| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01039688 | Comparing The Effectiveness And Safety Of 2 Doses Of An Experimental Drug, CP-690,550, To Methotrexate (MTX) In Patients With Rheumatoid Arthritis Who Have Not Previously Received MTX | PHASE3 | COMPLETED | 956 | — | — | Jan 1, 2010 | Mar 1, 2013 | Apr 6, 2018 | 176 | United States, Argentina +28 |
| NCT00960440 | Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors | PHASE3 | COMPLETED | 399 | — | — | Oct 1, 2009 | Mar 1, 2011 | Dec 19, 2018 | 92 | United States, Australia +12 |
| NCT00856544 | A Study Comparing 2 Doses Of CP-690,550 Vs. Placebo For The Treatment Of Rheumatoid Arthritis In Patients On Other Background Arthritis Medications | PHASE3 | COMPLETED | 795 | — | — | May 1, 2009 | Jan 1, 2011 | Jan 10, 2013 | 133 | United States, Australia +18 |
| NCT00847613 | A 2-Year Phase 3 Study Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate | PHASE3 | COMPLETED | 800 | — | — | Mar 1, 2009 | Feb 1, 2012 | May 16, 2024 | 115 | United States, Australia +13 |
| NCT00814307 | A Phase 3 Study Comparing 2 Doses of CP-690,550 vs. Placebo for Treatment of Rheumatoid Arthritis | PHASE3 | COMPLETED | 611 | — | — | Feb 1, 2009 | Jun 1, 2010 | Jan 18, 2013 | 95 | United States, Brazil +14 |
| NCT00413699 | Long-Term Effectiveness And Safety Of CP-690,550 For The Treatment Of Rheumatoid Arthritis | PHASE3 | COMPLETED | 4,488 | — | — | Feb 5, 2007 | Oct 26, 2017 | Oct 30, 2018 | 469 | United States, Argentina +41 |
| NCT00687193 | Comparison Of 5 CP-690,550 Doses Vs. Placebo, For The Treatment Of Rheumatoid Arthritis In Japan | PHASE2 | COMPLETED | 318 | — | — | Mar 1, 2009 | Jul 1, 2010 | Mar 25, 2013 | 40 | Japan |
| NCT00603512 | Comparison Of 4 CP-690,550 Doses Vs. Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis in Japan | PHASE2 | COMPLETED | 140 | — | — | Jan 1, 2008 | Sep 1, 2008 | Jan 25, 2013 | 18 | Japan |
| NCT00413660 | Comparison Of 6 CP-690,550 Doses Vs.Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis | PHASE2 | COMPLETED | 509 | — | — | Jan 1, 2007 | Aug 1, 2008 | Jan 18, 2013 | 82 | United States, Argentina +11 |
| NCT01023100 | A Study Of The Taste Of Different Oral Liquid Preparations Of CP-690,550 In Trained Adult Product Testers | PHASE1 | COMPLETED | 5 | — | — | Mar 1, 2010 | Mar 1, 2010 | Jun 16, 2010 | 1 | United States |
mTSS: sum of erosion and joint space narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score).
mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.
ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender joints count (TJC) or swollen joints count (SJC) and ≥70% improvement in at least 3 of 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability (disability index of the Health Assessment Questionnaire \[HAQ\]), and 5) C-reactive protein (CRP).
BP: pressure exerted by the blood upon the walls of the blood vessels and especially arteries, usually measured on the radial artery using a sphygmomanometer. Systolic BP: the highest arterial blood pressure of a cardiac cycle occurring immediately after systole of the left ventricle of the heart. Diastolic BP: the lowest arterial blood pressure of a cardiac cycle occurring during diastole of the heart.
BP: pressure exerted by the blood upon the walls of the blood vessels and especially arteries, usually measured on the radial artery using a sphygmomanometer. Systolic BP: the highest arterial blood pressure of a cardiac cycle occurring immediately after systole of the left ventricle of the heart. Diastolic BP: the lowest arterial blood pressure of a cardiac cycle occurring during diastole of the heart.
ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joints count (TJC); \>= 20% improvement in swollen joints count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities:dress/groom;arise;eat; walk;reach;grip; hygiene;common activities over past week. Each item scored on 4-point scale from 0-3:0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3:0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR)(millimeter/hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (\<=)3.2 implied low disease activity, greater than (\>)3.2 to 5.1 implied moderate to high disease activity, less than (\<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.
DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeters/hour\[mm/hour\]) and patient's global assessment (PtGA) of disease activity(participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (\<=)3.2 implied low disease activity, greater than (\>)3.2 to 5.1 implied moderate to high disease activity, less than (\<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.
mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.
DAS28-4 (ESR) calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (=\<) 3.2 implied low disease activity, greater than (\>) 3.2 to 5.1 implied moderate to high disease activity and less than (\<) 2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.
DAS28-4 (ESR) calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (=\<) 3.2 implied low disease activity, greater than (\>) 3.2 to 5.1 implied moderate to high disease activity and less than (\<) 2.6=remission.
Treatment-emergent non serious AEs by System Organ Class (SOC) (all causalities) and Laboratory Test Abnormalities (without regard to baseline) The stated number of participants analyzed was the total number of participants in each group (AEs). The actual number of participants analyzed for each laboratory parameter varied, and is provided for each. Abs=absolute; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ESR=erythrocyte sedimentation rate; GGT=gamma glutamyl transferase; hgb=hemoglobin; HDL=high density lipids; LDL=low density lipids; LLN=lower limit of normal; qual=qualitative; Tot=total; ULN=upper limit of normal; WBC=white blood cell
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events.
Criteria for laboratory abnormalities: hemoglobin (Hg), hematocrit, red blood cell (RBC), high density lipoprotein (HDL) cholesterol:\<0.8\*lower limit of normal (LLN), platelet\<0.5\*LLN/\>1.75\*upper limit of normal (ULN), white blood cell (WBC)\<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil, protein, albumin \<0.8\*LLN/\>1.2\*ULN, basophil, eosinophil, monocyte, low density lipoprotein (LDL) cholesterol: \>1.2\*ULN; bilirubin\>1.5\*ULN, aspartate amino transferase(AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\>3.0\*ULN; blood urea nitrogen, creatinine, cholesterol, triglyceride:\>1.3\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN/\>1.1\*ULN; glucose\<0.6\*LLN/\>1.5\*ULN; Urine (specific gravity\<1.003/\>1.030, pH\<4.5/\>8, glucose, ketone, protein, blood/Hg(\>=1; RBC, WBC\>=20; creatinine kinase\>2\*ULN).
Treatment-emergent AEs by SOC (all causalities) - all participants, by time. Data presented for Post Month 96 includes data up to and including Month 114.
Long term safety and tolerability of Tofacitinib was measured as following: percentage (%) of participants with AEs, percentage of participants who discontinued due to AEs. An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.
ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in painful and tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).
| Arm | Type | Description |
|---|---|---|
| 5 mg BID CP-690,550 | EXPERIMENTAL | - |
| 10 mg BID CP-690,550 | EXPERIMENTAL | - |
| methotrexate | ACTIVE_COMPