.8 mmol/L | Creatinine > 1.7 × ULN | Glucose < 2.8 mmol/L | Glucose > 13.9 mmol/L | Hemoglobin A1C (Fasting) > 9% | Lactate Dehydrogenase > 3 × ULN | Potassium < 3.0 mmol/L | Potassium > 5.5 mmol/L | Sodium < 130 mmol/L | Sodium > 150 mmol/L | Triglycerides > 3.4 mmol/L | Hemoglobin: Female < 85 g/L, Male < 105 g/L | Hemoglobin: Female > 170 g/L, Male > 185 g/L | Leukocytes < 1.5 × 10^9/L | Lymphocytes < 0.8 × 10^9/L | Neutrophils, Segmented < 1.0 × 10^9/L | Platelets < 75 × 10^9/L | Platelets > 600 × 10^9/L | |
| Apremilast 30 mg | 2 | 0 | 0 | 1 | 1 | 2 | 1 | 0 | 3 | 1 | 0 | 7 | 3 | 0 | 0 | 2 | 0 | 0 | 22 | 1 | 0 | 0 | 3 | 0 | 2 | 0 |
"Marked laboratory abnormalities are defined for each parameter below.~ULN = upper limit of normal" (NCT03774875)
Timeframe: 16 weeks
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alanine Aminotransferase > 3 × ULN | Albumin < 25 g/L | Alkaline Phosphatase > 400 U/L | Aspartate Aminotransferase > 3 × ULN | Bilirubin (umol/L) > 1.8 × ULN | Blood Urea Nitrogen > 15 mmol/L | Calcium < 1.8 mmol/L | Calcium > 3.0 mmol/L | Cholesterol > 7.8 mmol/L | Creatinine > 1.7 × ULN | Glucose < 2.8 mmol/L | Glucose > 13.9 mmol/L | Hemoglobin A1C (Fasting) > 9% | Lactate Dehydrogenase > 3 × ULN | Potassium < 3.0 mmol/L | Potassium > 5.5 mmol/L | Sodium < 130 mmol/L | Sodium > 150 mmol/L | Triglycerides > 3.4 mmol/L | Hemoglobin: Female < 85 g/L, Male < 105 g/L | Hemoglobin: Female > 170 g/L, Male > 185 g/L | Leukocytes < 1.5 × 10^9/L | Lymphocytes < 0.8 × 10^9/L | Neutrophils, Segmented < 1.0 × 10^9/L | Platelets < 75 × 10^9/L | Platelets > 600 × 10^9/L | |
| Apremilast 30 mg | 2 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 1 | 1 | 0 | 3 | 3 | 0 | 0 | 1 | 0 | 0 | 6 | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| Placebo | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
"An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening of a preexisting condition was considered an AE.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event. The Investigator assessed the severity/intensity of each event as mild, moderate, or severe based on level of symptoms." (NCT03774875)
Timeframe: From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast.
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Drug-related TEAE | Severe TEAEs | Serious TEAEs | Serious drug-related TEAE | TEAE leading to drug interruption | TEAE leading to drug withdrawal | TEAE leading to death | |
| Apremilast 30 mg | 217 | 152 | 14 | 18 | 2 | 19 | 31 | 0 |
"An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening of a preexisting condition was considered an AE.~A serious adverse event (SAE) is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event. The Investigator assessed the severity/intensity of each event as mild, moderate, or severe based on level of symptoms." (NCT03774875)
Timeframe: From first dose of study drug to week 16 or up to 28 days after last dose for participants who didn't enter the apremilast extension period.
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any TEAE | Drug-related TEAE | Severe TEAEs | Serious TEAEs | Serious drug-related TEAE | TEAE leading to drug interruption | TEAE leading to drug withdrawal | TEAE leading to death | |
| Apremilast 30 mg | 152 | 113 | 10 | 8 | 1 | 9 | 18 | 0 |
| Placebo | 54 | 26 | 1 | 0 | 0 | 0 | 8 | 0 |
"Body surface area is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT03774875)
Timeframe: Baseline, week 32 and week 52
| Intervention | percent change (Mean) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | -40.2 | -32.0 |
| Placebo / Apremilast 30 mg | -49.5 | -49.9 |
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life (QOL). The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Placebo | 41.3 |
| Apremilast 30 mg | 73.3 |
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life (QOL). The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. (NCT03774875)
Timeframe: Baseline, week 32 and week 52
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | 68.4 | 79.6 |
| Placebo / Apremilast 30 mg | 68.1 | 76.8 |
The PASI score is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant and the values for each anatomic region are summed to yield the PASI score. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT03774875)
Timeframe: Week 32 and week 52
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | 40.1 | 37.5 |
| Placebo / Apremilast 30 mg | 58.0 | 50.7 |
The PBI is a validated patient-reported instrument to assess patient-relevant benefits of psoriasis treatment. Prior to starting study treatment, participants were asked to assess the importance of a series of treatment goals (from not important to very important) by completing the Patient Needs Questionnaire (PNQ). After a period of treatment (32 weeks and 52 weeks), participants were then asked to assess the extent to which these goals were achieved (from not at all to very) by completing the Patient Benefit Questionnaire (PBQ). The Patient Benefit Index represents the benefits realized as a function of most important needs. The PBI score ranges from 0 (no benefit) to 4 (maximum benefit). (NCT03774875)
Timeframe: Week 32 and week 52
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 32 | Week 52 | |
| Apremilast 30 mg | 67.8 | 63.8 |
| Placebo / Apremilast 30 mg | 66.7 | 65.2 |
"Body surface area is a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or handprint), which equates to approximately 1% of total BSA." (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 18.5 |
| Apremilast 30 mg | -19.8 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to psoriasis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 52
| Intervention | percent impairment (Mean) |
|---|---|
| Placebo / Apremilast 30 mg | -4.6 |
| Apremilast 30 mg | -3.2 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 52
| Intervention | percent impairment (Mean) |
|---|---|
| Placebo / Apremilast 30 mg | -21.0 |
| Apremilast 30 mg | -24.4 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which psoriasis affected their regular daily unpaid activities, measured on a VAS from 1 (no effect on daily activities) to 10 (psoriasis completely prevented daily activities). A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 52
| Intervention | percent impairment (Mean) |
|---|---|
| Placebo / Apremilast 30 mg | -32.7 |
| Apremilast 30 mg | -30.5 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent impairment while working was derived from the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent impairment (Least Squares Mean) |
|---|---|
| Placebo | -11.5 |
| Apremilast 30 mg | -13.9 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent overall work impairment takes into account both hours missed due to psoriasis symptoms and the participant's assessment of the degree to which psoriasis affected their productivity while working. A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent impairment (Least Squares Mean) |
|---|---|
| Placebo | -13.2 |
| Apremilast 30 mg | -13.8 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent activity impairment is derived from the patient's assessment of the degree to which psoriasis affected their regular daily unpaid activities, measured on a VAS from 1 (no effect on daily activities) to 10 (psoriasis completely prevented daily activities). A higher percentage indicates greater impairment and less productivity, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent impairment (Least Squares Mean) |
|---|---|
| Placebo | -13.4 |
| Apremilast 30 mg | -21.2 |
The WPAI: PSO is a self-administered questionnaire designed to address impairment to the work productivity and activity of participants due to psoriasis in the past 7 days. Percent of work time missed is derived from the number of hours of work missed due to psoriasis symptoms as a percentage of total hours that should have been worked. A higher percentage indicates more hours missed, and a negative change from baseline indicates improvement. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent impairment (Least Squares Mean) |
|---|---|
| Placebo | -4.1 |
| Apremilast 30 mg | -0.9 |
(NCT03774875)
Timeframe: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
| Intervention | cm (Mean) |
|---|---|
| Apremilast 30 mg | -0.8 |
"Participants were asked to indicate their level of skin discomfort/pain in the past week by placing a vertical stroke on a 100 mm horizontal line on which the left-hand boundary (0) represents no skin discomfort/pain, and the right-hand boundary (100) represents worst possible skin discomfort/pain. The distance from the mark to the left-hand boundary was recorded.~A negative change from baseline indicates improvement in skin discomfort/pain." (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | -5.4 |
| Apremilast 30 mg | -21.5 |
(NCT03774875)
Timeframe: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
| Intervention | beats/minute (Mean) |
|---|---|
| Apremilast 30 mg | 1.0 |
(NCT03774875)
Timeframe: Baseline and week 2, week 4, and week 16
| Intervention | beats/minute (Mean) | ||
|---|---|---|---|
| Week 2 | Week 4 | Week 16 | |
| Apremilast 30 mg | 3.4 | 3.5 | 2.0 |
| Placebo | 0.3 | -0.4 | 1.0 |
The DLQI is a 10-item skin disease-specific questionnaire used to evaluate the impact of skin disease on health-related quality of life. The items address symptoms and feelings, daily activities, leisure, work/school, personal relationships, and issues with treatment. Questions are answered on a 4-point scale from 0 (not at all/not applicable) to 3 (very much). Item scores are added to provide a total score from 0 to 30, with higher scores indicating greater impairment of QOL. A negative change from baseline indicates improvement in quality of life. (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | -3.4 |
| Apremilast 30 mg | -8.7 |
(NCT03774875)
Timeframe: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
| Intervention | kg (Mean) |
|---|---|
| Apremilast 30 mg | -1.20 |
"The Itch Numeric Rating Scale (NRS) asked participants to assess the worst severity of itch experienced over the past 24 hours on an 11-point scale anchored from 0, representing 'no itching' to 10, representing 'worst itch imaginable'.~A negative change from baseline indicates improvement in itch severity." (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Placebo | -0.9 |
| Apremilast 30 mg | -2.5 |
"EQ-5D measures the participants general health state as a vertical VAS and 5 quality of life domains: mobility, self-care, main activity (work, study, housework, family/leisure activities), pain/discomfort, and anxiety/depression. Each dimension is rated on three levels (no problems, some/moderate problems, extreme problems). An EQ-5D summary index is derived by applying a formula that attaches values (weights) to each of the levels in each dimension.~EQ-5D index values were derived using the UK scoring algorithm, where a higher score indicates a better health state. The range of the score is from -0.224 to 1, with 0 corresponding to death, 1 corresponding to full health, and negative numbers indicate health states worse than death. A positive change from baseline indicates improvement." (NCT03774875)
Timeframe: Baseline and week 16
| Intervention | percent change (Least Squares Mean) |
|---|---|
| Placebo | 165.9 |
| Apremilast 30 mg | 17.8 |
"The modified sPGA-G is the assessment by the Investigator of the participant's psoriasis lesions' overall disease severity in the genital area at the time of evaluation. The modified sPGA-G is a 5-point scale ranging from clear (0), almost clear (1), mild (2), moderate (3), to severe (4), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, plaque elevation, and scaling.~A modified sPGA-G response is defined as modified sPGA-G score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16.~Missing values were imputed using the multiple imputation (MI) method. Two-sided 95% confidence intervals (CIs) for the within-group proportions were based on the Wilson-score method." (NCT03777436)
Timeframe: Baseline and Week 16 of the Placebo-controlled Phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 19.5 |
| Placebo-controlled Phase: Apremilast 30 mg | 39.6 |
"The sPGA is the assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 3 (moderate) to 4 (severe), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation.~An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16.~Missing values were imputed using the MI method. Two-sided 95% CIs for the within-group proportions were based on the Wilson-score method." (NCT03777436)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 6.9 |
| Placebo-controlled Phase: Apremilast 30 mg | 22.2 |
"The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No), and if No, then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot).~Total scores have a possible range of 0-30, where 0 represents the best score, and 30 represents the worst health-related quality of life.~A negative change from Baseline indicates an improvement in health-related quality of life scores." (NCT03777436)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Scores on a scale (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase: Placebo | -2.6 |
| Placebo-controlled Phase: Apremilast 30 mg | -5.3 |
"The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or handprints (each entire palmar surface or handprint equates to approximately 1% of total BSA).~A negative change from Baseline indicates a reduction of affected BSA.~Based on mixed-effect model for repeated measures (MMRM) model." (NCT03777436)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Change in percentage of affected BSA (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase: Placebo | -0.79 |
| Placebo-controlled Phase: Apremilast 30 mg | -4.12 |
"The GPI-NRS is a self-reported measure where participants were asked to assess their psoriasis symptoms in the genital area and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch.~A GPI-NRS response is defined as ≥ 4 point reduction (improvement) from Baseline.~Missing values were imputed using the MI method. Two-sided 95% CIs for the within-group proportions were based on the Wilson-score method." (NCT03777436)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Percentage of participants (Number) |
|---|---|
| Placebo-controlled Phase: Placebo | 19.6 |
| Placebo-controlled Phase: Apremilast 30 mg | 47.3 |
"The GPSS is a self-reported measure where participants were asked to assess each of their psoriasis symptoms (itch, pain, discomfort, stinging, burning, redness, scaling, and cracking) in the genital area and select a number on a scale of 0-10, where 0 represents no symptoms, and 10 represents the worst imaginable.~Results from each symptom assessment were summed to generate a total GPSS score ranging from 0 (no genital psoriasis symptoms) to 80 (worst imaginable genital psoriasis symptoms).~A negative change from Baseline indicates an improvement in genital psoriasis symptoms." (NCT03777436)
Timeframe: Baseline and Week 16 of the placebo-controlled phase
| Intervention | Score on a scale (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase: Placebo | -5.3 |
| Placebo-controlled Phase: Apremilast 30 mg | -20.5 |
The Health Assessment Questionnaire Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement. (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.293 | -0.383 |
"The Evaluator's Global Assessment of Disease Activity evaluates how active a participant's PsA was on the day of the assessment. Disease activity was assessed on a 0 to 10 numeric rating scale (NRS) where 0 represents no arthritis activity, and 10 represents extreme active arthritis. A negative change from baseline indicates improvement." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -2.7 | -2.8 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis).~Synovitis and bone marrow edema were each scored from 0 (none/normal) to 3 (severe) at each joint. The total score for synovitis ranges from 0 to 36 and the total score for BME ranges from 0 to 72 since this is scored at both proximal and distal regions of each joint.~The PsAMRIS composite score of BME and synovitis is calculated as: BME score + 2 × synovitis score. The score ranges from 0 (normal) to 144 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM including change from baseline of composite score of BME and synovitis as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.19 | -1.54 |
"The c-DAPSA is a measure of PsA disease activity, associated with functional and structural outcomes.~C-DAPSA is calculated as the sum of the following measures:~Tender joint count 68 (TJC68);~Swollen joint count 66 (SJC66);~Patient global assessment of disease activity measured on a numerical rating scale (NRS) from 0 (not active) to 10 (very active); and~Pain measured on a NRS from 0 (none) to 10 (worst pain imaginable).~The c-DAPSA score ranges from 0 to 154, where a higher score indicates greater disease activity. A negative change from baseline indicates improvement." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -15.3 | -17.2 |
"BASDAI is a composite score based on a self-administered survey of six questions with each answered on a 0 to 10 NRS. The 6 questions assess the five major symptoms relevant to spondyloarthropathies: 1) fatigue; 2) spinal pain; 3) peripheral joint pain/swelling; 4) areas of localized tenderness; 5a) morning stiffness severity upon wakening; 5b) morning stiffness duration upon wakening.~To give each of the 5 symptoms equal weighting, the mean of the two scores relating to morning stiffness (questions 5 and 6) is taken. The final BASDAI score is calculated as the mean of the 5 items. The BASDAI score ranges from 0 to 10, with higher scores reflecting greater disease activity. A negative change from baseline indicates improvement.~BASDAI was analyzed in participants deemed to have PsA spondylitis by the investigator and with BASDAI item 2 score ≥ 4 at baseline)." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.94 | -2.01 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis).~Tenosynovitis is inflammation of the protective sheath (synovial membrane) that surrounds tendons.~Flexor tenosynovitis was scored from 0 to 3 at MCP, PIP and DIP joints of fingers 2 to 5 (total of 12 joints) where a score of 0 is none; 1: < 1/2 tendon thickness; 2: ≥ 1/2 and < 1 tendon thickness; 3: ≥ 1 tendon thickness. The overall tenosynovitis score ranges from 0 (none) to 36 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM including change from baseline in tenosynovitis score as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and Weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.64 | -0.78 |
A total of 78 joints (including the distal interphalangeal joints of the fingers and toes) were examined for pain or tenderness. (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | joints (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -7.9 | -8.4 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis).~Synovitis is inflammation of the synovial membrane, connective tissue that lines the inside of the joint.~Synovitis was scored from 0 to 3 at MCP, PIP and DIP joints of fingers 2 to 5 (total of 12 joints), where score 0 is normal, and a score of 1 is mild, 2 is moderate, and 3 is severe. The overall synovitis score ranges from 0 (normal) to 36 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM including change from baseline in synovitis score as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.47 | -0.65 |
A total of 76 joints (including the distal interphalangeal joints of the fingers and toes) were examined for swelling. (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | joints (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -5.8 | -6.3 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis).~Periarticular inflammation refers to inflammation of the tissues surrounding the joint, including the periosteum and the entheses, but not the tendon sheaths.~Periarticular inflammation was scored 0 (absent) or 1 (present) separately at volar and dorsal aspects of the same 12 joint regions as evaluated for synovitis and flexor tenosynovitis. The score for periarticular inflammation ranges from 0 (absent) to 24 (present at all joints). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM including change from baseline in periarticular inflammation as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.49 | -0.59 |
"Dactylitis is characterized by the swelling of the entire finger or toe. Dactylitis was assessed using the Leeds Dactylitis Index (LDI). LDI measures the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference is multiplied by a tenderness score from 0 to 3, where 0 = No Tenderness, 1 = Tender, 2 = Tender and wince, 3 = Tender and withdraw. The dactylitis score is the sum of the individual scores for each digit, where 0 indicates no dactylitis and higher scores represent worse dactylitis. A negative change from baseline indicates improvement.~Pre-existing dactylitis is defined as a baseline LDI score greater than 0." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -34.38 | -38.71 |
"PASDAS is a measure of disease activity derived from the following variables:~Physician and patient global assessment of disease activity (assessed on a 0-10 NRS, then multiplied by 10)~68 tender joint count~66 swollen joint count~Short Form-36 Questionnaire (SF-36) physical component summary score (general health status on a scale from 0-100)~Tender dactylitis count (each digit assessed for tender dactylitis; total score 0-20)~Leeds enthesitis index (enthesitis assessed at 6 sites; total score of 0-6)~C-reactive protein (CRP) level (mg/L) The composite score is a weighted index that ranges from 0 to 10, with worse disease activity represented by higher scores. A negative change from baseline indicates improvement." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.752 | -1.833 |
"The PsAID consists of 12 physical and psychological domains: pain, fatigue, skin, work and/or leisure activities, function, discomfort, sleep, coping, anxiety, embarrassment and/or shame, social life, and depression.~Each domain is scored on a NRS rom 0 to 10. The final score is derived as a weighted sum of each domain score, divided by 20, and has a range from 0 (best status) to 10 (worst status). A negative change from baseline indicates improvement." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.352 | -1.612 |
The Subject's Assessment of Pain is an assessment of how much pain a participant had on average during the past week due to psoriatic arthritis. The score ranges from 0-10 based on a numerical rating scale, where 0 represents 'No Pain' and 10 represents 'Pain As Bad As You Can Imagine'. A negative change from baseline indicates improvement. (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.4 | -2.0 |
"Dactylitis is characterized by the swelling of the entire finger or toe. Dactylitis was assessed using the Leeds Dactylitis Index (LDI). LDI measures the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference is multiplied by a tenderness score from 0 to 3 , where 0 = No Tenderness, 1 = Tender, 2 = Tender and wince, 3 = Tender and withdraw). The LDI score is the sum of the individual scores for each digit, where 0 is no dactylitis and higher scores represent worse dactylitis.~Resolution of dactylitis is defined as a LDI score of 0 for participants with dactylitis (LDI score > 0) at baseline." (NCT03783026)
Timeframe: Weeks 24 and 48
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | 89.2 | 93.3 |
The Patient's Global Assessment is an assessment of how active a participant's arthritis was on average during the past week. The score ranges from 0 to 10 based on a numerical rating scale, where 0 represents 'Very Well' and 10 represents 'Very Poor'. A negative change from baseline indicates improvement. (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.3 | -1.6 |
"A TEAE is any adverse event (AE) that began or worsened on or after the first dose of apremilast and no later than 28 days after the last dose.~A serious adverse event is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event.~For each AE, the Investigator assessed the severity/intensity of the event as mild, moderate, or severe (symptoms causing severe discomfort/pain, interference with daily activities, and requiring medical, surgical or drug therapy). The Investigator also assessed whether each event was suspected to be related to study drug based on whether there was evidence to suggest a causal relationship." (NCT03783026)
Timeframe: From first dose of study drug up to 28 days after last dose; up to 52 weeks.
| Intervention | Participants (Count of Participants) | |||||||
|---|---|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | Any drug-related TEAE | Any severe TEAE | Any serious TEAE | Any serious drug-related TEAE | Any TEAE leading to study drug interruption | Any TEAE leading to study drug withdrawal | Any TEAE leading to death | |
| Apremilast | 95 | 60 | 6 | 6 | 0 | 12 | 15 | 0 |
"Enthesitis was assessed by whole body MRI according to the OMERACT MRI Whole-Body Score for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) scoring system. Thirty-three entheseal sites were assessed for soft tissue inflammation (STI) and 34 sites for osteitis, including the shoulder, pelvis, knees and feet, each on a scale from 0 (none) to 3 (severe).~The Total Peripheral Enthesitis Inflammation score is calculated by adding up all the enthesitis (STI and osteitis) scores and ranges from 0 to 201, with higher scores reflecting greater disease severity. A negative change from baseline indicates improvement.~WB-MRI endpoints were analyzed using a MMRM including change from baseline as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.17 | -0.52 |
"Bone marrow edema (BME) is a buildup of fluid inside the bones. The OMERACT PsAMRIS scoring system assesses BME at the proximal and distal regions of MCP, PIP, and DIP joints of fingers 2 to 5 of the most affected hand. BME is assessed on a scale of 0-3 based on the proportion of bone with edema, compared to the assessed bone volume (articular surface to a depth of 1 cm), judged on all available images; where 0: no edema; 1: 1-33% of bone edema; 2: 34-66% of bone edema; 3: 67-100% of bone edema. The overall score ranges from 0 (none) to 72 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM with change from baseline BME score as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.22 | -0.39 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand.~Bone erosion (loss of bone) was assessed at the distal and proximal regions of each joint on a scale of 0-10, based on the proportion of eroded bone compared to the assessed bone volume, judged on all available images: 0: no erosion; 1: 1-10% of bone eroded; 2: 11-20%, etc. The assessed bone volume is from the articular surface (or its best estimated position if absent) to a depth of 1 cm. The total erosion score ranges from 0 (none) to 240 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM with baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -0.01 | 0.03 |
"Enthesitis is inflammation of the sites where tendons or ligaments insert into the bone. The SPARCC Enthesitis Index assesses 16 unique sites for tenderness recorded as either present (1) or absent (0) for an overall score range of 0 to 16. A higher count represents greater enthesitis burden. A negative change from baseline indicates improvement.~Pre-existing enthesopathy was defined as a baseline SPARCC score greater than 0." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.8 | -2.3 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis).~Synovitis, flexor tenosynovitis, and bone marrow edema were scored from 0 (none/normal) to 3 (severe) at each joint. The total scores for synovitis and tenosynovitis range from 0 to 36 and the total score for BME ranges from 0 to 72 since both proximal and distal regions of each joint were scored.~The PsAMRIS composite inflammation score is calculated as: BME score + 2 × synovitis score + 2 × tenosynovitis score, and ranges from 0 (normal) to 216 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM with change from baseline as the dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and week 48
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Apremilast | -2.91 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand (the hand with the greater inflammatory burden of swollen joints and/or dactylitis).~Synovitis, flexor tenosynovitis, and bone marrow edema were scored from 0 (none/normal) to 3 (severe) at each joint. The total scores for synovitis and tenosynovitis range from 0 to 36 and the total score for BME ranges from 0 to 72 since both proximal and distal regions of each joint were scored.~The PsAMRIS composite inflammation score is calculated as: BME score + 2 × synovitis score + 2 × tenosynovitis score, and ranges from 0 (normal) to 216 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a mixed-effects model for repeated measures (MMRM) with change from baseline as the dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and week 24
| Intervention | score on a scale (Least Squares Mean) |
|---|---|
| Apremilast | -2.32 |
"Inflammation in joints (arthritis) and at entheses (enthesitis) were assessed separately for soft tissues (synovitis at joints, soft tissue inflammation at entheses) and bone (osteitis) by whole body MRI according to the OMERACT MRI-WIPE scoring system. Each entheseal and joint was scored on a scale from 0 (none) to 3 (severe).~The total peripheral inflammation index is the sum of peripheral enthesitis and peripheral joints inflammation index scores, and ranges from 0 to 738, with higher scores reflecting greater disease severity. A negative change from baseline indicates improvement.~WB MRI endpoints were analyzed using a MMRM including change from baseline as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -3.49 | -4.06 |
"Joint inflammation was assessed by whole body MRI according to the OMERACT MRI-WIPE scoring system. Eighty-three peripheral joints were assessed for synovitis and 96 sites for osteitis at the shoulder, hands, pelvis, knees and feet on a semiquantitative scale from 0 (none) to 3 (severe).~The Peripheral Joint Inflammation score is calculated by adding up all the joint (synovitis and osteitis) scores and ranges from 0 to 537, with higher scores reflecting greater disease severity. A negative change from baseline indicates improvement.~WB MRI endpoints were analyzed using a MMRM including change from baseline as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -3.38 | -3.58 |
"LEI is a validated tool for the assessment of enthesitis in PsA patients. Tenderness was assessed at 6 sites of tendon insertion (lateral epicondyle, left and right, medial femoral condyle, left and right, and Achilles tendon insertion, left and right). Tenderness was recorded as either present (1) or absent (0) for each of the 6 sites, for an overall score range of 0 to 6. A higher count represents a greater enthesitis burden. A negative change from baseline indicates improvement.~Pre-existing enthesopathy was defined as a baseline LEI score greater than 0." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -1.3 | -1.5 |
"PsAMRIS is a validated MRI scoring system that assesses MCP, PIP, and DIP joints of fingers 2 to 5 of the most affected hand.~Bone erosion (loss of bone) was assessed at the distal and proximal regions of each joint on a scale of 0 to 10, based on the proportion of eroded bone compared to the assessed bone volume, where 0 is no erosion; 1: 1-10% of bone eroded; 2: 11-20%, etc. The total erosion score is from 0 (none) to 240 (severe).~Bone proliferation (abnormal bone formation in the periarticular region) was scored at each joint as 0 (absent) or 1 (present). The total proliferation score is from 0 to 12 (present at all joints) The total damage score includes the erosion and bone proliferation scores, calculated as: Erosion score + 20 × bone proliferation score, and ranges from 0 (none) to 480 (worst). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM with baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | 0.22 | 0.50 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand.~Synovitis, flexor tenosynovitis, and bone marrow edema were each scored from 0 (none/normal) to 3 (severe) at each joint. Periarticular inflammation was scored 0 (absent) or 1 (present) separately at volar and dorsal aspects of the same 12 joints. The scores for synovitis and tenosynovitis range from 0 to 36, the score for BME is from 0 to 72 and the periarticular inflammation score is from 0 to 24.~The PsAMRIS total inflammation score is calculated as: BME score + 2 × synovitis score + 2 × tenosynovitis score + 3 × periarticular inflammation, and ranges from 0 (normal) to 288 (severe). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM with change from baseline score as dependent variable; baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | -3.62 | -4.35 |
"PsAMRIS is a validated MRI scoring system that assesses metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of fingers 2 to 5 of the most affected hand.~Bone proliferation (abnormal bone formation in the periarticular region such as at the entheses and across the joint) was scored at each joint as 0 (absent) or 1 (present). The total proliferation score ranges from 0 (none) to 12 (present at all joints). A negative change from baseline indicates improvement.~This endpoint was analyzed using a MMRM with baseline value, scanner type and time as independent variables." (NCT03783026)
Timeframe: Baseline and weeks 24 and 48
| Intervention | score on a scale (Least Squares Mean) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | 0.01 | 0.02 |
Enthesitis is inflammation of the sites where tendons or ligaments insert into the bone. The SPARCC Enthesitis Index assesses 16 unique sites for tenderness recorded as either present (1) or absent (0) for an overall score range of 0 to 16. A higher count represents greater enthesitis burden. Resolution of SPARCC enthesitis is defined as achieving a SPARCC index score of 0 for participants with baseline SPARCC enthesitis (SPARCC index score > 0). (NCT03783026)
Timeframe: Weeks 24 and 48
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | 46.9 | 57.0 |
LEI is a validated tool for the assessment of enthesitis in PsA patients. Tenderness was assessed at 6 sites of tendon insertion (lateral epicondyle, left and right, medial femoral condyle, left and right, and Achilles tendon insertion, left and right). Tenderness was recorded as either present (1) or absent (0) for each of the 6 sites, for an overall score range of 0 to 6. A higher count represents a greater enthesitis burden. Resolution of LEI enthesitis is defined as a LEI score of 0 for participants with baseline LEI enthesitis (LEI score > 0). (NCT03783026)
Timeframe: Weeks 24 and 48
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 24 | Week 48 | |
| Apremilast | 56.4 | 62.3 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT03930186)
Timeframe: Weeks 16 and 32
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | 43.4 | 46.7 |
"One target thumb nail or fingernail representing the worst nail psoriasis involvement was selected for assessment at Baseline.~The nail matrix was assessed for presence of any of the nail matrix features (pitting, leukonychia red spots in the lunula, crumbling) graded on a scale of 0 (none) to 4 (present in all 4 quadrants).~The nail bed was assessed for the presence of any nail bed features (onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop (salmon patch dyschroma) on a scale from 0 (none) to 4 (present in all quadrants).~The sum of the nail matrix and nail bed scores is the total score and ranges from 0 to 8 (worst)." (NCT03930186)
Timeframe: Weeks 16 and 32
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | 44.7 | 57.9 |
"The Patient Benefit Index (PBI) is used to assess patient-relevant benefits of psoriasis treatment as a function of the most important needs identified by the participant before the start of treatment.~Participants were asked to assess the benefits of treatment by completing the Patient Benefit Questionnaire (PBQ), which consists of 25 treatment goal statements scored from 0 (not at all) to 4 (very).~The PBI is calculated for each participant by weighing the achievement values of each statement by their importance to the individual patient as assessed prior to the start of treatment. The PBI ranges from 0 (no benefit) to 4 (maximum benefit)." (NCT03930186)
Timeframe: Weeks 16 and 32
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | 91.4 | 88.2 |
The ScPGA assesses scalp involvement of psoriasis based on scalp plaque elevation, scaling, and erythema. The 5-point ScPGA scale ranges from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe). (NCT03930186)
Timeframe: Weeks 16 and 32
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | 52.3 | 50.8 |
"The sPGA is an assessment by the Investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale, ranging from 0 (clear) to 4 (severe).~The National Psoriasis Foundation Psoriasis Score version of a static PGA is calculated by averaging the total body erythema, induration, and desquamation scores. The overall scores are as follows:~0 = Clear;~= Almost Clear;~= Mild;~= Moderate;~= Severe.~The percentage of participants with a sPGA response was estimated using a multiple imputation method from 100 imputed data sets." (NCT03930186)
Timeframe: Week 16
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 43.7 |
"The sPGA is an assessment by the Investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale, ranging from 0 (clear) to 4 (severe).~The National Psoriasis Foundation Psoriasis Score version of a static PGA is calculated by averaging the total body erythema, induration, and desquamation scores. The overall scores are as follows:~0 = Clear;~= Almost Clear;~= Mild;~= Moderate;~= Severe." (NCT03930186)
Timeframe: Week 32
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast | 40.8 |
"The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much), except for Question 7, which first asks whether the participant's skin prevented them from working or studying (Yes (score = 3) or No (score = 0), then If No, the participant is asked how much their skin was a problem at work or studying over the last week, with responses from 0 (not at all), 1 (a little), or 2 (a lot).~The DLQI total score ranges from 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best. A negative change from baseline indicates improvement." (NCT03930186)
Timeframe: Baseline and weeks 16 and 32
| Intervention | scores on a scale (Mean) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | -2.2 | -2.3 |
"The overall body surface area affected by psoriasis was estimated based on the palm area of the participant's hand, which equates to approximately 1% of total body surface area. BSA affected by psoriasis is expressed as a percentage of total body surface area.~A negative change from baseline indicates improvement." (NCT03930186)
Timeframe: Baseline and weeks 16 and 32
| Intervention | percent BSA (Mean) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | -7.86 | -8.32 |
"Shiratori's Pruritus Severity Score is a pruritus (itchiness) severity assessment tool used in Japan. Daytime and nighttime pruritus were evaluated and scored separately. Daytime pruritus was rated on a five-grade scale: 0 (absent), 1 (endurable without scratching; minimal), 2 (subsides with slight scratching; mild), 3 (subsides with considerable scratching; moderate), or 4 (not subsiding with scratching, which prompts repeated scratching; severe).~Nighttime pruritus was rated on a five-grade scale: 0 (absent), 1 (slight itching at bedtime but not causing intentional scratching; no difficulty sleeping because of pruritus), 2 (slight itching that subsides with scratching; no difficulty sleeping because of pruritus), 3 (difficulty sleeping because of pruritus that resolves with scratching; unconscious scratching occurs during sleep), or 4 (severe difficulty sleeping due to pruritus; frequent scratching that worsens pruritus).~A negative change from baseline indicates improvement." (NCT03930186)
Timeframe: Baseline and weeks 2, 16, and 32
| Intervention | units on a scale (Mean) | |||||
|---|---|---|---|---|---|---|
| Daytime: Week 2 | Daytime: Week 16 | Daytime: Week 32 | Nighttime: Week 2 | Nighttime: Week 16 | Nighttime: Week 32 | |
| Apremilast | -0.5 | -0.7 | -0.7 | -0.4 | -0.7 | -0.7 |
The Treatment Satisfaction Questionnaire for Medication (TSQM) version II is a self-administered instrument to understand a participant's satisfaction on current therapy. The TSQM comprises 11 items across 4 domains focusing on effectiveness (Item 1 and 2), side effects (Item 4 to 6), convenience (Item 7 to 9), and global satisfaction (Item 10 and 11). With the exception of Item 3 (experience any side effects; yes or no), all items have five or seven responses. Item scores are summed to give four domain scores, which are in turn transformed to a scale from 0 (extremely dissatisfied) to 100 (extremely satisfied). (NCT03930186)
Timeframe: Baseline and weeks 16 and 32
| Intervention | scores on a scale (Mean) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Effectiveness: Baseline | Effectiveness: Week 16 | Effectiveness: Week 32 | Side Effects: Baseline | Side Effects: Week 16 | Side Effects: Week 32 | Convenience: Baseline | Convenience: Week 16 | Convenience: Week 32 | Global Satisfaction: Baseline | Global Satisfaction: Week 16 | Global Satisfaction: Week 32 | |
| Apremilast | 52.25 | 67.41 | 68.93 | 97.37 | 90.40 | 93.21 | 56.43 | 70.34 | 70.48 | 55.43 | 71.21 | 70.71 |
"The Investigator assessed the severity/intensity of each adverse event as:~Mild (asymptomatic or mild symptoms; intervention not indicated; activities of daily life (ADLs) minimally or not affected); Moderate (symptom(s) cause moderate discomfort; local or noninvasive intervention indicated; more than minimal interference with ADLs but able to carry out daily social and functional activities; drug therapy may be required); Severe (symptoms causing severe discomfort/pain; symptoms requiring medical/surgical attention/intervention; interference with ADLs including inability to perform daily social and functional activities; drug therapy required).~A serious adverse event is any AE occurring at any dose that:~Resulted in death;~Was life-threatening;~Required inpatient hospitalization or prolongation of existing hospitalization;~Resulted in persistent or significant disability/incapacity;~Was a congenital anomaly/birth defect;~Constituted an important medical event." (NCT03930186)
Timeframe: From first dose of study drug until at least 28 days after last dose; up to 36 weeks.
| Intervention | Participants (Count of Participants) | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Any treatment-emergent adverse event | Drug-related TEAE | Severe TEAE | Serious TEAE | Severe drug-related TEAE | Serious drug-related TEAE | TEAE leading to drug interruption | TEAE leading to drug withdrawal | TEAE leading to death | |
| Apremilast | 115 | 88 | 4 | 4 | 1 | 1 | 3 | 7 | 0 |
Participants were asked to indicate how much itch they have had due to psoriasis in the past week by placing a vertical stroke on a 100 mm line on which the left-hand boundary (0 mm) represented no itch, and the right-hand boundary (100 mm) represented worst itch imaginable. The distance from the mark to the left-hand boundary was recorded. A negative change from baseline indicates improvement. (NCT03930186)
Timeframe: Baseline and weeks 2, 16, and 32
| Intervention | percent change (Mean) | ||
|---|---|---|---|
| Week 2 | Week 16 | Week 32 | |
| Apremilast | -36.96 | -28.05 | -25.29 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. A negative change from baseline indicates improvement. (NCT03930186)
Timeframe: Baseline and weeks 16 and 32
| Intervention | percent change (Mean) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | -69.61 | -69.48 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. (NCT03930186)
Timeframe: Weeks 16 and 32
| Intervention | percentage of participants (Number) | |
|---|---|---|
| Week 16 | Week 32 | |
| Apremilast | 79.6 | 75.0 |
"PPPASI-50 is defined as >= 50 percent decrease in PPPASI total score from baseline.~PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease." (NCT04057937)
Timeframe: At Week 16
| Intervention | Percentage of Partcipants (Number) |
|---|---|
| Placebo-controlled Phase - Placebo | 40.9 |
| Placebo-controlled Phase - Apremilast 30 mg BID | 78.3 |
"PPPASI-75 is defined as >=75 percent decrease in PPPASI total score from baseline.~PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Missing values were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder." (NCT04057937)
Timeframe: Weeks 2 to 16
| Intervention | Percentage of Partcipants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | Week 16 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | 2.2 | 10.9 | 21.7 | 19.6 | 30.4 | 30.4 | 37.0 | 43.5 |
| Placebo-controlled Phase - Placebo | 2.3 | 4.5 | 9.1 | 11.4 | 11.4 | 13.6 | 13.6 | 15.9 |
"The AUC for PPPASI total score from baseline through Week 16 is the sum of the AUCs in each time interval specified by the dates of the visits and is calculated based on the linear trapezoidal method.~PPPASI is a disease-specific efficacy assessment tool to evaluate 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease." (NCT04057937)
Timeframe: Baseline to Week 16
| Intervention | Scores * Day (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase - Placebo | 1911.74 |
| Placebo-controlled Phase - Apremilast 30 mg BID | 1337.49 |
The AUC for PPSI total score from baseline through Week 16 is the sum of the AUCs in each time interval specified by the dates of the visits and is calculated based on the linear trapezoidal method. PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. (NCT04057937)
Timeframe: Baseline to Week 16
| Intervention | Scores * Day (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase - Placebo | 725.62 |
| Placebo-controlled Phase - Apremilast 30 mg BID | 564.63 |
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Change from baseline based on a mixed-effects model for repeated measures with a positive change indicating a worsening of symptoms. (NCT04057937)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase - Placebo | -11.03 |
| Placebo-controlled Phase - Apremilast 30 mg BID | -16.48 |
PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. Change from baseline based on a mixed-effects model for repeated measures with a positive change indicating a worsening of symptoms. (NCT04057937)
Timeframe: Baseline and Week 16
| Intervention | Units on a scale (Least Squares Mean) |
|---|---|
| Placebo-controlled Phase - Placebo | -2.56 |
| Placebo-controlled Phase - Apremilast 30 mg BID | -4.19 |
"PPPASI-50 is defined as >= 50 percent decrease in PPPASI total score from baseline.~PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. Missing values at were imputed using non-responder imputation (NRI) as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder." (NCT04057937)
Timeframe: Weeks 2 to 14
| Intervention | Percentage of Participants (Number) | ||||||
|---|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | 30.4 | 52.2 | 69.6 | 65.2 | 71.7 | 69.6 | 73.9 |
| Placebo-controlled Phase - Placebo | 2.3 | 18.2 | 18.2 | 43.2 | 34.1 | 34.1 | 47.7 |
Participants assessed the degree of both pruritus itching and skin discomfort/pain as symptoms on hands and feet caused by PPP on a VAS. Each score ranged from 0 to 100. The left-hand boundary (0) on the VAS represents no itch/pain and the right-hand boundary (100) represents itch/pain as severe as can be imagined by participant. (NCT04057937)
Timeframe: Baseline and Weeks 2,4,6,8,12,16
| Intervention | Units on scale (Mean) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Itching Week 2 | Itching Week 4 | Itching Week 6 | Itching Week 8 | Itching Week 12 | Itching Week 16 | Discomfort/Pain Week 2 | Discomfort/Pain Week 4 | Discomfort/Pain Week 6 | Discomfort/Pain Week 8 | Discomfort/Pain Week 12 | Discomfort/Pain Week 16 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | -25.0 | -22.7 | -22.4 | -24.8 | -28.3 | -26.8 | -20.2 | -21.6 | -22.4 | -22.0 | -27.6 | -25.3 |
| Placebo-controlled Phase - Placebo | -2.4 | -7.9 | -9.3 | -19.0 | -14.9 | -10.5 | -0.7 | -6.9 | -6.7 | -15.5 | -14.1 | -13.5 |
PPPASI is a disease-specific efficacy assessment tool to evaluated for 3 signs of the disease (erythema, pustules/vesicle and desquamation/scale) as sub-scores on palms or soles. The PPPASI total scores are calculated by sum of the sub-scores and range from 0 to 72 with a higher score indicating more severe disease. A positive change from baseline indicates a worsening of symptoms. (NCT04057937)
Timeframe: Baseline to Week 16
| Intervention | Percent Change (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | Week 16 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | -36.62 | -48.96 | -55.06 | -57.11 | -60.85 | -61.22 | -63.78 | -64.33 |
| Placebo-controlled Phase - Placebo | -11.09 | -23.82 | -30.15 | -42.41 | -36.52 | -42.30 | -45.00 | -42.35 |
PPSI is a disease-specific assessment tool for grading the severity of PPP lesions. Evaluation of skin lesion sites are assessed separately for erythema, pustules/vesicle and desquamation/scale, which are each rated on a scale of 0 to 4. The PPSI produces a total numeric score that ranges from 0 to 12. A higher score indicates more severe disease. A positive change from baseline indicates a worsening of symptoms. (NCT04057937)
Timeframe: Baseline to Week 16
| Intervention | Percent Change (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | Week 16 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | -24.70 | -34.58 | -40.50 | -40.76 | -44.22 | -46.47 | -50.16 | -48.96 |
| Placebo-controlled Phase - Placebo | -6.25 | -13.84 | -20.02 | -30.12 | -27.42 | -31.18 | -34.98 | -30.90 |
"The PGA for palms and soles was used to determine the participants PPP lesions on palms and soles. Lesions on palms and soles were graded based on the following scales:~0 = Clear~= Almost clear/Minimal~= Mild~= Moderate~= Severe~= Very severe.~The percentage of of participants with at least a 2 grade improvement from baseline (stringent responders) are reported. issing values at were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder." (NCT04057937)
Timeframe: Weeks 2 to 16
| Intervention | Percentage of Participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | Week 16 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | 2.2 | 4.3 | 4.3 | 6.5 | 10.9 | 15.2 | 17.4 | 17.4 |
| Placebo-controlled Phase - Placebo | 0.0 | 2.3 | 2.3 | 9.1 | 9.1 | 9.1 | 9.1 | 4.5 |
"The PGA for palms and soles was used to determine the participants PPP lesions on palms and soles. Lesions on palms and soles were graded based on the following scales:~0 = Clear~= Almost clear/Minimal~= Mild~= Moderate~= Severe~= Very severe.~The percentage of of participants with a post baseline score of 0 or 1 (responders) are reported. Missing values at were imputed using NRI as the primary method, by which a participant without sufficient data for the response determination was considered a non-responder." (NCT04057937)
Timeframe: Weeks 2 to 16
| Intervention | Percentage of Participants (Number) | |||||||
|---|---|---|---|---|---|---|---|---|
| Week 2 | Week 4 | Week 6 | Week 8 | Week 10 | Week 12 | Week 14 | Week 16 | |
| Placebo-controlled Phase - Apremilast 30 mg BID | 2.2 | 4.3 | 4.3 | 8.7 | 13.0 | 15.2 | 17.4 | 19.6 |
| Placebo-controlled Phase - Placebo | 0.0 | 2.3 | 2.3 | 9.1 | 9.1 | 9.1 | 9.1 | 4.5 |
PPPASI 50 response defined as a 50% decrease in PPPASI from baseline. (NCT04572997)
Timeframe: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| Visit 3 - Week 4 | Visit 4 - Week 12 | Visit 5 - End of Study - Week 20 | |
| Full Analysis Set (FAS) | 7 | 12 | 13 |
| Per Protocol Set (PPS) | 7 | 12 | 13 |
"The DLQI is a dermatology-specific quality of life instrument designed to assess the impact of a disease on the patient's daily life which is also validated for PPP. It is a 10-item questionnaire and can be used to assess 6 different aspects: symptoms and feelings, leisure, daily activities, work or school performance, personal relationship and treatment. The DLQI was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life was impaired.~Meaning of DLQI scores:~0 to 1 = No effect at all on patient's life~2 to 5 = Small effect on patient's life~6 to 10 = Moderate effect on patient's life~11 to 20 = Very large effect on patient's life~21 to 30 = Extremely large effect on patient's life" (NCT04572997)
Timeframe: At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20).
| Intervention | DLQI Score (Median) | ||
|---|---|---|---|
| Visit 2 - Baseline | Visit 4 - Week 12 | Visit 5 - End of Study - Week 20 | |
| Full Analysis Set (FAS) | 8.50 | 2.50 | 2.00 |
| Per Protocol Set (PPS) | 8.00 | 2.50 | 2.00 |
Percentage change from baseline in Pustules count after 20 weeks of treatment with Apremilast (NCT04572997)
Timeframe: At Visit 2 (Baseline) and Visit 5 (End of Study - Week 20)
| Intervention | Percent change (Median) |
|---|---|
| Full Analysis Set - LOCF | -76.3 |
| Per Protocol Set (PPS) | -79.82 |
The PPPASI assess palms of hands and soles of feet for psoriasis involvement. The PPPASI score range from 0-72, with higher scores indicating more severe disease. (NCT04572997)
Timeframe: PPPASI Score at baseline and Week 20.
| Intervention | PPPASI Score (Median) | |
|---|---|---|
| Visit 2 - Baseline | Visit 5 - End of Study - Week 20 | |
| Full Analysis Set - LOCF | 16.50 | 8.10 |
| Full Analysis Set (FAS) | 16.50 | 7.65 |
| Per Protocol Set (PPS) | 15.85 | 7.65 |
The H&F PGA describes the severity of psoriasis on the hands and/or feet using five categories ranging from 0 (clear) to 4 (severe). (NCT04572997)
Timeframe: At Visit 2 (Baseline), Visit 3 (Week 4) , Visit 4 (Week 12) and Visit 5 (Week 20).
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Visit 2 - Baseline72520890 | Visit 2 - Baseline72520891 | Visit 3 - Week 472520890 | Visit 3 - Week 472520891 | Visit 4 - Week 1272520890 | Visit 4 - Week 1272520891 | Visit 5 - End of Study - Week 2072520890 | Visit 5 - End of Study - Week 2072520891 | |||||||||||||||||||||||||||||||||
| 0 clear | 1 almost clear | 2 mild | 3 moderate | 4 severe | ||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 0 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 0 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 2 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 2 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 19 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 18 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 1 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 10 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 9 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 3 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 3 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 9 | |||||||||||||||||||||||||||||||||||||||
| Full Analysis Set (FAS) | 8 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 1 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 10 | |||||||||||||||||||||||||||||||||||||||
| Per Protocol Set (PPS) | 8 | |||||||||||||||||||||||||||||||||||||||
The dynamic H&F PGA describes the global improvement compared with baseline. It relies on the physician's memory of the baseline severity to evaluate the level of alteration. The categories vary between 0 (cleared) and 6 (worse). (NCT04572997)
Timeframe: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Intervention | Participants (Count of Participants) | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Visit 3 - Week 472520894 | Visit 4 - Week 1272520894 | Visit 5 - End of Study - Week 2072520894 | |||||||||||||||||||
| 5 fair | 6 worse | 1 excellent | 2 good | 3 slight | 4 unchanged | 0 cleared | |||||||||||||||
| Per Protocol Set (PPS) | 3 | ||||||||||||||||||||
| Per Protocol Set (PPS) | 4 | ||||||||||||||||||||
| Per Protocol Set (PPS) | 7 | ||||||||||||||||||||
| Per Protocol Set (PPS) | 0 | ||||||||||||||||||||
| Per Protocol Set (PPS) | 5 | ||||||||||||||||||||
| Per Protocol Set (PPS) | 2 | ||||||||||||||||||||
| Per Protocol Set (PPS) | 6 | ||||||||||||||||||||
VAS was used to assess pruritus/itch. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (at 0 mm) represented no pruritus/itch, and the right-hand boundary (at 100 mm) represented pruritus/itch as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more pruritus/itch (worse outcomes). (NCT04572997)
Timeframe: At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Intervention | Units on a scale (Median) | |||
|---|---|---|---|---|
| Visit 2 - Baseline | Visit 3 - Week 4 | Visit 4 - Week 12 | Visit 5 - End of Study - Week 20 | |
| Full Analysis Set (FAS) | 31.0 | 2.0 | 25.0 | 12.0 |
| Per Protocol Set (PPS) | 29.5 | 11.0 | 24.0 | 11.5 |
VAS was used to assess discomfort/pain. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary represented no discomfort/pain (at 0 mm), and the right-hand boundary (at 100 mm) represented discomfort/pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more discomfort/pain (worse conditions). (NCT04572997)
Timeframe: At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Intervention | Units on a scale (Median) | |||
|---|---|---|---|---|
| Visit 2 - Baseline | Visit 3 - Week 4 | Visit 4 - Week 12 | Visit 5 - End of Study - Week 20 | |
| Full Analysis Set (FAS) | 44.0 | 4.0 | 2.0 | 9.0 |
| Per Protocol Set (PPS) | 37.5 | 3.0 | 1.5 | 7.5 |
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. (NCT04572997)
Timeframe: At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Intervention | PASI Score (Median) | |||
|---|---|---|---|---|
| Visit 2 - Baseline | Visit 3 - Week 4 | Visit 4 - Week 12 | Visit 5-End of Study-Week 20 | |
| Per Protocol Set (PPS) | 3.85 | 2.27 | 0.5 | 0.95 |
Patients experiencing a 50% and 75% decrease in Pustules count from baseline (NCT04572997)
Timeframe: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study-Week 20).
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Pustules count 50: Visit 3 - Week 4 | Pustules count 50: Visit 4 - Week 12 | Pustules count 50: Visit 5-End of Study- Week 20 | Pustules count 75: Visit 3 - Week 4 | Pustules count 75: Visit 4 - Week 12 | Pustules count 75: Visit 5-End of Study- Week 20 | |
| Full Analysis Set (FAS) | 13 | 18 | 16 | 8 | 14 | 12 |
| Per Protocol Set (PPS) | 14 | 17 | 16 | 9 | 14 | 12 |
PPPASI 75 response defined as a 75% decrease in PPPASI from baseline. (NCT04572997)
Timeframe: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| Visit 3 - Week 4 | Visit 4 - Week 12 | Visit 5 - End of Study - Week 20 | |
| Full Analysis Set (FAS) | 2 | 6 | 3 |
| Per Protocol Set (PPS) | 2 | 6 | 3 |
"Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29.~The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study." (NCT04590586)
Timeframe: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
| Intervention | days (Median) |
|---|---|
| Lanadelumab + Standard of Care | 10.0 |
| Lanadelumab Placebo Control | 15.5 |
"Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.~The clinical severity status 8-point ordinal scale scores are:~Death~Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Baseline (Day 1) and Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Lanadelumab + Standard of Care | 72.0 |
| Lanadelumab Placebo Control | 63.3 |
"Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.~Clinical severity status 8-point ordinal scale:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Day 60
| Intervention | percentage of participants (Number) |
|---|---|
| Zilucoplan + Standard of Care | 55.0 |
| Zilucoplan Placebo Control | 64.0 |
All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29. (NCT04590586)
Timeframe: Day 1 to Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Zilucoplan + Standard of Care | 18.0 |
| Zilucoplan Placebo Control | 24.0 |
"Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.~The clinical severity status 8-point ordinal scale scores are:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Baseline (Day 1) and Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Zilucoplan + Standard of Care | 66.0 |
| Zilucoplan Placebo Control | 69.3 |
"Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29.~The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study." (NCT04590586)
Timeframe: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
| Intervention | days (Median) |
|---|---|
| Zilucoplan + Standard of Care | 14.0 |
| Zilucoplan Placebo Control | 15.0 |
"An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.~The Investigator assessed the intensity of each AE according to the CTCAE grades:~Grade 1 Mild; asymptomatic or mild symptoms;~Grade 2 Moderate; minimal, local or noninvasive intervention indicated;~Grade 3 Severe or medically significant, not immediately life-threatening;~Grade 4 Life-threatening; urgent intervention indicated;~Grade 5 Death due to AE." (NCT04590586)
Timeframe: From first dose of study drug to end of study (Day 60)
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE with a CTCAE grade ≥ 3 | Serious TEAE | TEAE leading to dose modification | TEAE leading to discontinuation of study drug | |
| Apremilast + Standard of Care | 102 | 48 | 51 | 16 | 9 |
| Apremilast Placebo + Standard of Care | 100 | 54 | 55 | 6 | 11 |
| Apremilast Placebo Control | 103 | 57 | 57 | 6 | 12 |
"Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.~Clinical severity status 8-point ordinal scale:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Day 8, Day 15, and Day 29
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Day 8 | Day 15 | Day 29 | |
| Apremilast + Standard of Care | 36.6 | 57.7 | 66.0 |
| Apremilast Placebo Control | 35.8 | 60.0 | 72.1 |
"An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A Serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.~The Investigator assessed the intensity of each AE according to the Common Terminology Criteria for Adverse Events (CTCAE):~Grade 1 Mild; asymptomatic or mild symptoms;~Grade 2 Moderate; minimal, local or noninvasive intervention indicated;~Grade 3 Severe or medically significant, not immediately life-threatening;~Grade 4 Life-threatening; urgent intervention indicated;~Grade 5 Death due to AE." (NCT04590586)
Timeframe: From first dose of study drug to end of study (Day 60)
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE with a CTCAE grade ≥ 3 | Serious TEAE | TEAE leading to dose modification | TEAE leading to discontinuation of study drug | |
| Lanadelumab + Standard of Care | 17 | 11 | 11 | 2 | 1 |
| Lanadelumab Placebo + Standard of Care | 1 | 1 | 1 | 0 | 0 |
| Lanadelumab Placebo Control | 22 | 18 | 18 | 3 | 5 |
"Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.~Clinical severity status 8-point ordinal scale:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Day 8, Day 15, and Day 29
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Day 8 | Day 15 | Day 29 | |
| Lanadelumab + Standard of Care | 44.0 | 56.0 | 60.0 |
| Lanadelumab Placebo Control | 36.7 | 56.7 | 63.3 |
"An adverse event is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to study treatment. A TEAE is an AE that occurs after the first dose of study drug. A serious AE is any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, resulted in persistent disability/incapacity, a congenital anomaly/birth defect, or an important medical event that may jeopardize the patient or require intervention to prevent an outcome listed above.~The Investigator assessed the intensity of each AE according to the CTCAE grades:~Grade 1 Mild; asymptomatic or mild symptoms;~Grade 2 Moderate; minimal, local or noninvasive intervention indicated;~Grade 3 Severe or medically significant, not immediately life-threatening;~Grade 4 Life-threatening; urgent intervention indicated;~Grade 5 Death due to AE." (NCT04590586)
Timeframe: From first dose of study drug to end of study (Day 60)
| Intervention | Participants (Count of Participants) | ||||
|---|---|---|---|---|---|
| Any treatment-emergent adverse event (TEAE) | TEAE with a CTCAE grade ≥ 3 | Serious TEAE | TEAE leading to dose modification | TEAE leading to discontinuation of study drug | |
| Zilucoplan Placebo + Standard of Care | 4 | 3 | 2 | 0 | 1 |
| Zilucoplan Placebo Control | 47 | 29 | 29 | 5 | 5 |
| Zilucoplan+ Standard of Care | 65 | 34 | 31 | 0 | 7 |
"Clinical recovery is defined as being fit for discharge, i.e., the achievement of a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who discontinued the study on or before Days 8, 15, or 29 or with a missing clinical recovery status were considered as not having clinical recovery at each respective time point.~Clinical severity status 8-point ordinal scale:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Day 8, Day 15, and Day 29
| Intervention | percentage of participants (Number) | ||
|---|---|---|---|
| Day 8 | Day 15 | Day 29 | |
| Zilucoplan + Standard of Care | 33.0 | 53.0 | 60.0 |
| Zilucoplan Placebo Control | 30.7 | 53.3 | 66.7 |
"The clinical severity status 8-point ordinal scale scores are:~Death~Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)~Hospitalized, on noninvasive ventilation or high flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities~Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint." (NCT04590586)
Timeframe: Day 8, Day 15, and Day 29
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 872273936 | Day 872273930 | Day 1572273936 | Day 1572273930 | Day 2972273930 | Day 2972273936 | |||||||||||||||||||||||||||||||||||||||||||||||||
| 5 (Hospitalized, not requiring supplemental oxygen | 6 (Hospitalized, not requiring supplemental oxygen | 7 (Not hospitalized, limitation on activities and/ | 8 (Not hospitalized, no limitations on activities) | Missing | 1 (Death or discharged to hospice care) | 2 (Hospitalized on invasive mechanical ventilation | 3 (Hospitalized on noninvasive ventilation or high | 4 (Hospitalized, requiring supplemental oxygen) | ||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 20 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 25 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 26 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 26 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 31 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 40 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 36 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 33 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 38 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 34 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 16 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 46 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 48 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 78 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 79 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 31 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 34 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 110 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast Placebo Control | 104 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Apremilast + Standard of Care | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery. (NCT04590586)
Timeframe: Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Lanadelumab + Standard of Care | 52.0 |
| Lanadelumab Placebo Control | 56.7 |
"The clinical severity status 8-point ordinal scale scores are:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities~Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint." (NCT04590586)
Timeframe: Day 8, Day 15, and Day 29
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 872273932 | Day 872273931 | Day 1572273932 | Day 1572273931 | Day 2972273931 | Day 2972273932 | |||||||||||||||||||||||||||||||||||||||||||||||||
| 1 (Death or discharged to hospice care) | 2 (Hospitalized on invasive mechanical ventilation | 3 (Hospitalized on noninvasive ventilation or high | 4 (Hospitalized, requiring supplemental oxygen) | 5 (Hospitalized, not requiring supplemental oxygen | 6 (Hospitalized, not requiring supplemental oxygen | 7 (Not hospitalized, limitation on activities and/ | 8 (Not hospitalized, no limitations on activities) | Missing | ||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 24 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 22 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 16 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 25 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 31 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 26 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 14 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 18 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 20 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan + Standard of Care | 44 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 35 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Zilucoplan Placebo Control | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery. (NCT04590586)
Timeframe: Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast + Standard of Care | 59.8 |
| Apremilast Placebo Control | 63.7 |
"Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.~Clinical severity status 8-point ordinal scale:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Day 60
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast + Standard of Care | 66.0 |
| Apremilast Placebo Control | 66.3 |
"The clinical severity status 8-point ordinal scale scores are:~Death~Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)~Hospitalized, on noninvasive ventilation or high flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities~Participants with a score of 7 who were discharged to hospice care are counted with participants with a score of 1 (death) for this endpoint." (NCT04590586)
Timeframe: Day 8, Day 15, and Day 29
| Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Day 872273928 | Day 872273927 | Day 1572273928 | Day 1572273927 | Day 2972273927 | Day 2972273928 | |||||||||||||||||||||||||||||||||||||||||||||||||
| 1 (Death or discharged to hospice care) | 2 (Hospitalized on invasive mechanical ventilation | 3 (Hospitalized on noninvasive ventilation or high | 4 (Hospitalized, requiring supplemental oxygen) | 5 (Hospitalized, not requiring supplemental oxygen | 6 (Hospitalized, not requiring supplemental oxygen | 7 (Not hospitalized, limitation on activities and/ | Missing | 8 (Not hospitalized, no limitations on activities) | ||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab Placebo Control | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 0 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lanadelumab + Standard of Care | 12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29. (NCT04590586)
Timeframe: Day 1 to Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast + Standard of Care | 17.5 |
| Apremilast Placebo Control | 17.4 |
All-cause mortality is death due to any cause. Participants with an unknown alive/death status on Day 29 were considered alive for this analysis, with the exception of patients with a score of 7 who were discharged to hospice care before or on Day 29. (NCT04590586)
Timeframe: Day 1 to Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Lanadelumab + Standard of Care | 32.0 |
| Lanadelumab Placebo Control | 30.0 |
"Fit for discharge is defined as achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale. Participants with an ordinal scale score of 7 must not have been discharged to hospice care to be considered as fit for discharge. Participants with a missing clinical severity score at Day 29 were considered as not having met the event at Day 29.~The clinical severity status 8-point ordinal scale scores are:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high-flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise)~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Baseline (Day 1) and Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Apremilast + Standard of Care | 74.7 |
| Apremilast Placebo Control | 77.9 |
"Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29.~The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study." (NCT04590586)
Timeframe: Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29
| Intervention | days (Median) |
|---|---|
| Apremilast + Standard of Care | 14.0 |
| Apremilast Placebo Control | 14.0 |
Oxygen-free recovery at Day 29 is defined as being alive, discharged, and not receiving supplemental oxygen at Day 29. Participants who reached a score of 7 on the ordinal scale for clinical severity who were discharged to hospice care before or on Day 29 were considered as not discharged at Day 29. Participants with a missing oxygen-free recovery status at Day 29 were considered as not having an oxygen-free recovery. (NCT04590586)
Timeframe: Day 29
| Intervention | percentage of participants (Number) |
|---|---|
| Zilucoplan + Standard of Care | 54.0 |
| Zilucoplan Placebo Control | 60.0 |
"Sustained clinical recovery is defined as being fit for discharge (achieving a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale) by Day 29, without re-hospitalization by Day 60. Participants with a score of 7 discharged to hospice care were not considered fit for discharge. Participants who died or discontinued from study or with a missing clinical recovery status at Day 60 were not considered having sustained clinical recovery.~Clinical severity status 8-point ordinal scale:~Death~Hospitalized, on invasive mechanical ventilation or ECMO~Hospitalized, on noninvasive ventilation or high flow oxygen devices~Hospitalized, requiring supplemental oxygen~Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care~Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care~Not hospitalized, limitation on activities and/or requiring home oxygen~Not hospitalized, no limitations on activities" (NCT04590586)
Timeframe: Day 60
| Intervention | percentage of participants (Number) |
|---|---|
| Lanadelumab + Standard of Care | 40.0 |
| Lanadelumab Placebo Control | 56.7 |
The area under the concentration-time curve of apremilast in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is reported. (NCT04811573)
Timeframe: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
| Intervention | hour * nanogram / milliliter (h*ng/mL) (Geometric Mean) |
|---|---|
| EU-Otezla Fasted (A; Tfasted) | 2420 |
| US-Otezla Fasted (B; R1fasted) | 2460 |
| EU-Otezla Fed (C; Tfed) | 2600 |
| US-Otezla Fed (D; R1fed) | 2600 |
| Japan-Otezla Fasted (E; R2fasted) | 2370 |
The area under the concentration-time curve of apremilast in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. (NCT04811573)
Timeframe: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
| Intervention | hour * nanogram / milliliter (h*ng/mL) (Geometric Mean) |
|---|---|
| EU-Otezla Fasted (A; Tfasted) | 2390 |
| US-Otezla Fasted (B; R1fasted) | 2430 |
| EU-Otezla Fed (C; Tfed) | 2580 |
| US-Otezla Fed (D; R1fed) | 2580 |
| Japan-Otezla Fasted (E; R2fasted) | 2350 |
The maximum measured concentration of apremilast in plasma (Cmax) is reported. (NCT04811573)
Timeframe: 1 hour (h) before and 30 minutes (min), 1h, 1h30min, 2h, 2h30min, 3h, 3h30min, 4h, 5h, 6h, 8h, 11h, 15h, 24h, 36h, 48h after study drug administration.
| Intervention | nanogram / milliliter (ng/mL) (Geometric Mean) |
|---|---|
| EU-Otezla Fasted (A; Tfasted) | 298 |
| US-Otezla Fasted (B; R1fasted) | 301 |
| EU-Otezla Fed (C; Tfed) | 303 |
| US-Otezla Fed (D; R1fed) | 271 |
| Japan-Otezla Fasted (E; R2fasted) | 299 |
| Substance | Relationship Strength | Studies | Trials | Classes | Roles |
|---|---|---|---|---|---|
| benzoic acid Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.. benzoic acid : A compound comprising a benzene ring core carrying a carboxylic acid substituent.. aromatic carboxylic acid : Any carboxylic acid in which the carboxy group is directly bonded to an aromatic ring. | 7.21 | 1 | 0 | benzoic acids | algal metabolite; antimicrobial food preservative; drug allergen; EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor; EC 3.1.1.3 (triacylglycerol lipase) inhibitor; human xenobiotic metabolite; plant metabolite |
| butyric acid Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.. butyrate : A short-chain fatty acid anion that is the conjugate base of butyric acid, obtained by deprotonation of the carboxy group.. butyric acid : A straight-chain saturated fatty acid that is butane in which one of the terminal methyl groups has been oxidised to a carboxy group. | 3.56 | 1 | 1 | fatty acid 4:0; straight-chain saturated fatty acid | human urinary metabolite; Mycoplasma genitalium metabolite |
| chlorine chloride : A halide anion formed when chlorine picks up an electron to form an an anion. | 3.56 | 1 | 1 | halide anion; monoatomic chlorine | cofactor; Escherichia coli metabolite; human metabolite |
| bupropion Bupropion: A propiophenone-derived antidepressant and antismoking agent that inhibits the uptake of DOPAMINE.. bupropion : An aromatic ketone that is propiophenone carrying a tert-butylamino group at position 2 and a chloro substituent at position 3 on the phenyl ring. | 2.08 | 1 | 0 | aromatic ketone; monochlorobenzenes; secondary amino compound | antidepressant; environmental contaminant; xenobiotic |
| formaldehyde paraform: polymerized formaldehyde; RN given refers to parent cpd; used in root canal therapy | 3.56 | 1 | 1 | aldehyde; one-carbon compound | allergen; carcinogenic agent; disinfectant; EC 3.5.1.4 (amidase) inhibitor; environmental contaminant; Escherichia coli metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| niacinamide nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group. | 4.15 | 2 | 0 | pyridine alkaloid; pyridinecarboxamide; vitamin B3 | anti-inflammatory agent; antioxidant; cofactor; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; Escherichia coli metabolite; geroprotector; human urinary metabolite; metabolite; mouse metabolite; neuroprotective agent; Saccharomyces cerevisiae metabolite; Sir2 inhibitor |
| uric acid Uric Acid: An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.. uric acid : An oxopurine that is the final oxidation product of purine metabolism.. 6-hydroxy-1H-purine-2,8(7H,9H)-dione : A tautomer of uric acid having oxo groups at C-2 and C-8 and a hydroxy group at C-6.. 7,9-dihydro-1H-purine-2,6,8(3H)-trione : An oxopurine in which the purine ring is substituted by oxo groups at positions 2, 6, and 8. | 2.15 | 1 | 0 | uric acid | Escherichia coli metabolite; human metabolite; mouse metabolite |
| theophylline [no description available] | 3.35 | 1 | 0 | dimethylxanthine | adenosine receptor antagonist; anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; drug metabolite; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; fungal metabolite; human blood serum metabolite; immunomodulator; muscle relaxant; vasodilator agent |
| amiodarone Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.. amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. | 2.08 | 1 | 0 | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| amoxapine Amoxapine: The N-demethylated derivative of the antipsychotic agent LOXAPINE that works by blocking the reuptake of norepinephrine, serotonin, or both; it also blocks dopamine receptors. Amoxapine is used for the treatment of depression.. amoxapine : A dibenzooxazepine compound having a chloro substituent at the 2-position and a piperazin-1-yl group at the 11-position. | 2.08 | 1 | 0 | dibenzooxazepine | adrenergic uptake inhibitor; antidepressant; dopaminergic antagonist; geroprotector; serotonin uptake inhibitor |
| astemizole Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects.. astemizole : A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position. | 2.08 | 1 | 0 | benzimidazoles; piperidines | anti-allergic agent; anticoronaviral agent; H1-receptor antagonist |
| azathioprine Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed). azathioprine : A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS. | 3.63 | 2 | 0 | aryl sulfide; C-nitro compound; imidazoles; thiopurine | antimetabolite; antineoplastic agent; carcinogenic agent; DNA synthesis inhibitor; hepatotoxic agent; immunosuppressive agent; prodrug |
| bromhexine Bromhexine: A mucolytic agent used in the treatment of respiratory disorders associated with viscid or excessive mucus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p744). bromhexine : A substituted aniline that is 2,4-dibromoaniline which is substituted at position 6 by a [cyclohexyl(methyl)amino]methyl group. It is used (as the monohydrochloride salt) as a mucolytic for the treatment of respiratory disorders associated with productive cough (i.e. a cough characterised by the production of sputum). | 2.08 | 1 | 0 | organobromine compound; substituted aniline; tertiary amino compound | mucolytic |
| buspirone Buspirone: An anxiolytic agent and serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the BENZODIAZAPINES, but it has an efficacy comparable to DIAZEPAM.. buspirone : An azaspiro compound that is 8-azaspiro[4.5]decane-7,9-dione substituted at the nitrogen atom by a 4-(piperazin-1-yl)butyl group which in turn is substituted by a pyrimidin-2-yl group at the N(4) position. | 2.08 | 1 | 0 | azaspiro compound; N-alkylpiperazine; N-arylpiperazine; organic heteropolycyclic compound; piperidones; pyrimidines | anxiolytic drug; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; sedative; serotonergic agonist |
| caffeine [no description available] | 3.35 | 1 | 0 | purine alkaloid; trimethylxanthine | adenosine A2A receptor antagonist; adenosine receptor antagonist; adjuvant; central nervous system stimulant; diuretic; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; environmental contaminant; food additive; fungal metabolite; geroprotector; human blood serum metabolite; mouse metabolite; mutagen; plant metabolite; psychotropic drug; ryanodine receptor agonist; xenobiotic |
| celecoxib [no description available] | 2.08 | 1 | 0 | organofluorine compound; pyrazoles; sulfonamide; toluenes | cyclooxygenase 2 inhibitor; geroprotector; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| chlorpromazine Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.. chlorpromazine : A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety. | 2.08 | 1 | 0 | organochlorine compound; phenothiazines; tertiary amine | anticoronaviral agent; antiemetic; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; phenothiazine antipsychotic drug |
| cilostamide cilostamide: selective inhibitor of cyclic AMP phosphodiesterase & platelet aggregation; structure | 2.21 | 1 | 0 | quinolines | |
| dapsone [no description available] | 3.27 | 1 | 0 | substituted aniline; sulfone | anti-inflammatory drug; antiinfective agent; antimalarial; leprostatic drug |
| desipramine Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.. desipramine : A dibenzoazepine consisting of 10,11-dihydro-5H-dibenzo[b,f]azepine substituted on nitrogen with a 3-(methylamino)propyl group. | 2.08 | 1 | 0 | dibenzoazepine; secondary amino compound | adrenergic uptake inhibitor; alpha-adrenergic antagonist; antidepressant; cholinergic antagonist; drug allergen; EC 3.1.4.12 (sphingomyelin phosphodiesterase) inhibitor; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; H1-receptor antagonist; serotonin uptake inhibitor |
| diazepam Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.. diazepam : A 1,4-benzodiazepinone that is 1,3-dihydro-2H-1,4-benzodiazepin-2-one substituted by a chloro group at position 7, a methyl group at position 1 and a phenyl group at position 5. | 2.6 | 1 | 0 | 1,4-benzodiazepinone; organochlorine compound | anticonvulsant; anxiolytic drug; environmental contaminant; sedative; xenobiotic |
| diclofenac Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.. diclofenac : A monocarboxylic acid consisting of phenylacetic acid having a (2,6-dichlorophenyl)amino group at the 2-position. | 3.56 | 1 | 1 | amino acid; aromatic amine; dichlorobenzene; monocarboxylic acid; secondary amino compound | antipyretic; drug allergen; EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor; environmental contaminant; non-narcotic analgesic; non-steroidal anti-inflammatory drug; xenobiotic |
| dipyridamole Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752). dipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots. | 2.21 | 1 | 0 | piperidines; pyrimidopyrimidine; tertiary amino compound; tetrol | adenosine phosphodiesterase inhibitor; EC 3.5.4.4 (adenosine deaminase) inhibitor; platelet aggregation inhibitor; vasodilator agent |
| donepezil Donepezil: An indan and piperidine derivative that acts as a selective and reversible inhibitor of ACETYLCHOLINESTERASE. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate DEMENTIA in ALZHEIMER DISEASE.. donepezil : A racemate comprising equimolar amounts of (R)- and (S)-donepezil. A centrally acting reversible acetylcholinesterase inhibitor, its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine.. 2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindan-1-one : A member of the class of indanones that is 5,6-dimethoxyindan-1-one which is substituted at position 2 by an (N-benzylpiperidin-4-yl)methyl group. | 2.25 | 1 | 0 | aromatic ether; indanones; piperidines; racemate | EC 3.1.1.7 (acetylcholinesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; nootropic agent |
| doxepin Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.. doxepin : A dibenzooxepine that is 6,11-dihydrodibenzo[b,e]oxepine substituted by a 3-(dimethylamino)propylidene group at position 11. It is used as an antidepressant drug. | 3.23 | 1 | 0 | dibenzooxepine; tertiary amino compound | antidepressant |
| etazolate Etazolate: A potent phosphodiesterase inhibitor proposed as an antipsychotic agent.. etazolate : A pyrazolopyridine that is 1H-pyrazolo[3,4-b]pyridine which is substituted at positions 1, 4, and 5 by ethyl, 2-isopropylidenehydrazino, and ethoxycarbonyl groups, respectively. A phosphodiesterase IV inhibitor with antidepressant and anxiolytic properties. | 3.35 | 1 | 0 | ethyl ester; hydrazone; pyrazolopyridine | alpha-secretase activator; antidepressant; antipsychotic agent; anxiolytic drug; GABA agent; neuroprotective agent; phosphodiesterase IV inhibitor |
| flecainide Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.. flecainide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with the primary amino group of piperidin-2-ylmethylamine. An antiarrhythmic agent used (in the form of its acetate salt) to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart). | 2.08 | 1 | 0 | aromatic ether; monocarboxylic acid amide; organofluorine compound; piperidines | anti-arrhythmia drug |
| flutamide Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. | 2.08 | 1 | 0 | (trifluoromethyl)benzenes; monocarboxylic acid amide | androgen antagonist; antineoplastic agent |
| granisetron [no description available] | 2.08 | 1 | 0 | aromatic amide; indazoles | |
| haloperidol Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279). haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. | 2.08 | 1 | 0 | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| hydroxyurea [no description available] | 3.21 | 1 | 0 | one-carbon compound; ureas | antimetabolite; antimitotic; antineoplastic agent; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; genotoxin; immunomodulator; radical scavenger; teratogenic agent |
| ibudilast [no description available] | 3.35 | 1 | 0 | pyrazolopyridine | |
| imipramine Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.. imipramine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)propyl group at the nitrogen atom. | 2.08 | 1 | 0 | dibenzoazepine | adrenergic uptake inhibitor; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor |
| itraconazole [no description available] | 2.08 | 1 | 0 | piperazines | |
| ketanserin Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.. ketanserin : A member of the class of quinazolines that is quinazoline-2,4(1H,3H)-dione which is substituted at position 3 by a 2-[4-(p-fluorobenzoyl)piperidin-1-yl]ethyl group. | 2.08 | 1 | 0 | aromatic ketone; organofluorine compound; piperidines; quinazolines | alpha-adrenergic antagonist; antihypertensive agent; cardiovascular drug; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; serotonergic antagonist |
| ketoconazole 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively. | 9.4 | 1 | 1 | dichlorobenzene; dioxolane; ether; imidazoles; N-acylpiperazine; N-arylpiperazine | |
| lansoprazole Lansoprazole: A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers. | 2.08 | 1 | 0 | benzimidazoles; pyridines; sulfoxide | anti-ulcer drug; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor |
| leflunomide Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.. leflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide. | 4.16 | 2 | 0 | (trifluoromethyl)benzenes; isoxazoles; monocarboxylic acid amide | antineoplastic agent; antiparasitic agent; EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; hepatotoxic agent; immunosuppressive agent; non-steroidal anti-inflammatory drug; prodrug; pyrimidine synthesis inhibitor; tyrosine kinase inhibitor |
| letrozole [no description available] | 3.56 | 1 | 1 | nitrile; triazoles | antineoplastic agent; EC 1.14.14.14 (aromatase) inhibitor |
| loxapine Loxapine: An antipsychotic agent used in SCHIZOPHRENIA. | 2.08 | 1 | 0 | dibenzooxazepine | antipsychotic agent; dopaminergic antagonist |
| metoprolol Metoprolol: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.. metoprolol : A propanolamine that is 1-(propan-2-ylamino)propan-2-ol substituted by a 4-(2-methoxyethyl)phenoxy group at position 1. | 2.08 | 1 | 0 | aromatic ether; propanolamine; secondary alcohol; secondary amino compound | antihypertensive agent; beta-adrenergic antagonist; environmental contaminant; geroprotector; xenobiotic |
| mianserin Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.. mianserin : A dibenzoazepine (specifically 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine) methyl-substituted on N-2. Closely related to (and now mostly superseded by) the tetracyclic antidepressant mirtazapinean, it is an atypical antidepressant used in the treatment of depression throughout Europe and elsewhere. | 3.23 | 1 | 0 | dibenzoazepine | adrenergic uptake inhibitor; alpha-adrenergic antagonist; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; geroprotector; H1-receptor antagonist; histamine agonist; sedative; serotonergic antagonist |
| midazolam Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.. midazolam : An imidazobenzodiazepine that is 4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted by a methyl, 2-fluorophenyl and chloro groups at positions 1, 6 and 8, respectively. | 2.08 | 1 | 0 | imidazobenzodiazepine; monofluorobenzenes; organochlorine compound | anticonvulsant; antineoplastic agent; anxiolytic drug; apoptosis inducer; central nervous system depressant; GABAA receptor agonist; general anaesthetic; muscle relaxant; sedative |
| mirtazapine Mirtazapine: A piperazinoazepine tetracyclic compound that enhances the release of NOREPINEPHRINE and SEROTONIN through blockage of presynaptic ALPHA-2 ADRENERGIC RECEPTORS. It also blocks both 5-HT2 and 5-HT3 serotonin receptors and is a potent HISTAMINE H1 RECEPTOR antagonist. It is used for the treatment of depression, and may also be useful for the treatment of anxiety disorders. | 3.23 | 1 | 0 | benzazepine; tetracyclic antidepressant | alpha-adrenergic antagonist; anxiolytic drug; H1-receptor antagonist; histamine antagonist; oneirogen; serotonergic antagonist |
| nalidixic acid [no description available] | 2.08 | 1 | 0 | 1,8-naphthyridine derivative; monocarboxylic acid; quinolone antibiotic | antibacterial drug; antimicrobial agent; DNA synthesis inhibitor |
| nefazodone nefazodone: may be useful as an opiate adjunct | 2.08 | 1 | 0 | aromatic ether; monochlorobenzenes; N-alkylpiperazine; N-arylpiperazine; triazoles | alpha-adrenergic antagonist; analgesic; antidepressant; serotonergic antagonist; serotonin uptake inhibitor |
| nortriptyline Nortriptyline: A metabolite of AMITRIPTYLINE that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions.. nortriptyline : An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(methylamino)propylidene group at position 5. It is an active metabolite of amitriptyline. | 2.08 | 1 | 0 | organic tricyclic compound; secondary amine | adrenergic uptake inhibitor; analgesic; antidepressant; antineoplastic agent; apoptosis inducer; drug metabolite |
| o(6)-benzylguanine O(6)-benzylguanine: a suicide inhibitor of O(6)-methylguanine-DNA methyltransferase activity | 3.56 | 1 | 1 | ||
| omeprazole Omeprazole: A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.. omeprazole : A racemate comprising equimolar amounts of (R)- and (S)-omeprazole.. 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole : A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a [4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl group at position 2 and a methoxy group at position 5. | 2.08 | 1 | 0 | aromatic ether; benzimidazoles; pyridines; sulfoxide | |
| pantoprazole Pantoprazole: 2-pyridinylmethylsulfinylbenzimidazole proton pump inhibitor that is used in the treatment of GASTROESOPHAGEAL REFLUX and PEPTIC ULCER.. pantoprazole : A member of the class of benzimidazoles that is 1H-benzimidazole substituted by a difluoromethoxy group at position 5 and a [(3,4-dimethoxypyridin-2-yl)methyl]sulfinyl group at position 2. | 2.08 | 1 | 0 | aromatic ether; benzimidazoles; organofluorine compound; pyridines; sulfoxide | anti-ulcer drug; EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor; environmental contaminant; xenobiotic |
| papaverine Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.. papaverine : A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum. | 2.21 | 1 | 0 | benzylisoquinoline alkaloid; dimethoxybenzene; isoquinolines | antispasmodic drug; vasodilator agent |
| pentoxifylline [no description available] | 3.51 | 1 | 0 | oxopurine | |
| phenobarbital Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.. phenobarbital : A member of the class of barbiturates, the structure of which is that of barbituric acid substituted at C-5 by ethyl and phenyl groups. | 2.21 | 1 | 0 | barbiturates | anticonvulsant; drug allergen; excitatory amino acid antagonist; sedative |
| pioglitazone Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.. pioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity. | 2.08 | 1 | 0 | aromatic ether; pyridines; thiazolidinediones | antidepressant; cardioprotective agent; EC 2.7.1.33 (pantothenate kinase) inhibitor; EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; geroprotector; hypoglycemic agent; insulin-sensitizing drug; PPARgamma agonist; xenobiotic |
| praziquantel azinox: Russian drug | 2.08 | 1 | 0 | isoquinolines | |
| propafenone Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.. propafenone : An aromatic ketone that is 3-(propylamino)propane-1,2-diol in which the hydrogen of the primary hydroxy group is replaced by a 2-(3-phenylpropanoyl)phenyl group. It is a class 1C antiarrhythmic drug with local anesthetic effects, and is used as the hydrochloride salt in the management of supraventricular and ventricular arrhythmias. | 2.08 | 1 | 0 | aromatic ketone; secondary alcohol; secondary amino compound | anti-arrhythmia drug |
| propofol Propofol: An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.. propofol : A phenol resulting from the formal substitution of the hydrogen at the 2 position of 1,3-diisopropylbenzene by a hydroxy group. | 2.6 | 1 | 0 | phenols | anticonvulsant; antiemetic; intravenous anaesthetic; radical scavenger; sedative |
| propranolol Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3. | 2.08 | 1 | 0 | naphthalenes; propanolamine; secondary amine | anti-arrhythmia drug; antihypertensive agent; anxiolytic drug; beta-adrenergic antagonist; environmental contaminant; human blood serum metabolite; vasodilator agent; xenobiotic |
| quetiapine [no description available] | 2.08 | 1 | 0 | dibenzothiazepine; N-alkylpiperazine; N-arylpiperazine | adrenergic antagonist; dopaminergic antagonist; histamine antagonist; second generation antipsychotic; serotonergic antagonist |
| risperidone Risperidone: A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.. risperidone : A member of the class of pyridopyrimidines that is 2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one carrying an additional 2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl group at position 2. | 2.08 | 1 | 0 | 1,2-benzoxazoles; heteroarylpiperidine; organofluorine compound; pyridopyrimidine | alpha-adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; H1-receptor antagonist; psychotropic drug; second generation antipsychotic; serotonergic antagonist |
| rolipram [no description available] | 6.01 | 7 | 0 | pyrrolidin-2-ones | antidepressant; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor |
| saccharin Saccharin: Flavoring agent and non-nutritive sweetener.. saccharin : A 1,2-benzisothiazole having a keto-group at the 3-position and two oxo substituents at the 1-position. It is used as an artificial sweetening agent. | 2.17 | 1 | 0 | 1,2-benzisothiazole; N-sulfonylcarboxamide | environmental contaminant; sweetening agent; xenobiotic |
| sulfasalazine Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907). sulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position. | 4.78 | 3 | 0 | ||
| terfenadine Terfenadine: A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME. | 2.08 | 1 | 0 | diarylmethane | |
| thalidomide Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group. | 23.81 | 567 | 99 | phthalimides; piperidones | |
| ultram 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol : A tertiary alcohol that is cyclohexanol substituted at positions 1 and 2 by 3-methoxyphenyl and dimethylaminomethyl groups respectively. | 2.08 | 1 | 0 | aromatic ether; tertiary alcohol; tertiary amino compound | |
| venlafaxine venlafaxine : A tertiary amino compound that is N,N-dimethylethanamine substituted at position 1 by a 1-hydroxycyclohexyl and 4-methoxyphenyl group. | 2.08 | 1 | 0 | cyclohexanols; monomethoxybenzene; tertiary alcohol; tertiary amino compound | adrenergic uptake inhibitor; analgesic; antidepressant; dopamine uptake inhibitor; environmental contaminant; serotonin uptake inhibitor; xenobiotic |
| zardaverine zardaverine: structure given in first source. zardaverine : A pyridazinone derivative in which pyridazin-3(2H)-one is substituted at C-6 with a 4-(difluoromethoxy)-3-methoxyphenyl group. It is a phosphodiesterase inhibitor, selective for PDE3 and 4. | 3.35 | 1 | 0 | organofluorine compound; pyridazinone | anti-asthmatic drug; bronchodilator agent; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; peripheral nervous system drug |
| zinc chloride zinc chloride: RN given refers to parent cpd. zinc dichloride : A compound of zinc and chloride ions in the ratio 1:2. It exists in four crystalline forms, in each of which the Zn(2+) ions are trigonal planar coordinated to four chloride ions. | 3.56 | 1 | 1 | inorganic chloride; zinc molecular entity | astringent; disinfectant; EC 5.3.3.5 (cholestenol Delta-isomerase) inhibitor; Lewis acid |
| prednisolone Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.. prednisolone : A glucocorticoid that is prednisone in which the oxo group at position 11 has been reduced to the corresponding beta-hydroxy group. It is a drug metabolite of prednisone. | 2.66 | 2 | 0 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | adrenergic agent; anti-inflammatory drug; antineoplastic agent; drug metabolite; environmental contaminant; immunosuppressive agent; xenobiotic |
| prednisone Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. prednisone : A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead of the oxo group at position 11), which is the active drug and also a steroid. | 7.66 | 2 | 0 | 11-oxo steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | adrenergic agent; anti-inflammatory drug; antineoplastic agent; immunosuppressive agent; prodrug |
| sucrose Saccharum: A plant genus of the family POACEAE widely cultivated in the tropics for the sweet cane that is processed into sugar. | 3.97 | 2 | 1 | glycosyl glycoside | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; osmolyte; Saccharomyces cerevisiae metabolite; sweetening agent |
| colchicine (S)-colchicine : A colchicine that has (S)-configuration. It is a secondary metabolite, has anti-inflammatory properties and is used to treat gout, crystal-induced joint inflammation, familial Mediterranean fever, and many other conditions. | 2.69 | 2 | 0 | alkaloid; colchicine | anti-inflammatory agent; gout suppressant; mutagen |
| cytarabine [no description available] | 2.21 | 1 | 0 | beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside | antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent |
| boranes Boranes: The collective name for the boron hydrides, which are analogous to the alkanes and silanes. Numerous boranes are known. Some have high calorific values and are used in high-energy fuels. (From Grant & Hackh's Chemical Dictionary, 5th ed). borane : The simplest borane, consisting of a single boron atom carrying three hydrogens.. boranes : The molecular hydrides of boron. | 3.56 | 1 | 1 | boranes; mononuclear parent hydride | |
| n-vinyl-2-pyrrolidinone N-vinyl-2-pyrrolidinone: monomer of POVIDONE; structure given in first source | 2.31 | 1 | 0 | pyrrolidin-2-ones | |
| quinoxalines quinoxaline : A naphthyridine in which the nitrogens are at positions 1 and 4. | 2.1 | 1 | 0 | mancude organic heterobicyclic parent; naphthyridine; ortho-fused heteroarene | |
| furaldehyde Furaldehyde: A heterocyclic compound consisting of a furan where the hydrogen at position 2 is substituted by a formyl group.. furfural : An aldehyde that is furan with the hydrogen at position 2 substituted by a formyl group. | 3.56 | 1 | 1 | aldehyde; furans | Maillard reaction product; metabolite |
| quinuclidines Quinuclidines: A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms and contains an amine group. | 2.51 | 2 | 0 | quinuclidines; saturated organic heterobicyclic parent | |
| pyrroles 1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen. | 7.63 | 17 | 0 | pyrrole; secondary amine | |
| quinazolines Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives. | 3.31 | 1 | 0 | azaarene; mancude organic heterobicyclic parent; ortho-fused heteroarene; quinazolines | |
| adamantane Adamantane: A tricyclo bridged hydrocarbon. | 4.15 | 2 | 0 | adamantanes; polycyclic alkane | |
| isoxazoles Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.. isoxazole : A monocyclic heteroarene with a structure consisting of a 5-membered ring containing three carbon atoms and an oxygen and nitrogen atom adjacent to each other. It is the parent of the class of isoxazoles.. isoxazoles : Oxazoles in which the N and O atoms are adjacent. | 3.21 | 1 | 0 | isoxazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene | |
| thiazoles [no description available] | 5.26 | 4 | 0 | 1,3-thiazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene | |
| betamethasone Betamethasone: A glucocorticoid given orally, parenterally, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p724) | 6.79 | 8 | 2 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(1),Delta(4)-steroid; fluorinated steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | anti-asthmatic agent; anti-inflammatory drug; immunosuppressive agent |
| alpha-aminopyridine alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups. | 5.58 | 6 | 0 | ||
| malondialdehyde Malondialdehyde: The dialdehyde of malonic acid.. malonaldehyde : A dialdehyde that is propane substituted by two oxo groups at the terminal carbon atoms respectively. A biomarker of oxidative damage to lipids caused by smoking, it exists in vivo mainly in the enol form. | 2.17 | 1 | 0 | dialdehyde | biomarker |
| d-alpha tocopherol Vitamin E: A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.. tocopherol : A collective name for a group of closely related lipids that contain a chroman-6-ol nucleus substituted at position 2 by a methyl group and by a saturated hydrocarbon chain consisting of three isoprenoid units. They are designated as alpha-, beta-, gamma-, and delta-tocopherol depending on the number and position of additional methyl substituents on the aromatic ring. Tocopherols occur in vegetable oils and vegetable oil products, almost exclusively with R,R,R configuration. Tocotrienols differ from tocopherols only in having three double bonds in the hydrocarbon chain.. vitamin E : Any member of a group of fat-soluble chromanols that exhibit biological activity against vitamin E deficiency. The vitamers in this class consists of a chroman-6-ol core which is substituted at position 2 by a methyl group and (also at position 2) either a saturated or a triply-unsaturated hydrocarbon chain consisting of three isoprenoid units. The major function of vitamin E is to act as a natural antioxidant by scavenging free radicals and molecular oxygen.. (R,R,R)-alpha-tocopherol : An alpha-tocopherol that has R,R,R configuration. The naturally occurring stereoisomer of alpha-tocopherol, it is found particularly in sunflower and olive oils. | 2.31 | 1 | 0 | alpha-tocopherol | algal metabolite; antiatherogenic agent; anticoagulant; antioxidant; antiviral agent; EC 2.7.11.13 (protein kinase C) inhibitor; immunomodulator; micronutrient; nutraceutical; plant metabolite |
| 7-hydroxychlorpromazine 7-hydroxychlorpromazine: RN given refers to parent cpd | 2.08 | 1 | 0 | phenothiazines | |
| mannose mannopyranose : The pyranose form of mannose. | 2.41 | 1 | 0 | D-aldohexose; D-mannose; mannopyranose | metabolite |
| titanium Titanium: A dark-gray, metallic element of widespread distribution but occurring in small amounts with atomic number, 22, atomic weight, 47.867 and symbol, Ti; specific gravity, 4.5; used for fixation of fractures. | 3.56 | 1 | 1 | titanium group element atom | |
| chromium Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens.. chromium ion : An chromium atom having a net electric charge.. chromium atom : A chromium group element atom that has atomic number 24. | 3.56 | 1 | 1 | chromium group element atom; metal allergen | micronutrient |
| erbium Erbium: Erbium. An element of the rare earth family of metals. It has the atomic symbol Er, atomic number 68, and atomic weight 167.26. | 3.56 | 1 | 1 | f-block element atom; lanthanoid atom | |
| ytterbium Ytterbium: An element of the rare earth family of metals. It has the atomic symbol Yb, atomic number 70, and atomic weight 173. Ytterbium has been used in lasers and as a portable x-ray source. | 3.56 | 1 | 1 | f-block element atom; lanthanoid atom | |
| yttrium Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. | 3.56 | 1 | 1 | d-block element atom; rare earth metal atom; scandium group element atom | |
| fluorides [no description available] | 3.56 | 1 | 1 | halide anion; monoatomic fluorine | |
| chromium chromium hexavalent ion: a human respiratory carcinogen | 3.56 | 1 | 1 | chromium cation; monoatomic hexacation | |
| diltiazem Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.. diltiazem : A 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate in which both stereocentres have S configuration. A calcium-channel blocker and vasodilator, it is used as the hydrochloride in the management of angina pectoris and hypertension. | 2.08 | 1 | 0 | 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate | antihypertensive agent; calcium channel blocker; vasodilator agent |
| paroxetine Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression.. paroxetine : A benzodioxole that consists of piperidine bearing 1,3-benzodioxol-5-yloxy)methyl and 4-fluorophenyl substituents at positions 3 and 4 respectively; the (3S,4R)-diastereomer. Highly potent and selective 5-HT uptake inhibitor that binds with high affinity to the serotonin transporter (Ki = 0.05 nM). Ki values are 1.1, 350 and 1100 nM for inhibition of [3H]-5-HT, [3H]-l-NA and [3H]-DA uptake respectively. Displays minimal affinity for alpha1-, alpha2- or beta-adrenoceptors, 5-HT2A, 5-HT1A, D2 or H1 receptors at concentrations below 1000 nM, however displays weak affinity for muscarinic ACh receptors (Ki = 42 nM). Antidepressant and anxiolytic in vivo. | 3.61 | 2 | 0 | aromatic ether; benzodioxoles; organofluorine compound; piperidines | antidepressant; anxiolytic drug; hepatotoxic agent; P450 inhibitor; serotonin uptake inhibitor |
| encainide Encainide: One of the ANTI-ARRHYTHMIA AGENTS, it blocks VOLTAGE-GATED SODIUM CHANNELS and slows conduction within the His-Purkinje system and MYOCARDIUM.. encainide : 4-Methoxy-N-phenylbenzamide in which the hydrogen at the 2 position of the phenyl group is substituted by a 2-(1-methylpiperidin-2-yl)ethyl group. A class Ic antiarrhythmic, the hydrochloride was used for the treatment of severe or life-threatening ventricular arrhythmias, but it was associated with increased death rates in patients who had asymptomatic heart rhythm abnormalities after a recent heart attack and was withdrawn from the market. | 2.08 | 1 | 0 | benzamides; piperidines | anti-arrhythmia drug; sodium channel blocker |
| atomoxetine atomoxetine : A secondary amino compound having methyl and 3-(2-methylphenoxy)-3-phenylpropan-1-yl substituents. | 2.08 | 1 | 0 | aromatic ether; secondary amino compound; toluenes | adrenergic uptake inhibitor; antidepressant; environmental contaminant; xenobiotic |
| ranolazine Ranolazine: An acetanilide and piperazine derivative that functions as a SODIUM CHANNEL BLOCKER and prevents the release of enzymes during MYOCARDIAL ISCHEMIA. It is used in the treatment of ANGINA PECTORIS.. N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide : An aromatic amide obtained by formal condensation of the carboxy group of 2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetic acid with the amino group of 2,6-dimethylaniline.. ranolazine : A racemate comprising equal amounts of (R)- and (S)-ranolazine. Used for treatment of chronic angina. | 2.08 | 1 | 0 | aromatic amide; monocarboxylic acid amide; monomethoxybenzene; N-alkylpiperazine; secondary alcohol | |
| imiquimod Imiquimod: A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial CARCINOMA, BASAL CELL; and ACTINIC KERATOSIS.. imiquimod : An imidazoquinoline fused [4,5-c] carrying isobutyl and amino substituents at N-1 and C-4 respectively. A prescription medication, it acts as an immune response modifier and is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. | 2.76 | 2 | 0 | imidazoquinoline | antineoplastic agent; interferon inducer |
| adapalene Adapalene: A naphthalene derivative that has specificity for RETINOIC ACID RECEPTORS. It is used as a DERMATOLOGIC AGENT for the treatment of ACNE.. adapalene : A naphthoic acid that is CD437 in which the phenolic hydroxy group has been converted to its methyl ether. | 3.04 | 1 | 0 | adamantanes; monocarboxylic acid; naphthoic acid | dermatologic drug; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor; non-steroidal anti-inflammatory drug |
| atorvastatin [no description available] | 2.08 | 1 | 0 | aromatic amide; dihydroxy monocarboxylic acid; monofluorobenzenes; pyrroles; statin (synthetic) | environmental contaminant; xenobiotic |
| duloxetine [no description available] | 2.08 | 1 | 0 | duloxetine | |
| adenosine quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit | 3.62 | 2 | 0 | adenosines; purines D-ribonucleoside | analgesic; anti-arrhythmia drug; fundamental metabolite; human metabolite; vasodilator agent |
| efavirenz efavirenz: HIV-1 reverse transcriptase inhibitor. efavirenz : 1,4-Dihydro-2H-3,1-benzoxazin-2-one substituted at the 4 position by cyclopropylethynyl and trifluoromethyl groups (S configuration) and at the 6 position by chlorine. A non-nucleoside reverse transcriptase inhibitor with activity against HIV, it is used with other antiretrovirals for combination therapy of HIV infection. | 2.08 | 1 | 0 | acetylenic compound; benzoxazine; cyclopropanes; organochlorine compound; organofluorine compound | antiviral drug; HIV-1 reverse transcriptase inhibitor |
| nelfinavir Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.. nelfinavir : An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties. | 2.08 | 1 | 0 | aryl sulfide; benzamides; organic heterobicyclic compound; phenols; secondary alcohol; tertiary amino compound | antineoplastic agent; HIV protease inhibitor |
| glucose, (beta-d)-isomer beta-D-glucose : D-Glucopyranose with beta configuration at the anomeric centre.. (1->4)-beta-D-glucan : A beta-D-glucan in which the glucose units are connected by (1->4) linkages.. (1->3)-beta-D-glucan : A beta-D-glucan in which the glucose units are connected by (1->3) linkages. | 4.38 | 4 | 0 | D-glucopyranose | epitope; mouse metabolite |
| betulinic acid [no description available] | 2.25 | 1 | 0 | hydroxy monocarboxylic acid; pentacyclic triterpenoid | anti-HIV agent; anti-inflammatory agent; antimalarial; antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; plant metabolite |
| repaglinide [no description available] | 2.08 | 1 | 0 | piperidines | |
| triazoles Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms. | 2.1 | 1 | 0 | 1,2,3-triazole | |
| fluorodeoxyglucose f18 Fluorodeoxyglucose F18: The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162) | 5.52 | 2 | 2 | 2-deoxy-2-((18)F)fluoro-D-glucose; 2-deoxy-2-fluoro-aldehydo-D-glucose | |
| tocophersolan tocophersolan: RN given refers to parent cpd | 2.31 | 1 | 0 | tocol | |
| bufuralol bufuralol: RN given refers to cpd without isomeric designation; structure | 2.08 | 1 | 0 | benzofurans | |
| rosiglitazone [no description available] | 2.08 | 1 | 0 | aminopyridine; thiazolidinediones | EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; insulin-sensitizing drug |
| clarithromycin Clarithromycin: A semisynthetic macrolide antibiotic derived from ERYTHROMYCIN that is active against a variety of microorganisms. It can inhibit PROTEIN SYNTHESIS in BACTERIA by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation.. clarithromycin : The 6-O-methyl ether of erythromycin A, clarithromycin is a macrolide antibiotic used in the treatment of respiratory-tract, skin and soft-tissue infections. It is also used to eradicate Helicobacter pylori in the treatment of peptic ulcer disease. It prevents bacteria from growing by interfering with their protein synthesis. | 2.08 | 1 | 0 | macrolide antibiotic | antibacterial drug; environmental contaminant; protein synthesis inhibitor; xenobiotic |
| 4-hydroxypropranolol 4-hydroxypropranolol: metabolite of propanolol; RN given refers to parent cpd without isomeric designation | 2.08 | 1 | 0 | naphthols | |
| yttrium radioisotopes Yttrium Radioisotopes: Unstable isotopes of yttrium that decay or disintegrate emitting radiation. Y atoms with atomic weights 82-88 and 90-96 are radioactive yttrium isotopes. | 3.56 | 1 | 1 | ||
| bosentan anhydrous Bosentan: A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS. | 2.08 | 1 | 0 | primary alcohol; pyrimidines; sulfonamide | antihypertensive agent; endothelin receptor antagonist |
| n-monodemethyldiltiazem N-monodemethyldiltiazem: RN given refers to (cis)-isomer; structure given in first source | 2.08 | 1 | 0 | benzothiazepine | |
| fingolimod fingolimod : An aminodiol that consists of propane-1,3-diol having amino and 2-(4-octylphenyl)ethyl substituents at the 2-position. It is a sphingosine 1-phosphate receptor modulator used for the treatment of relapsing-remitting multiple sclerosis. A prodrug, fingolimod is phosphorylated by sphingosine kinase to active metabolite fingolimod-phosphate, a structural analogue of sphingosine 1-phosphate. | 2.21 | 1 | 0 | aminodiol; primary amino compound | antineoplastic agent; CB1 receptor antagonist; immunosuppressive agent; prodrug; sphingosine-1-phosphate receptor agonist |
| tadalafil [no description available] | 2.08 | 1 | 0 | benzodioxoles; pyrazinopyridoindole | EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor; vasodilator agent |
| valdecoxib [no description available] | 2.08 | 1 | 0 | isoxazoles; sulfonamide | antipyretic; antirheumatic drug; cyclooxygenase 2 inhibitor; non-narcotic analgesic; non-steroidal anti-inflammatory drug |
| gefitinib [no description available] | 2.08 | 1 | 0 | aromatic ether; monochlorobenzenes; monofluorobenzenes; morpholines; quinazolines; secondary amino compound; tertiary amino compound | antineoplastic agent; epidermal growth factor receptor antagonist |
| n(6)-(3-iodobenzyl)-5'-n-methylcarboxamidoadenosine N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine: structure given in first source; a selective A(3) adenosine receptor agonist. 3-iodobenzyl-5'-N-methylcarboxamidoadenosine : A derivative of adenosine in which the 5'-hydroxymethyl group is replaced by N-ethylcarboxamido and one of the hydrogens of the exocyclic amino function is substituted by a 3-iodobenzyl group. | 3.23 | 1 | 0 | adenosines; monocarboxylic acid amide; organoiodine compound | adenosine A3 receptor agonist |
| desloratadine desloratadine: major metabolite of loratadine. desloratadine : Loratadine in which the ethoxycarbonyl group attached to the piperidine ring is replaced by hydrogen. The major metabolite of loratidine, desloratadine is an antihistamine which is used for the symptomatic relief of allergic conditions including rhinitis and chronic urticaria. It does not readily enter the central nervous system, so does not cause drowsiness. | 2.08 | 1 | 0 | benzocycloheptapyridine | anti-allergic agent; cholinergic antagonist; drug metabolite; H1-receptor antagonist |
| methotrexate [no description available] | 12.79 | 36 | 5 | dicarboxylic acid; monocarboxylic acid amide; pteridines | abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent |
| pagoclone RP 59037: a partial benzodiazepine receptor agonist; a cyclopyrrolone that induces hypothermia | 2.08 | 1 | 0 | ||
| pomalidomide 3-aminophthalimidoglutarimide: structure in first source | 2.31 | 1 | 0 | aromatic amine; dicarboximide; isoindoles; piperidones | angiogenesis inhibitor; antineoplastic agent; immunomodulator |
| betamethasone-17,21-dipropionate betamethasone-17,21-dipropionate: may also contain chlorocresol (UD 25:22R) | 6.7 | 7 | 2 | ||
| cilomilast [no description available] | 4.65 | 2 | 0 | methoxybenzenes | |
| bazedoxifene [no description available] | 2.11 | 1 | 0 | phenylindole | |
| rp 73401 piclamilast: an antiasthmatic agent and phosphodiesterase 4 inhibitor; structure in first source. piclamilast : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 3-(cyclopentyloxy)-4-methoxybenzoic acid with the primary amino group of 3,5-dichloropyridin-4-amine. | 3.35 | 1 | 0 | aromatic ether; benzamides; chloropyridine; monocarboxylic acid amide | anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; phosphodiesterase IV inhibitor |
| erlotinib [no description available] | 2.08 | 1 | 0 | aromatic ether; quinazolines; secondary amino compound; terminal acetylenic compound | antineoplastic agent; epidermal growth factor receptor antagonist; protein kinase inhibitor |
| eslicarbazepine acetate eslicarbazepine acetate : The acetate ester, with S configuration, of licarbazepine. An anticonvulsant, it is approved for use in Europe and the United States as an adjunctive therapy for epilepsy. | 2.11 | 1 | 0 | acetate ester; carboxamide; dibenzoazepine; ureas | anticonvulsant; drug allergen |
| mesembrenone mesembrenone: a psychoactive compound isolated from Sceletium tortuosum; structure in first source | 3.35 | 1 | 0 | pyrrolidines | |
| 5-hydroxymethylfurfural 5-hydroxymethylfurfural: has antisickling activity; HMF is the causative component in honey that affects the presystemic metabolism and pharmacokinetics of GZ in-vivo. 5-hydroxymethylfurfural : A member of the class of furans that is furan which is substituted at positions 2 and 5 by formyl and hydroxymethyl substituents, respectively. Virtually absent from fresh foods, it is naturally generated in sugar-containing foods during storage, and especially by drying or cooking. It is the causative component in honey that affects the presystemic metabolism and pharmacokinetics of GZ in-vivo. | 3.56 | 1 | 1 | arenecarbaldehyde; furans; primary alcohol | indicator; Maillard reaction product |
| glucosamine D-glucosamine : An amino sugar whose structure comprises D-glucose having an amino substituent at position 2.. 2-amino-2-deoxy-D-glucopyranose : A D-glucosamine whose structure comprises D-glucopyranose having an amino substituent at position 2. | 2.21 | 1 | 0 | D-glucosamine | Escherichia coli metabolite; geroprotector; mouse metabolite |
| carnosine polaprezinc: stimulates bone growth | 2.21 | 1 | 0 | amino acid zwitterion; dipeptide | anticonvulsant; antineoplastic agent; antioxidant; Daphnia magna metabolite; geroprotector; human metabolite; mouse metabolite; neuroprotective agent |
| quinidine Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.. quinidine : A cinchona alkaloid consisting of cinchonine with the hydrogen at the 6-position of the quinoline ring substituted by methoxy. | 2.08 | 1 | 0 | cinchona alkaloid | alpha-adrenergic antagonist; anti-arrhythmia drug; antimalarial; drug allergen; EC 1.14.13.181 (13-deoxydaunorubicin hydroxylase) inhibitor; EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor; muscarinic antagonist; P450 inhibitor; potassium channel blocker; sodium channel blocker |
| tolterodine [no description available] | 2.08 | 1 | 0 | tertiary amine | antispasmodic drug; muscarinic antagonist; muscle relaxant |
| tibolone tibolone: used in prevention of postmenopausal osteoporosis. tibolone : Estran-3-one with a double bond between positions 5 and 10, and bearing both an ethynyl group and a hydroxy group at position 17 (R-configuration). A synthetic steroid hormone drug which acts as an agonist at all five type I steroid hormone receptors, it is used in the prevention of postmenopausal osteoporosis and for treatment of endometriosis. | 2.08 | 1 | 0 | 17beta-hydroxy steroid; terminal acetylenic compound | bone density conservation agent; hormone agonist |
| darifenacin darifenacin : 2-[(3S)-1-Ethylpyrrolidin-3-yl]-2,2-diphenylacetamide in which one of the hydrogens at the 2-position of the ethyl group is substituted by a 2,3-dihydro-1-benzofuran-5-yl group. It is a selective antagonist for the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions, and is used as the hydrobromide salt in the management of urinary incontinence. | 2.08 | 1 | 0 | 1-benzofurans; monocarboxylic acid amide; pyrrolidines | antispasmodic drug; muscarinic antagonist |
| fumaric acid fumaric acid: see also record for ferrous fumarate; use FUMARATES for general fumaric acid esters. fumaric acid : A butenedioic acid in which the C=C double bond has E geometry. It is an intermediate metabolite in the citric acid cycle. | 7.69 | 2 | 0 | butenedioic acid | food acidity regulator; fundamental metabolite; geroprotector |
| cerivastatin cerivastatin: cerivastatin is the ((E)-(+))-isomer; structure given in first source. cerivastatin : (3R,5S)-3,5-dihydroxyhept-6-enoic acid in which the (7E)-hydrogen is substituted by a 4-(4-fluorophenyl)-2,6-diisopropyl-5-(methoxymethyl)pyridin-3-yl group. Formerly used (as its sodium salt) to lower cholesterol and prevent cardiovascular disease, it was withdrawn from the market worldwide in 2001 following reports of a severe form of muscle toxicity. | 2.08 | 1 | 0 | dihydroxy monocarboxylic acid; pyridines; statin (synthetic) | |
| mycophenolic acid Mycophenolic Acid: Compound derived from Penicillium stoloniferum and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase (IMP DEHYDROGENASE). Mycophenolic acid exerts selective effects on the immune system in which it prevents the proliferation of T-CELLS, LYMPHOCYTES, and the formation of antibodies from B-CELLS. It may also inhibit recruitment of LEUKOCYTES to sites of INFLAMMATION.. mycophenolate : A monocarboxylic acid anion resulting from the removal of a proton from the carboxy group of mycophenolic acid.. mycophenolic acid : A member of the class of 2-benzofurans that is 2-benzofuran-1(3H)-one which is substituted at positions 4, 5, 6, and 7 by methyl, methoxy, (2E)-5-carboxy-3-methylpent-2-en-1-yl, and hydroxy groups, respectively. It is an antibiotic produced by Penicillium brevi-compactum, P. stoloniferum, P. echinulatum and related species. An immunosuppressant, it is widely used (partiularly as its sodium salt and as the 2-(morpholin-4-yl)ethyl ester prodrug, mycophenolate mofetil) to prevent tissue rejection following organ transplants and for the treatment of certain autoimmune diseases. | 4.64 | 4 | 0 | 2-benzofurans; gamma-lactone; monocarboxylic acid; phenols | anticoronaviral agent; antimicrobial agent; antineoplastic agent; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; environmental contaminant; immunosuppressive agent; mycotoxin; Penicillium metabolite; xenobiotic |
| rolipram (-)-rolipram : The (R)-enantiomer of rolipram. | 2.21 | 1 | 0 | rolipram | |
| roflumilast [no description available] | 7.14 | 12 | 0 | aromatic ether; benzamides; chloropyridine; cyclopropanes; organofluorine compound | anti-asthmatic drug; phosphodiesterase IV inhibitor |
| efinaconazole efinaconazole: an antifungal agent; structure in first source. efinaconazole : A member of the class of triazoles that is butan-2-ol which is substituted at positions 1, 2, and 3 by 1,2,4-triazol-1-yl, 2,4-difluorophenyl, and 4-methylenepiperidin-1-yl groups, respectively (the 2R,3R stereoisomer). It is an antifungal drug used for the topical treatment of onychomycosis (a nail infection caused mainly by dermatophytes). | 2.1 | 1 | 0 | conazole antifungal drug; olefinic compound; organofluorine compound; piperidines; tertiary alcohol; tertiary amino compound; triazole antifungal drug | EC 1.14.13.70 (sterol 14alpha-demethylase) inhibitor |
| bromochloroacetic acid Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.. bromochloroacetic acid : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by bromine while a second is replaced by chlorine. A low-melting (27.5-31.5degreeC), hygroscopic crystalline solid, it can be formed during the disinfection (by chlorination) of water that contains bromide ions and organic matter, so can occur in drinking water as a byproduct of the disinfection process. | 2.6 | 1 | 0 | 2-bromocarboxylic acid; monocarboxylic acid; organochlorine compound | |
| thioguanine anhydrous Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.. tioguanine : A 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine. Incorporates into DNA and inhibits synthesis. Used in the treatment of leukaemia. | 3.21 | 1 | 0 | 2-aminopurines | anticoronaviral agent; antimetabolite; antineoplastic agent |
| meso-1,2-diphenylethylenediamine, (r-(r*,s*))-isomer diphenylethylenediamine: structure in first source | 3.56 | 1 | 1 | ||
| tamoxifen [no description available] | 2.08 | 1 | 0 | stilbenoid; tertiary amino compound | angiogenesis inhibitor; antineoplastic agent; bone density conservation agent; EC 1.2.3.1 (aldehyde oxidase) inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; estrogen antagonist; estrogen receptor antagonist; estrogen receptor modulator |
| 3-(n,n-dimethylsulfonamido)-4-methyl-nitrobenzene BRL-50481 : A C-nitro compound that is benzene substituted by N,N-dimethylaminosulfonyl, methyl and nitro groups at positions 1, 2 and 5, respectively. It is a phosphodiesterase inhibitor selective for the PDE7 subtype (Ki = 180 nM). | 2.21 | 1 | 0 | C-nitro compound; sulfonamide; toluenes | bone density conservation agent; EC 3.1.4.53 (3',5'-cyclic-AMP phosphodiesterase) inhibitor; geroprotector |
| tetomilast [no description available] | 4.81 | 3 | 0 | ||
| dolasetron [no description available] | 2.08 | 1 | 0 | indolyl carboxylic acid | |
| 2-(4-(2-carboxyethyl)phenethylamino)-5'-n-ethylcarboxamidoadenosine 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine: A2 adenosine receptor agonist; structure given in first source. CGS-21680 : A derivative of adenosine in which the 5'-hydroxymethyl group is replaced by N-ethylcarboxamido and the hydrogen at position 2 on the adenine is replaced by a 4-(2-carboxyethyl)phenethylamino group. | 2.11 | 1 | 0 | adenosines; dicarboxylic acid monoamide; monocarboxylic acid | adenosine A2A receptor agonist; anti-inflammatory agent |
| 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione: a GSK3beta inhibitor. TDZD-8 : A member of the class of thiadiazolidines that is 1,2,4-thiadiazolidine-3,5-dione which is substituted by a methyl group at position 2 and by a benzyl group at position 4. It is a non-ATP competitive inhibitor of glycogen synthase kinase 3beta (GSK3beta). An experimental compound which was being developed for the potential treatment of Alzheimer's disease. | 3.56 | 1 | 1 | benzenes; thiadiazolidine | anti-inflammatory agent; antineoplastic agent; apoptosis inducer; EC 2.7.11.26 (tau-protein kinase) inhibitor; neuroprotective agent |
| osteoprotegerin Osteoprotegerin: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B. | 4.39 | 1 | 1 | long-chain fatty acid | |
| calcitriol dihydroxy-vitamin D3: as a major in vitro metabolite of 1alpha,25-dihydroxyvitamin D3, produced in primary cultures of neonatal human keratinocytes | 6.67 | 7 | 2 | D3 vitamins; hydroxycalciol; triol | antineoplastic agent; antipsoriatic; bone density conservation agent; calcium channel agonist; calcium channel modulator; hormone; human metabolite; immunomodulator; metabolite; mouse metabolite; nutraceutical |
| montelukast montelukast: a leukotriene D4 receptor antagonist | 2.08 | 1 | 0 | aliphatic sulfide; monocarboxylic acid; quinolines | anti-arrhythmia drug; anti-asthmatic drug; leukotriene antagonist |
| mangostin mangostin: xanthone from rind of Garcinia mangostana Linn. fruit. alpha-mangostin : A member of the class of xanthones that is 9H-xanthene substituted by hydroxy group at positions 1, 3 and 6, a methoxy group at position 7, an oxo group at position 9 and prenyl groups at positions 2 and 8. Isolated from the stems of Cratoxylum cochinchinense, it exhibits antioxidant, antimicrobial and antitumour activities. | 2.25 | 1 | 0 | aromatic ether; phenols; xanthones | antimicrobial agent; antineoplastic agent; antioxidant; plant metabolite |
| coenzyme q10 coenzyme Q10: Ubiquinone ring with a chain of 10 isoprene units; redox equilibrium with ubiqunol serving in mitochondrial inner membrane to transfer electrons; presence during reconstitution of acetylcholine receptor into phospholipid vesicles yields vesicles active in catalyzing carbamylcholine-sensitive Na+ flux; coenzyme Q10 depletion has been noted with use of statins. coenzyme Q10 : A ubiquinone having a side chain of 10 isoprenoid units. In the naturally occurring isomer, all isoprenyl double bonds are in the E- configuration. | 3.56 | 1 | 1 | ubiquinones | antioxidant; ferroptosis inhibitor; human metabolite |
| etretinate retinoid : Oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof. | 2.6 | 1 | 0 | enoate ester; ethyl ester; retinoid | keratolytic drug |
| isotretinoin Isotretinoin: A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.. isotretinoin : A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases. | 7.41 | 1 | 0 | retinoic acid | antineoplastic agent; keratolytic drug; teratogenic agent |
| ubiquinone 8 [no description available] | 3.56 | 1 | 1 | ubiquinones | biomarker |
| menaquinone 6 menaquinone 6: RN given refers to (all-E)-isomer | 3.56 | 1 | 1 | ||
| codeine [no description available] | 2.08 | 1 | 0 | morphinane alkaloid; organic heteropentacyclic compound | antitussive; drug allergen; environmental contaminant; opioid analgesic; opioid receptor agonist; prodrug; xenobiotic |
| acitretin Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate.. acitretin : A retinoid that consists of 3,7-dimethylnona-2,4,6,8-tetraenoic acid having a 4-methoxy-2,3,6-trimethylphenyl group attached at position 9. | 10.74 | 9 | 0 | acitretin; alpha,beta-unsaturated monocarboxylic acid; retinoid | keratolytic drug |
| menaquinone 7 menaquinone-7 : A menaquinone whose side-chain contains seven isoprene units in an all-trans-configutation. | 3.56 | 1 | 1 | menaquinone | bone density conservation agent; cofactor; Escherichia coli metabolite; human blood serum metabolite; Mycoplasma genitalium metabolite |
| 4-amino-5-chloro-N-[(3R,4S)-1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide [no description available] | 3.12 | 1 | 0 | benzamides | |
| clobetasol Clobetasol: A derivative of PREDNISOLONE with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than FLUOCINONIDE, it is used topically in treatment of PSORIASIS but may cause marked adrenocortical suppression.. clobetasol : A 3-oxo-Delta(1),Delta(4)-steroid that is 16beta-methylpregna-1,4-diene-3,20-dione bearing hydroxy groups at the 11beta and 17alpha positions, fluorine at position 9, and a chlorine substituent at position 21. It is used as its 17alpha-propionate ester to treat various skin disorders, including exzema and psoriasis. | 8.64 | 1 | 1 | 11beta-hydroxy steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 3-oxo-Delta(1),Delta(4)-steroid; chlorinated steroid; fluorinated steroid; glucocorticoid; tertiary alpha-hydroxy ketone | anti-inflammatory drug; SMO receptor agonist |
| strontium Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62. | 3.56 | 1 | 1 | alkaline earth metal atom | |
| naltrexone Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.. naltrexone : An organic heteropentacyclic compound that is naloxone substituted in which the allyl group attached to the nitrogen is replaced by a cyclopropylmethyl group. A mu-opioid receptor antagonist, it is used to treat alcohol dependence. | 2.08 | 1 | 0 | cyclopropanes; morphinane-like compound; organic heteropentacyclic compound | antidote to opioid poisoning; central nervous system depressant; environmental contaminant; mu-opioid receptor antagonist; xenobiotic |
| dextromethorphan Dextromethorphan: Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.. dextromethorphan : A 6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene in which the sterocenters at positions 4a, 10 and 10a have S-configuration. It is a prodrug of dextrorphan and used as an antitussive drug for suppressing cough. | 2.08 | 1 | 0 | 6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene | antitussive; environmental contaminant; neurotoxin; NMDA receptor antagonist; oneirogen; prodrug; xenobiotic |
| fumarates Fumarates: Compounds based on fumaric acid.. fumarate(2-) : A C4-dicarboxylate that is the E-isomer of but-2-enedioate(2-) | 4.16 | 4 | 0 | butenedioate; C4-dicarboxylate | human metabolite; metabolite; Saccharomyces cerevisiae metabolite |
| 9-Hydroxycalabaxanthone [no description available] | 2.25 | 1 | 0 | xanthones | |
| everolimus [no description available] | 7.6 | 1 | 0 | cyclic acetal; cyclic ketone; ether; macrolide lactam; primary alcohol; secondary alcohol | anticoronaviral agent; antineoplastic agent; geroprotector; immunosuppressive agent; mTOR inhibitor |
| indacaterol indacaterol: a beta2 adrenoceptor agonist; indacaterol is the (R)-isomer; structure in first source. indacaterol : A monohydroxyquinoline that consists of 5-[(1R)-2-amino-1-hydroxyethyl]-8-hydroxyquinolin-2-one having a 5,6-diethylindan-2-yl group attached to the amino function. Used as the maleate salt for treatment of chronic obstructive pulmonary disease. | 2.08 | 1 | 0 | indanes; monohydroxyquinoline; quinolone; secondary alcohol; secondary amino compound | beta-adrenergic agonist; bronchodilator agent |
| gsk 256066 [no description available] | 3.71 | 2 | 0 | ||
| mocetinostat mocetinostat: undergoing phase II clinical trials for treatment of cancer. mocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11). | 2.21 | 1 | 0 | aminopyrimidine; benzamides; pyridines; secondary amino compound; secondary carboxamide; substituted aniline | antineoplastic agent; apoptosis inducer; autophagy inducer; cardioprotective agent; EC 3.5.1.98 (histone deacetylase) inhibitor; hepatotoxic agent |
| avanafil [no description available] | 2.11 | 1 | 0 | aromatic amide; monocarboxylic acid amide; organochlorine compound; prolinols; pyrimidines | EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; vasodilator agent |
| ticagrelor Ticagrelor: An adenosine triphosphate analogue and reversible P2Y12 PURINORECEPTOR antagonist that inhibits ADP-mediated PLATELET AGGREGATION. It is used for the prevention of THROMBOEMBOLISM by patients with ACUTE CORONARY SYNDROME or a history of MYOCARDIAL INFARCTION.. ticagrelor : A triazolopyrimidine that is an adenosine isostere; the cyclopentane ring is similar to ribose and the nitrogen-rich [1,2,3]triazolo[4,5-d]pyrimidine moiety resembles the nucleobase adenine. A platelet aggregation inhibitor which is used for prevention of thromboembolic events in patients with acute coronary syndrome. | 2.08 | 1 | 0 | aryl sulfide; hydroxyether; organofluorine compound; secondary amino compound; triazolopyrimidines | P2Y12 receptor antagonist; platelet aggregation inhibitor |
| dapagliflozin [no description available] | 2.51 | 2 | 0 | aromatic ether; C-glycosyl compound; monochlorobenzenes | hypoglycemic agent; sodium-glucose transport protein subtype 2 inhibitor |
| perampanel perampanel : A member of the class of bipyridines that is 2,3'-bipyridin-6'-one substituted at positions 1' and 5' by phenyl and 2-cyanophenyl groups respectively. Used as an adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy. | 2.11 | 1 | 0 | bipyridines; nitrile; pyridone | AMPA receptor antagonist; anticonvulsant |
| tofacitinib tofacitinib : A pyrrolopyrimidine that is pyrrolo[2,3-d]pyrimidine substituted at position 4 by an N-methyl,N-(1-cyanoacetyl-4-methylpiperidin-3-yl)amino moiety. Used as its citrate salt to treat moderately to severely active rheumatoid arthritis. | 9.31 | 21 | 1 | N-acylpiperidine; nitrile; pyrrolopyrimidine; tertiary amino compound | antirheumatic drug; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor |
| rpl 554 ensifentrine: a phosphodiesterase 3/4 inhibitor; structure in first source | 3.35 | 1 | 0 | ||
| vorapaxar vorapaxar: has antiplatelet activity; structure in first source. vorapaxar : A carbamate ester that is the ethyl ester of [(1R,3aR,4aR,6R,8aR,9S,9aS)-9-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]ethynyl}-1-methyl-3-oxododecahydronaphtho[2,3-c]furan-6-yl]carbamic acid. A protease-activated receptor-1 antagonist used (as its sulfate salt) for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease. It has been shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke and urgent coronary revascularisation. | 2.1 | 1 | 0 | carbamate ester; lactone; naphthofuran; organofluorine compound; pyridines | cardiovascular drug; platelet aggregation inhibitor; protease-activated receptor-1 antagonist |
| apixaban [no description available] | 2.08 | 1 | 0 | aromatic ether; lactam; piperidones; pyrazolopyridine | anticoagulant; EC 3.4.21.6 (coagulation factor Xa) inhibitor |
| vilanterol [no description available] | 2.51 | 2 | 0 | benzyl alcohols; dichlorobenzene; ether; phenols; secondary amino compound | beta-adrenergic agonist; bronchodilator agent |
| n-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide: MK-0364 is the (1S,2S)-isomer; a cannabinoid-1 receptor inverse agonist; structure in first source | 2.08 | 1 | 0 | stilbenoid | |
| brimonidine tartrate Brimonidine Tartrate: A quinoxaline derivative and ADRENERGIC ALHPA-2 RECEPTOR AGONIST that is used to manage INTRAOCULAR PRESSURE associated with OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION. | 2.1 | 1 | 0 | ||
| bay 63-2521 riociguat: guanylate cyclase stimulator; structure in first source. riociguat : A carbamate ester that is the methyl ester of {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamic acid. It is used for treatment of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension | 2.1 | 1 | 0 | aminopyrimidine; carbamate ester; organofluorine compound; pyrazolopyridine | antihypertensive agent; soluble guanylate cyclase activator |
| ponesimod ponesimod: structure in first source | 4.16 | 2 | 0 | ||
| oglemilast oglemilast: a PDE4 inhibitor and NSAID; no further info available 1/2006 | 2.13 | 1 | 0 | ||
| tavaborole tavaborole: has antifungal activity; structure in first source. tavaborole : A member of the class of benzoxaboroles that is 1,3-dihydro-1-hydroxy-2,1-benzoxaborole substituted at position 5 by a fluoro group. A topical antifungal agent used for the treatment of onychomycosis (fungal infection of the toenails and fingernails). | 2.1 | 1 | 0 | benzoxaborole; organofluorine compound | antifungal agent; EC 6.1.1.4 (leucine--tRNA ligase) inhibitor; protein synthesis inhibitor |
| gsk573719 GSK573719: Muscarinic Antagonist. umeclidinium : A quaternary ammonium ion that is quinuclidine substituted at positions 1 and 4 by 2-(benzyloxy)ethyl and hydroxy(diphenyl)methyl groups respectively. | 2.51 | 2 | 0 | ||
| carfilzomib [no description available] | 2.57 | 2 | 0 | epoxide; morpholines; tetrapeptide | antineoplastic agent; proteasome inhibitor |
| fostamatinib fostamatinib: a spleen tyrosine kinase (Syk) inhibitor, metabolized to R406 | 3.17 | 1 | 0 | ||
| losartan potassium Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation. | 3.56 | 1 | 1 | ||
| n-acetylmannosamine N-acetylmannosamine: RN given refers to cpd without isomeric designation. N-acetylmannosamine : Any mannosamine carrying an N-acetyl substituent | 3.56 | 1 | 1 | ||
| dextrothyroxine [no description available] | 2.1 | 1 | 0 | ||
| tannins Tannins: Polyphenolic compounds with molecular weights of around 500-3000 daltons and containing enough hydroxyl groups (1-2 per 100 MW) for effective cross linking of other compounds (ASTRINGENTS). The two main types are HYDROLYZABLE TANNINS and CONDENSED TANNINS. Historically, the term has applied to many compounds and plant extracts able to render skin COLLAGEN impervious to degradation. The word tannin derives from the Celtic word for OAK TREE which was used for leather processing. | 3.56 | 1 | 1 | ||
| oligonucleotides [no description available] | 3.35 | 1 | 0 | ||
| glucagon-like peptide 1 Glucagon-Like Peptide 1: A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake. | 2.1 | 1 | 0 | ||
| ubiquinone Ubiquinone: A lipid-soluble benzoquinone which is involved in ELECTRON TRANSPORT in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. | 3.56 | 1 | 1 | ||
| chitosan [no description available] | 2.41 | 1 | 0 | ||
| incb-018424 [no description available] | 3.61 | 2 | 0 | nitrile; pyrazoles; pyrrolopyrimidine | antineoplastic agent; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor |
| glycolipids [no description available] | 3.56 | 1 | 1 | ||
| baricitinib [no description available] | 4.8 | 3 | 0 | azetidines; nitrile; pyrazoles; pyrrolopyrimidine; sulfonamide | anti-inflammatory agent; antirheumatic drug; antiviral agent; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; immunosuppressive agent |
| piperidines Piperidines: A family of hexahydropyridines. | 9.31 | 21 | 1 | ||
| interleukin-8 Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells. | 2.72 | 2 | 0 | ||
| an2728 crisaborole: NSAID, Dermatologic Agent; structure in first source. crisaborole : A member of the class of benzoxaboroles that is 5-hydroxy-1,3-dihydro-2,1-benzoxaborole in which the phenolic hydrogen has been replaced by a 4-cyanophenyl group. A phosphodiesterase 4 inhibitor that is used for treatment of mild to moderate atopic dermatitis in children and adults. | 5.22 | 5 | 0 | aromatic ether; benzoxaborole; nitrile | antipsoriatic; non-steroidal anti-inflammatory drug; phosphodiesterase IV inhibitor |
| gsk525762a molibresib: mimicks acetylated histones; structure in first source | 2.31 | 1 | 0 | benzodiazepine | |
| calcipotriene calcipotriene: a topical dermatologic for the treatment of moderate plaque psoriasis; structure in first source. calcipotriol hydrate : A hydrate that is the monohydrate form of calcipotriol. It is used in combination with betamethasone dipropionate, a corticosteroid, for the topical treatment of plaque psoriasis in adult patients. | 6.67 | 7 | 2 | hydrate | antipsoriatic |
| incb039110 INCB039110: a JAK1 inhibitor; structure in first source | 3.23 | 1 | 0 | ||
| (S)-warfarin (S)-warfarin : A 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one that has (S)-configuration (the racemate is warfarin, an anticoagulant drug and rodenticide). | 2.08 | 1 | 0 | 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one | |
| transforming growth factor beta Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. | 3.35 | 1 | 0 | ||
| d159687 [no description available] | 2.6 | 1 | 0 | ||
| chf6001 tanimilast: a phosphodiesterase-4 inhibitor; structure in first source | 3.35 | 1 | 0 | ||
| ged0301 GED0301: a Smad7 antisense oligonucleotide | 3.35 | 1 | 0 | ||
| cyclosporine Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). | 12.63 | 12 | 1 | ||
| acyclovir Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.. acyclovir : An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections. | 3.27 | 1 | 0 | 2-aminopurines; oxopurine | antimetabolite; antiviral drug |
| guanine [no description available] | 3.56 | 1 | 1 | 2-aminopurines; oxopurine; purine nucleobase | algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| rifampin Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160) | 4.4 | 1 | 1 | cyclic ketal; hydrazone; N-iminopiperazine; N-methylpiperazine; rifamycins; semisynthetic derivative; zwitterion | angiogenesis inhibitor; antiamoebic agent; antineoplastic agent; antitubercular agent; DNA synthesis inhibitor; EC 2.7.7.6 (RNA polymerase) inhibitor; Escherichia coli metabolite; geroprotector; leprostatic drug; neuroprotective agent; pregnane X receptor agonist; protein synthesis inhibitor |
| clozapine Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.. clozapine : A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatric disorders like schizophrenia. | 2.08 | 1 | 0 | benzodiazepine; N-arylpiperazine; N-methylpiperazine; organochlorine compound | adrenergic antagonist; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; environmental contaminant; GABA antagonist; histamine antagonist; muscarinic antagonist; second generation antipsychotic; serotonergic antagonist; xenobiotic |
| norclozapine norclozapine: structure given in first source. N-desmethylclozapine : A dibenzodoazepine substituted with chloro and piperazino groups which is a major metabolite of clozapine; a potent and selective 5-HT2C serotonin receptor antagonist. | 2.08 | 1 | 0 | dibenzodiazepine; organochlorine compound; piperazines | delta-opioid receptor agonist; metabolite; serotonergic antagonist |
| sildenafil citrate Sildenafil Citrate: A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.. sildenafil citrate : The citrate salt of sildenafil. | 3.73 | 2 | 0 | citrate salt | EC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor; vasodilator agent |
| bay 73-6691 BAY 73-6691: potent and selective inhibitor of phosphodiesterase 9; structure in first source | 2.21 | 1 | 0 | ||
| bay 60-7550 [no description available] | 2.21 | 1 | 0 |
| Condition | Indicated | Relationship Strength | Studies | Trials |
|---|---|---|---|---|
| Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. | 0 | 6.29 | 14 | 0 |
| Disease, Pulmonary [description not available] | 0 | 3.92 | 2 | 1 |
| Emesis [description not available] | 0 | 4.01 | 4 | 0 |
| Lung Diseases Pathological processes involving any part of the LUNG. | 0 | 3.92 | 2 | 1 |
| Vomiting The forcible expulsion of the contents of the STOMACH through the MOUTH. | 0 | 4.01 | 4 | 0 |
| Brain Disorders [description not available] | 0 | 2.21 | 1 | 0 |
| Fra(X) Syndrome [description not available] | 0 | 2.21 | 1 | 0 |
| Brain Diseases Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM. | 0 | 2.21 | 1 | 0 |
| Fragile X Syndrome A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226) | 0 | 2.21 | 1 | 0 |
| Polyarthritis [description not available] | 0 | 4.68 | 5 | 0 |
| Allergic Encephalomyelitis [description not available] | 0 | 2.21 | 1 | 0 |
| MS (Multiple Sclerosis) [description not available] | 0 | 2.21 | 1 | 0 |
| Arthritis Acute or chronic inflammation of JOINTS. | 0 | 9.68 | 5 | 0 |
| Multiple Sclerosis An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903) | 0 | 2.21 | 1 | 0 |
| Palmoplantaris Pustulosis [description not available] | 0 | 22.22 | 358 | 74 |
| Psoriasis A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. | 1 | 26.98 | 716 | 148 |
| Acute Onset Vascular Dementia [description not available] | 0 | 2.25 | 1 | 0 |
| Dementia, Vascular An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44) | 0 | 2.25 | 1 | 0 |
| Hospital-Acquired Condition [description not available] | 0 | 3.33 | 1 | 0 |
| Complications of Diabetes Mellitus [description not available] | 0 | 3.33 | 1 | 0 |
| Infection [description not available] | 0 | 8.64 | 2 | 0 |
| Benign Neoplasms [description not available] | 0 | 9.36 | 10 | 4 |
| Granuloma Annulare Benign granulomatous disease of unknown etiology characterized by a ring of localized or disseminated papules or nodules on the skin and palisading histiocytes surrounding necrobiotic tissue resulting from altered collagen structures. | 0 | 9.15 | 2 | 0 |
| Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. | 0 | 3.64 | 2 | 0 |
| Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. | 0 | 9.36 | 10 | 4 |
| Benign Chronic Pemphigus [description not available] | 0 | 9.44 | 6 | 0 |
| Dermatomyositis, Adult Type [description not available] | 0 | 6.19 | 4 | 2 |
| Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6) | 1 | 8.19 | 4 | 2 |
| 2019 Novel Coronavirus Disease [description not available] | 0 | 4.16 | 12 | 0 |
| Innate Inflammatory Response [description not available] | 0 | 10.8 | 18 | 3 |
| Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. | 0 | 10.8 | 18 | 3 |
| Psoriasis Arthropathica [description not available] | 0 | 20.86 | 181 | 59 |
| Arthritis, Psoriatic A type of inflammatory arthritis associated with PSORIASIS, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of HLA-B27-associated SPONDYLARTHROPATHY, and the absence of rheumatoid factor. | 1 | 27.86 | 181 | 59 |
| Mouth Ulcer [description not available] | 0 | 12.62 | 20 | 11 |
| Adamantiades-Behcet Disease [description not available] | 0 | 14.05 | 36 | 12 |
| Behcet Syndrome Rare chronic inflammatory disease involving the small blood vessels. It is of unknown etiology and characterized by mucocutaneous ulceration in the mouth and genital region and uveitis with hypopyon. The neuro-ocular form may cause blindness and death. SYNOVITIS; THROMBOPHLEBITIS; gastrointestinal ulcerations; RETINAL VASCULITIS; and OPTIC ATROPHY may occur as well. | 1 | 21.05 | 36 | 12 |
| Skin Ulcer An ULCER of the skin and underlying tissues. | 0 | 3.33 | 1 | 0 |
| Ulcer A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue. | 0 | 8.33 | 1 | 0 |
| Oral Ulcer A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis (STOMATITIS, APHTHOUS); NOMA; necrotizing gingivitis (GINGIVITIS, NECROTIZING ULCERATIVE); TOOTHBRUSHING; and various irritants. (From Jablonski, Dictionary of Dentistry, 1992, p842) | 1 | 14.62 | 20 | 11 |
| Airflow Obstruction, Chronic [description not available] | 0 | 3.7 | 3 | 0 |
| Pulmonary Disease, Chronic Obstructive A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA. | 0 | 3.7 | 3 | 0 |
| Bullous Dermatoses [description not available] | 0 | 6.55 | 12 | 1 |
| Acute Disease Disease having a short and relatively severe course. | 0 | 4.31 | 3 | 1 |
| Cirrhosis, Liver [description not available] | 0 | 2.41 | 1 | 0 |
| Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. | 0 | 2.41 | 1 | 0 |
| Borderline Lepromatous [description not available] | 0 | 3.23 | 4 | 0 |
| Erythema Nodosum An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. | 0 | 3.4 | 5 | 0 |
| Cold Panniculitis [description not available] | 0 | 2.41 | 1 | 0 |
| Leprosy, Cutaneous [description not available] | 0 | 3.23 | 4 | 0 |
| Insulin Sensitivity [description not available] | 0 | 4.39 | 3 | 1 |
| Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. | 0 | 9.39 | 3 | 1 |
| Cirrhosis [description not available] | 0 | 4.15 | 4 | 0 |
| Dermatosclerosis [description not available] | 0 | 2.41 | 1 | 0 |
| Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. | 0 | 9.15 | 4 | 0 |
| Scleroderma, Localized A term used to describe a variety of localized asymmetrical SKIN thickening that is similar to those of SYSTEMIC SCLERODERMA but without the disease features in the multiple internal organs and BLOOD VESSELS. Lesions may be characterized as patches or plaques (morphea), bands (linear), or nodules. | 0 | 2.41 | 1 | 0 |
| Chronic Illness [description not available] | 0 | 11.75 | 21 | 5 |
| Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). | 0 | 11.75 | 21 | 5 |
| Lichen Planus, Oral Oral lesions accompanying cutaneous lichen planus or often occurring alone. The buccal mucosa, lips, gingivae, floor of the mouth, and palate are usually affected (in a descending order of frequency). Typically, oral lesions consist of radiating white or gray, velvety, threadlike lines, arranged in a reticular pattern, at the intersection of which there may be minute, white, elevated dots or streaks (Wickham's striae). (Jablonski, Illustrated Dictionary of Dentistry) | 1 | 4.61 | 2 | 0 |
| Aphthae [description not available] | 0 | 3.68 | 7 | 0 |
| Stomatitis, Aphthous A recurrent disease of the oral mucosa of unknown etiology. It is characterized by small white ulcerative lesions, single or multiple, round or oval. Two to eight crops of lesions occur per year, lasting for 7 to 14 days and then heal without scarring. (From Jablonski's Dictionary of Dentistry, 1992, p742) | 0 | 3.68 | 7 | 0 |
| Cardiovascular Diseases Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM. | 0 | 8.97 | 11 | 5 |
| Exanthem [description not available] | 0 | 4.62 | 7 | 0 |
| Acrodermatitis Inflammation involving the skin of the extremities, especially the hands and feet. Several forms are known, some idiopathic and some hereditary. The infantile form is called Gianotti-Crosti syndrome. | 0 | 3.36 | 5 | 0 |
| Exanthema Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology. | 0 | 4.62 | 7 | 0 |
| Vitiligo A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. | 1 | 9.66 | 6 | 3 |
| Enthesopathy A disorder occurring at the site of insertion of TENDONS or LIGAMENTS into bones or JOINT CAPSULES. | 0 | 5.2 | 2 | 1 |
| Arthropathies [description not available] | 0 | 4.72 | 1 | 1 |
| Joint Diseases Diseases involving the JOINTS. | 0 | 4.72 | 1 | 1 |
| Cicatrix, Hypertrophic An elevated scar, resembling a KELOID, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. | 0 | 2.31 | 1 | 0 |
| Chronic Insomnia [description not available] | 0 | 2.41 | 1 | 0 |
| Sleep Initiation and Maintenance Disorders Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition. | 0 | 2.41 | 1 | 0 |
| Suicidal Ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm. | 0 | 2.63 | 2 | 0 |
| HIV Coinfection [description not available] | 0 | 4.37 | 6 | 0 |
| HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). | 0 | 4.37 | 6 | 0 |
| Acne [description not available] | 0 | 7.41 | 1 | 0 |
| Acne Vulgaris A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. | 1 | 4.41 | 1 | 0 |
| Atherogenesis [description not available] | 0 | 2.41 | 1 | 0 |
| Atherosclerosis A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA. | 0 | 7.41 | 1 | 0 |
| Recrudescence [description not available] | 0 | 3.13 | 4 | 0 |
| Ache [description not available] | 0 | 7.26 | 5 | 4 |
| Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. | 0 | 12.26 | 5 | 4 |
| Acne Inversa [description not available] | 0 | 7.63 | 10 | 3 |
| Colitis, Granulomatous [description not available] | 0 | 4.13 | 4 | 0 |
| Crohn Disease A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients. | 0 | 4.13 | 4 | 0 |
| Hidradenitis Suppurativa A chronic suppurative and cicatricial disease of the apocrine glands occurring chiefly in the axillae in women and in the groin and anal regions in men. It is characterized by poral occlusion with secondary bacterial infection, evolving into abscesses which eventually rupture. As the disease becomes chronic, ulcers appear, sinus tracts enlarge, fistulas develop, and fibrosis and scarring become evident. | 1 | 9.63 | 10 | 3 |
| Cerebral Infarction, Middle Cerebral Artery [description not available] | 0 | 2.41 | 1 | 0 |
| Apoplexy [description not available] | 0 | 3.01 | 3 | 0 |
| Acute Ischemic Stroke [description not available] | 0 | 2.41 | 1 | 0 |
| Cerebral Ischemia [description not available] | 0 | 2.41 | 1 | 0 |
| Ischemic Stroke Stroke due to BRAIN ISCHEMIA resulting in interruption or reduction of blood flow to a part of the brain. When obstruction is due to a BLOOD CLOT formed within in a cerebral blood vessel it is a thrombotic stroke. When obstruction is formed elsewhere and moved to block a cerebral blood vessel (see CEREBRAL EMBOLISM) it is referred to as embolic stroke. Wake-up stroke refers to ischemic stroke occurring during sleep while cryptogenic stroke refers to ischemic stroke of unknown origin. | 0 | 2.41 | 1 | 0 |
| Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION. | 0 | 2.41 | 1 | 0 |
| Infarction, Middle Cerebral Artery NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction. | 0 | 2.41 | 1 | 0 |
| Stroke A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810) | 0 | 3.01 | 3 | 0 |
| Acute Respiratory Distress Syndrome [description not available] | 0 | 7.6 | 1 | 0 |
| Respiratory Distress Syndrome A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA. | 0 | 7.6 | 1 | 0 |
| Bowel Diseases, Inflammatory [description not available] | 0 | 5.75 | 7 | 0 |
| Inflammatory Bowel Diseases Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS. | 0 | 5.75 | 7 | 0 |
| Binge Alcohol Consumption [description not available] | 0 | 2.41 | 1 | 0 |
| Lupus Erythematosus, Cutaneous, Subacute [description not available] | 0 | 2.41 | 1 | 0 |
| Lupus Erythematosus, Cutaneous A form of lupus erythematosus in which the skin may be the only organ involved or in which skin involvement precedes the spread into other body systems. It has been classified into three forms - acute (= LUPUS ERYTHEMATOSUS, SYSTEMIC with skin lesions), subacute, and chronic (= LUPUS ERYTHEMATOSUS, DISCOID). | 0 | 2.41 | 1 | 0 |
| Chronic Bullous Disease of Childhood [description not available] | 0 | 3.52 | 4 | 0 |
| Bleb [description not available] | 0 | 2.6 | 1 | 0 |
| Pemphigus Foliaceus [description not available] | 0 | 2.76 | 2 | 0 |
| Pemphigus Group of chronic blistering diseases characterized histologically by ACANTHOLYSIS and blister formation within the EPIDERMIS. | 0 | 2.76 | 2 | 0 |
| Alcohol Abuse [description not available] | 0 | 3.99 | 1 | 1 |
| Alcohol Drinking Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking. | 0 | 4.07 | 2 | 1 |
| Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4) | 1 | 5.99 | 1 | 1 |
| Eczema, Atopic [description not available] | 0 | 10.07 | 14 | 4 |
| Dermatitis, Atopic A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema. | 1 | 12.07 | 14 | 4 |
| Mucositis, Oral [description not available] | 0 | 2.6 | 1 | 0 |
| Stomatitis INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP. | 0 | 7.6 | 1 | 0 |
| Acute Confusional Senile Dementia [description not available] | 0 | 2.6 | 1 | 0 |
| Diabetes Mellitus, Adult-Onset [description not available] | 0 | 4.35 | 3 | 1 |
| Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) | 0 | 2.6 | 1 | 0 |
| Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY. | 0 | 4.35 | 3 | 1 |
| Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions. | 0 | 2.6 | 1 | 0 |
| Cancer of Skin [description not available] | 0 | 2.6 | 1 | 0 |
| Feuerstein-Mims Syndrome [description not available] | 0 | 2.6 | 1 | 0 |
| Skin Neoplasms Tumors or cancer of the SKIN. | 0 | 2.6 | 1 | 0 |
| Itching [description not available] | 0 | 9.91 | 12 | 5 |
| Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. | 0 | 9.91 | 12 | 5 |
| Dermatitis Exfoliativa [description not available] | 0 | 2.98 | 3 | 0 |
| Papulosquamous Disorders [description not available] | 0 | 2.6 | 1 | 0 |
| Dermatitis, Exfoliative The widespread involvement of the skin by a scaly, erythematous dermatitis occurring either as a secondary or reactive process to an underlying cutaneous disorder (e.g., atopic dermatitis, psoriasis, etc.), or as a primary or idiopathic disease. It is often associated with the loss of hair and nails, hyperkeratosis of the palms and soles, and pruritus. (From Dorland, 27th ed) | 0 | 2.98 | 3 | 0 |
| Sclerosis, Systemic [description not available] | 0 | 3.57 | 2 | 0 |
| Scleroderma, Systemic A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA. | 0 | 3.57 | 2 | 0 |
| Pityriasis Rubra Pilaris A chronic skin disease characterized by small follicular papules, disseminated reddish-brown scaly patches, and often, palmoplantar hyperkeratosis. The papules are about the size of a pin and topped by a horny plug. | 0 | 3.08 | 4 | 0 |
| Alopecia Circumscripta [description not available] | 0 | 4.96 | 7 | 1 |
| Alopecia Areata Loss of scalp and body hair involving microscopically inflammatory patchy areas. | 0 | 4.96 | 7 | 1 |
| Hansen Disease [description not available] | 0 | 2.25 | 1 | 0 |
| Leprosy A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. | 0 | 2.25 | 1 | 0 |
| Scalp Dermatoses Skin diseases involving the SCALP. | 0 | 6.29 | 6 | 2 |
| Hand Dermatosis [description not available] | 0 | 7.04 | 5 | 2 |
| Foot Dermatoses Skin diseases of the foot, general or unspecified. | 0 | 6.85 | 4 | 2 |
| Hand Dermatoses Skin diseases involving the HANDS. | 0 | 7.04 | 5 | 2 |
| Weight Reduction [description not available] | 0 | 5.6 | 5 | 0 |
| Diarrhea An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight. | 0 | 11.05 | 17 | 9 |
| Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. | 0 | 10.61 | 14 | 8 |
| Weight Loss Decrease in existing BODY WEIGHT. | 0 | 5.6 | 5 | 0 |
| Symptom Cluster [description not available] | 0 | 2.21 | 1 | 0 |
| Bone Inflammation [description not available] | 0 | 2.63 | 2 | 0 |
| Syndrome A characteristic symptom complex. | 0 | 2.21 | 1 | 0 |
| Colitis Gravis [description not available] | 0 | 7.04 | 5 | 1 |
| Colitis, Ulcerative Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN. | 1 | 9.04 | 5 | 1 |
| Ankylosing Spondylarthritis [description not available] | 0 | 9.33 | 8 | 4 |
| Spondylitis, Ankylosing A chronic inflammatory condition affecting the axial joints, such as the SACROILIAC JOINT and other intervertebral or costovertebral joints. It occurs predominantly in young males and is characterized by pain and stiffness of joints (ANKYLOSIS) with inflammation at tendon insertions. | 1 | 11.33 | 8 | 4 |
| Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. | 0 | 7.25 | 1 | 0 |
| Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. | 0 | 14.38 | 9 | 4 |
| Prurigo A name applied to several itchy skin eruptions of unknown cause. The characteristic course is the formation of a dome-shaped papule with a small transient vesicle on top, followed by crusting over or lichenification. (From Dorland, 27th ed) | 0 | 7.25 | 1 | 0 |
| Nail Diseases Diseases of the nail plate and tissues surrounding it. The concept is limited to primates. | 0 | 13.31 | 26 | 2 |
| Cardiovascular Stroke [description not available] | 0 | 2.69 | 2 | 0 |
| Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION). | 0 | 7.69 | 2 | 0 |
| Pyoderma Gangrenosum An idiopathic, rapidly evolving, and severely debilitating disease occurring most commonly in association with chronic ulcerative colitis. It is characterized by the presence of boggy, purplish ulcers with undermined borders, appearing mostly on the legs. The majority of cases are in people between 40 and 60 years old. Its etiology is unknown. | 0 | 7.25 | 1 | 0 |
| Infections, Coronavirus [description not available] | 0 | 3.17 | 4 | 0 |
| Pneumonia, Viral Inflammation of the lung parenchyma that is caused by a viral infection. | 0 | 3.17 | 4 | 0 |
| Coronavirus Infections Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE). | 0 | 3.17 | 4 | 0 |
| Opportunistic Infections An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. | 0 | 2.25 | 1 | 0 |
| Anaplastic Oligodendroglioma [description not available] | 0 | 2.25 | 1 | 0 |
| Oligodendroglioma A relatively slow-growing glioma that is derived from oligodendrocytes and tends to occur in the cerebral hemispheres, thalamus, or lateral ventricle. They may present at any age, but are most frequent in the third to fifth decades, with an earlier incidence peak in the first decade. Histologically, these tumors are encapsulated, relatively avascular, and tend to form cysts and microcalcifications. Neoplastic cells tend to have small round nuclei surrounded by unstained nuclei. The tumors may vary from well-differentiated to highly anaplastic forms. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2052; Adams et al., Principles of Neurology, 6th ed, p655) | 0 | 2.25 | 1 | 0 |
| Rheumatoid Arthritis [description not available] | 0 | 5.11 | 3 | 1 |
| Arthritis, Rheumatoid A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. | 1 | 7.11 | 3 | 1 |
| Facial Dermatoses Skin diseases involving the FACE. | 0 | 2.88 | 3 | 0 |
| Granulomas [description not available] | 0 | 2.25 | 1 | 0 |
| Granuloma A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. | 0 | 2.25 | 1 | 0 |
| Licheniform Eruptions [description not available] | 0 | 2.25 | 1 | 0 |
| Actinic Reticuloid Syndrome [description not available] | 0 | 2.69 | 2 | 0 |
| Bladder Cancer [description not available] | 0 | 2.25 | 1 | 0 |
| Urinary Bladder Neoplasms Tumors or cancer of the URINARY BLADDER. | 0 | 2.25 | 1 | 0 |
| Cytokine Release Syndrome A severe immune reaction characterized by excessive release of CYTOKINES. Symptoms include DYSPNEA; FEVER; HEADACHE; HYPOTENSION; NAUSEA; RASH; TACHYCARDIA; HYPOXIA; HYPERFERRITINEMIA, and MULTIPLE ORGAN FAILURE. It is associated with viral infections, SEPSIS; AUTOIMMUNE DISEASES and a variety of factors used in IMMUNOTHERAPY. | 0 | 2.69 | 2 | 0 |
| Bilateral Headache [description not available] | 0 | 10.61 | 14 | 8 |
| Headache The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS. | 0 | 10.61 | 14 | 8 |
| Granulomatosis, Orofacial A condition characterized by persistent or recurrent labial enlargement, ORAL ULCER, and other orofacial manifestations in the absence of identifiable CROHN DISEASE; or SARCOIDOSIS. Among experts there is disagreement on whether orofacial granulomatosis is a distinct clinical disorder or an initial presentation of Crohn disease. | 0 | 2.25 | 1 | 0 |
| Rheumatism [description not available] | 0 | 3.51 | 2 | 0 |
| Rheumatic Diseases Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. | 0 | 3.51 | 2 | 0 |
| Arthritis, Spinal [description not available] | 0 | 4.29 | 3 | 0 |
| Autoimmune Disease [description not available] | 0 | 4.22 | 3 | 0 |
| Autoimmune Diseases Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides. | 0 | 4.22 | 3 | 0 |
| Uveitis Inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (sclera and cornea, and the retina). (Dorland, 27th ed) | 1 | 9.25 | 1 | 0 |
| Malignant Melanoma [description not available] | 0 | 2.31 | 1 | 0 |
| Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) | 0 | 7.31 | 1 | 0 |
| Dermatoses [description not available] | 0 | 6.73 | 4 | 1 |
| Skin Diseases Diseases involving the DERMIS or EPIDERMIS. | 0 | 6.73 | 4 | 1 |
| Koch's Disease [description not available] | 0 | 2.31 | 1 | 0 |
| Tuberculosis Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS. | 0 | 2.31 | 1 | 0 |
| Colorectal Cancer [description not available] | 0 | 2.61 | 2 | 0 |
| Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. | 0 | 2.61 | 2 | 0 |
| Hyperkeratosis Palmaris et Plantaris [description not available] | 0 | 2.31 | 1 | 0 |
| Acute Symptom Flare [description not available] | 0 | 3.8 | 3 | 0 |
| Intestinal Diseases Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM. | 0 | 3.55 | 2 | 0 |
| Lichen Ruber Planus [description not available] | 0 | 5.42 | 2 | 2 |
| Lichen Planus An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flat-topped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a saw-tooth pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. | 1 | 7.42 | 2 | 2 |
| Dermatitis, Eczematous [description not available] | 0 | 3.82 | 3 | 0 |
| Eczema A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). | 1 | 5.82 | 3 | 0 |
| Mouth Diseases Diseases involving the MOUTH. | 0 | 2.15 | 1 | 0 |
| Erythema Multiforme A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic bull's-eye lesions usually occurring on the dorsal aspect of the hands and forearms. | 0 | 8.48 | 2 | 0 |
| Sore Throat [description not available] | 0 | 2.15 | 1 | 0 |
| Group A Strep Infection [description not available] | 0 | 2.15 | 1 | 0 |
| Pharyngitis Inflammation of the throat (PHARYNX). | 0 | 2.15 | 1 | 0 |
| Streptococcal Infections Infections with bacteria of the genus STREPTOCOCCUS. | 0 | 2.15 | 1 | 0 |
| Tonsillitis Inflammation of the tonsils, especially the PALATINE TONSILS but the ADENOIDS (pharyngeal tonsils) and lingual tonsils may also be involved. Tonsillitis usually is caused by bacterial infection. Tonsillitis may be acute, chronic, or recurrent. | 0 | 2.15 | 1 | 0 |
| Nasopharyngitis Inflammation of the NASOPHARYNX, usually including its mucosa, related lymphoid structure, and glands. | 0 | 8.65 | 6 | 6 |
| Headache, Tension [description not available] | 0 | 8.16 | 5 | 5 |
| Infections, Respiratory [description not available] | 0 | 8.16 | 5 | 5 |
| Respiratory Tract Infections Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases. | 0 | 8.16 | 5 | 5 |
| Tension-Type Headache A common primary headache disorder, characterized by a dull, non-pulsatile, diffuse, band-like (or vice-like) PAIN of mild to moderate intensity in the HEAD; SCALP; or NECK. The subtypes are classified by frequency and severity of symptoms. There is no clear cause even though it has been associated with MUSCLE CONTRACTION and stress. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1) | 0 | 8.16 | 5 | 5 |
| Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted [description not available] | 0 | 2.15 | 1 | 0 |
| Hepatitis C INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown. | 0 | 7.15 | 1 | 0 |
| Eye Disorders [description not available] | 0 | 3.06 | 1 | 0 |
| Eye Diseases Diseases affecting the eye. | 0 | 3.06 | 1 | 0 |
| Petechiae Pinhead size (3 mm) skin discolorization due to hemorrhage. | 0 | 2.15 | 1 | 0 |
| Spider Veins [description not available] | 0 | 2.15 | 1 | 0 |
| Purpura Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. When the size of the discolorization is | 0 | 7.15 | 1 | 0 |
| Telangiectasis Permanent dilation of preexisting blood vessels (CAPILLARIES; ARTERIOLES; VENULES) creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. | 0 | 2.15 | 1 | 0 |
| Metabolic Acidosis [description not available] | 0 | 2.15 | 1 | 0 |
| Acidosis, Renal Tubular, Type I [description not available] | 0 | 2.15 | 1 | 0 |
| Adult Fanconi Syndrome [description not available] | 0 | 2.15 | 1 | 0 |
| Hypokalemia Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed) | 0 | 2.15 | 1 | 0 |
| Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up. | 0 | 7.15 | 1 | 0 |
| Acidosis, Renal Tubular A group of genetic disorders of the KIDNEY TUBULES characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic ACIDOSIS. Defective renal acidification of URINE (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as HYPOKALEMIA, hypercalcinuria with NEPHROLITHIASIS and NEPHROCALCINOSIS, and RICKETS. | 0 | 2.15 | 1 | 0 |
| Proteinuria The presence of proteins in the urine, an indicator of KIDNEY DISEASES. | 0 | 2.15 | 1 | 0 |
| Disease Exacerbation [description not available] | 0 | 4.42 | 4 | 0 |
| Pyogenic Sacroiliitis [description not available] | 0 | 3.44 | 2 | 0 |
| Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. | 0 | 2.17 | 1 | 0 |
| Joint Pain [description not available] | 0 | 3.99 | 4 | 0 |
| Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY). | 0 | 3.97 | 2 | 1 |
| Arthralgia Pain in the joint. | 0 | 3.99 | 4 | 0 |
| Bechterew Syndrome [description not available] | 0 | 4.99 | 4 | 0 |
| Spondylarthropathies Heterogeneous group of arthritic diseases sharing clinical and radiologic features. They are associated with the HLA-B27 ANTIGEN and some with a triggering infection. Most involve the axial joints in the SPINE, particularly the SACROILIAC JOINT, but can also involve asymmetric peripheral joints. Subsets include ANKYLOSING SPONDYLITIS; REACTIVE ARTHRITIS; PSORIATIC ARTHRITIS; and others. | 0 | 4.99 | 4 | 0 |
| Adverse Drug Event [description not available] | 0 | 3.79 | 3 | 0 |
| Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals. | 0 | 3.79 | 3 | 0 |
| SAPHO Syndrome [description not available] | 0 | 7.58 | 2 | 0 |
| Acquired Hyperostosis Syndrome Syndrome consisting of SYNOVITIS; ACNE CONGLOBATA; PALMOPLANTAR PUSTULOSIS; HYPEROSTOSIS; and OSTEITIS. The most common site of the disease is the upper anterior chest wall, characterized by predominantly osteosclerotic lesions, hyperostosis, and arthritis of the adjacent joints. The association of sterile inflammatory bone lesions and neutrophilic skin eruptions is indicative of this syndrome. | 0 | 2.58 | 2 | 0 |
| Lassitude [description not available] | 0 | 6.05 | 3 | 1 |
| Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. | 0 | 6.05 | 3 | 1 |
| Hypermelanosis [description not available] | 0 | 2.59 | 2 | 0 |
| Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. | 0 | 7.59 | 2 | 0 |
| Herpes Simplex Virus Infection [description not available] | 0 | 3.09 | 1 | 0 |
| Mycoplasma dispar Infection [description not available] | 0 | 3.09 | 1 | 0 |
| Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.) | 0 | 3.09 | 1 | 0 |
| Hyperplasia, Reactive Lymphoid [description not available] | 0 | 3.09 | 1 | 0 |
| Mange, Sarcoptic [description not available] | 0 | 3.09 | 1 | 0 |
| Great Pox [description not available] | 0 | 3.09 | 1 | 0 |
| Skin Syphilis [description not available] | 0 | 3.09 | 1 | 0 |
| Scabies A contagious cutaneous inflammation caused by the bite of the mite SARCOPTES SCABIEI. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. | 0 | 3.09 | 1 | 0 |
| Syphilis A contagious venereal disease caused by the spirochete TREPONEMA PALLIDUM. | 0 | 3.09 | 1 | 0 |
| Alcoholic Intoxication An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES. | 0 | 2.17 | 1 | 0 |
| Acute Liver Injury, Drug-Induced [description not available] | 0 | 2.59 | 2 | 0 |
| Long Sleeper Syndrome [description not available] | 0 | 2.17 | 1 | 0 |
| Sleep Wake Disorders Abnormal sleep-wake schedule or pattern associated with the CIRCADIAN RHYTHM which affect the length, timing, and/or rigidity of the sleep-wake cycle relative to the day-night cycle. | 0 | 2.17 | 1 | 0 |
| Chemical and Drug Induced Liver Injury A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment. | 0 | 2.59 | 2 | 0 |
| Pemphigoid [description not available] | 0 | 7.17 | 1 | 0 |
| Pemphigoid, Bullous A chronic and relatively benign subepidermal blistering disease usually of the elderly and without histopathologic acantholysis. | 0 | 2.17 | 1 | 0 |
| Lentigines [description not available] | 0 | 2.87 | 3 | 0 |
| Lentigo Small circumscribed melanoses resembling, but differing histologically from, freckles. The concept includes senile lentigo ('liver spots') and nevoid lentigo (nevus spilus, lentigo simplex) and may also occur in association with multiple congenital defects or congenital syndromes (e.g., Peutz-Jeghers syndrome). | 0 | 2.87 | 3 | 0 |
| EBS-DM [description not available] | 0 | 4 | 2 | 1 |
| Epidermolysis Bullosa Simplex A form of epidermolysis bullosa characterized by serous bullae that heal without scarring. Mutations in the genes that encode KERATIN-5 and KERATIN-14 have been associated with several subtypes of epidermolysis bullosa simplex. | 0 | 9 | 2 | 1 |
| Pink Eye [description not available] | 0 | 2.17 | 1 | 0 |
| Epiphora [description not available] | 0 | 2.17 | 1 | 0 |
| Conjunctivitis INFLAMMATION of the CONJUNCTIVA. | 0 | 2.17 | 1 | 0 |
| Lacrimal Apparatus Diseases Diseases of the LACRIMAL APPARATUS. | 0 | 2.17 | 1 | 0 |
| Cardiac Toxicity [description not available] | 0 | 2.55 | 2 | 0 |
| Cardiotoxicity Damage to the HEART or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION. | 0 | 7.55 | 2 | 0 |
| Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. | 0 | 8.13 | 10 | 9 |
| Adult Periodontitis [description not available] | 0 | 3.56 | 1 | 1 |
| Familial Nonmedullary Thyroid Cancer [description not available] | 0 | 3.56 | 1 | 1 |
| Affective Psychosis, Bipolar [description not available] | 0 | 3.56 | 1 | 1 |
| Arteriosclerosis, Coronary [description not available] | 0 | 3.56 | 1 | 1 |
| Health Care Associated Infection [description not available] | 0 | 3.56 | 1 | 1 |
| Intertrochanteric Fractures [description not available] | 0 | 3.56 | 1 | 1 |
| Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. | 0 | 3.56 | 1 | 1 |
| Blood Pressure, High [description not available] | 0 | 5.66 | 4 | 4 |
| Cells, Neoplasm Circulating [description not available] | 0 | 3.56 | 1 | 1 |
| Polycystic Ovarian Syndrome [description not available] | 0 | 3.56 | 1 | 1 |
| Cancer of the Thyroid [description not available] | 0 | 3.56 | 1 | 1 |
| Alveolar Bone Atrophy [description not available] | 0 | 3.56 | 1 | 1 |
| Diabetes Mellitus, Gestational [description not available] | 0 | 3.56 | 1 | 1 |
| Bacterial Infections, Gram-Negative [description not available] | 0 | 3.56 | 1 | 1 |
| Local Neoplasm Recurrence [description not available] | 0 | 3.56 | 1 | 1 |
| Anovulation Suspension or cessation of OVULATION in animals or humans with follicle-containing ovaries (OVARIAN FOLLICLE). Depending on the etiology, OVULATION may be induced with appropriate therapy. | 0 | 3.56 | 1 | 1 |
| Bipolar Disorder A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. | 0 | 3.56 | 1 | 1 |
| Coronary Artery Disease Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause. | 0 | 3.56 | 1 | 1 |
| Cross Infection Any infection which a patient contracts in a health-care institution. | 0 | 3.56 | 1 | 1 |
| Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE. | 0 | 3.56 | 1 | 1 |
| Electrolytes Substances that dissociate into two or more ions, to some extent, in water. Solutions of electrolytes thus conduct an electric current and can be decomposed by it (ELECTROLYSIS). (Grant & Hackh's Chemical Dictionary, 5th ed) | 0 | 3.56 | 1 | 1 |
| Hip Fractures Fractures of the FEMUR HEAD; the FEMUR NECK; (FEMORAL NECK FRACTURES); the trochanters; or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region (FEMORAL FRACTURES). | 0 | 3.56 | 1 | 1 |
| Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. | 0 | 5.66 | 4 | 4 |
| Polycystic Ovary Syndrome A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading. | 0 | 3.56 | 1 | 1 |
| Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) | 0 | 3.56 | 1 | 1 |
| Thyroid Neoplasms Tumors or cancer of the THYROID GLAND. | 0 | 3.56 | 1 | 1 |
| Urinary Tract Infections Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA. | 0 | 3.56 | 1 | 1 |
| Diabetes, Gestational Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA. | 0 | 3.56 | 1 | 1 |
| Gram-Negative Bacterial Infections Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method. | 0 | 3.56 | 1 | 1 |
| Lung Injury, Acute [description not available] | 0 | 2.21 | 1 | 0 |
| Vascular Injuries [description not available] | 0 | 7.21 | 1 | 0 |
| Kahler Disease [description not available] | 0 | 2.21 | 1 | 0 |
| Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. | 0 | 2.21 | 1 | 0 |
| Acute Lung Injury A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological). | 0 | 2.21 | 1 | 0 |
| Libman-Sacks Disease [description not available] | 0 | 2.48 | 2 | 0 |
| Lupus Erythematosus, Systemic A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. | 0 | 2.48 | 2 | 0 |
| Dermatitis Medicamentosa [description not available] | 0 | 2.21 | 1 | 0 |
| Graft-Versus-Host Disease [description not available] | 0 | 8.5 | 2 | 0 |
| Acute Myelogenous Leukemia [description not available] | 0 | 2.21 | 1 | 0 |
| Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. | 0 | 3.5 | 2 | 0 |
| Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES. | 0 | 2.21 | 1 | 0 |
| Connective Tissue Disease, Mixed [description not available] | 0 | 2.25 | 1 | 0 |
| Chronic Kidney Diseases [description not available] | 0 | 2.21 | 1 | 0 |
| Auricular Fibrillation [description not available] | 0 | 2.21 | 1 | 0 |
| Cardiac Failure [description not available] | 0 | 2.21 | 1 | 0 |
| Atrial Fibrillation Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation. | 0 | 7.21 | 1 | 0 |
| Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. | 0 | 7.21 | 1 | 0 |
| Renal Insufficiency, Chronic Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002) | 0 | 2.21 | 1 | 0 |
| Hepatitis B Virus Infection [description not available] | 0 | 2.21 | 1 | 0 |
| Hepatitis B INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact. | 0 | 2.21 | 1 | 0 |
| Diffuse Lymphocytic Lymphoma, Poorly-Differentiated [description not available] | 0 | 2.21 | 1 | 0 |
| Lymphoma, Mantle-Cell A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1). | 0 | 2.21 | 1 | 0 |
| Carcinoma, Non-Small Cell Lung [description not available] | 0 | 2.21 | 1 | 0 |
| Cancer of Lung [description not available] | 0 | 2.21 | 1 | 0 |
| Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. | 0 | 2.21 | 1 | 0 |
| Lung Neoplasms Tumors or cancer of the LUNG. | 0 | 2.21 | 1 | 0 |
| Cholera Infantum [description not available] | 0 | 5.62 | 3 | 1 |
| Alopecia Cicatrisata [description not available] | 0 | 3.17 | 1 | 0 |
| Cicatrization The formation of fibrous tissue in the place of normal tissue during the process of WOUND HEALING. It includes scar tissue formation occurring in healing internal organs as well as in the skin after surface injuries. | 0 | 3.17 | 1 | 0 |
| Alopecia Absence of hair from areas where it is normally present. | 0 | 3.17 | 1 | 0 |
| Cicatrix The fibrous tissue that replaces normal tissue during the process of WOUND HEALING. | 0 | 3.17 | 1 | 0 |
| Anti-MuSK Myasthenia Gravis [description not available] | 0 | 2.21 | 1 | 0 |
| Myasthenia Gravis A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition. | 0 | 2.21 | 1 | 0 |
| Verruca [description not available] | 0 | 2.21 | 1 | 0 |
| Warts Benign epidermal proliferations or tumors; some are viral in origin. | 0 | 2.21 | 1 | 0 |
| Osteolysis Dissolution of bone that particularly involves the removal or loss of calcium. | 0 | 2.21 | 1 | 0 |
| Granulocytic Leukemia, Chronic [description not available] | 0 | 2.25 | 1 | 0 |
| Leukemia, Myelogenous, Chronic, BCR-ABL Positive Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS. | 0 | 2.25 | 1 | 0 |
| ADDH [description not available] | 0 | 2.1 | 1 | 0 |
| Allergy, Food [description not available] | 0 | 2.1 | 1 | 0 |
| Attention Deficit Disorder with Hyperactivity A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V) | 0 | 2.1 | 1 | 0 |
| Food Hypersensitivity Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens in food. | 0 | 2.1 | 1 | 0 |
| Asthma, Bronchial [description not available] | 0 | 3.38 | 2 | 0 |
| Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL). | 0 | 3.38 | 2 | 0 |
| Dermatitis Any inflammation of the skin. | 1 | 5.01 | 1 | 0 |
| Acne Rosacea [description not available] | 0 | 2.1 | 1 | 0 |
| Rosacea A cutaneous disorder primarily of convexities of the central part of the FACE, such as FOREHEAD; CHEEK; NOSE; and CHIN. It is characterized by FLUSHING; ERYTHEMA; EDEMA; RHINOPHYMA; papules; and ocular symptoms. It may occur at any age but typically after age 30. There are various subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous, and ocular (National Rosacea Society's Expert Committee on the Classification and Staging of Rosacea, J Am Acad Dermatol 2002; 46:584-7). | 1 | 9.1 | 1 | 0 |
| Cardiometabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components not only include metabolic dysfunctions of METABOLIC SYNDROME but also HYPERTENSION, and ABDOMINAL OBESITY. | 0 | 3.01 | 1 | 0 |
| Gout Metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of URIC ACID calculi. | 1 | 5.01 | 1 | 0 |
| Metabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. | 0 | 3.01 | 1 | 0 |
| Female Genital Diseases [description not available] | 0 | 9.73 | 9 | 9 |
| Genital Diseases, Male Pathological processes involving the male reproductive tract (GENITALIA, MALE). | 0 | 9.73 | 9 | 9 |
| Genital Diseases, Female Pathological processes involving the female reproductive tract (GENITALIA, FEMALE). | 0 | 9.73 | 9 | 9 |
| Tendinitis Inflammation of TENDONS. It is characterized by the degeneration of tendons accompanied by an inflammatory repair response, fibroblastic proliferation, and formation of granulation tissue. Tendinitis is not a clinical diagnosis and can be confirmed only by histopathological findings. | 0 | 3.04 | 1 | 0 |
| Tendinopathy Clinical syndrome describing overuse tendon injuries characterized by a combination of PAIN, diffuse or localized swelling, and impaired performance. | 0 | 3.04 | 1 | 0 |
| Kidney Failure A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. | 0 | 2.13 | 1 | 0 |
| Renal Insufficiency Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE. | 0 | 2.13 | 1 | 0 |
| Adjuvant Arthritis [description not available] | 0 | 2.05 | 1 | 0 |
| Besnier-Boeck Disease [description not available] | 0 | 4.37 | 1 | 1 |
| Sarcoidosis An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. | 0 | 9.37 | 1 | 1 |
| Allergic Contact Dermatitis [description not available] | 0 | 3.46 | 1 | 1 |
| Dermatitis, Allergic Contact A contact dermatitis due to allergic sensitization to various substances. These substances subsequently produce inflammatory reactions in the skin of those who have acquired hypersensitivity to them as a result of prior exposure. | 1 | 5.46 | 1 | 1 |
| Lupus Erythematosus, Chronic Cutaneous [description not available] | 0 | 3.46 | 1 | 1 |
| Lupus Erythematosus, Discoid A chronic form of cutaneous lupus erythematosus (LUPUS ERYTHEMATOSUS, CUTANEOUS) in which the skin lesions mimic those of the systemic form but in which systemic signs are rare. It is characterized by the presence of discoid skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy. Lesions are surrounded by an elevated erythematous border. The condition typically involves the face and scalp, but widespread dissemination may occur. | 1 | 5.46 | 1 | 1 |
| Dysmyelopoietic Syndromes [description not available] | 0 | 2.94 | 1 | 0 |
| Myelodysplastic Syndromes Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA. | 0 | 2.94 | 1 | 0 |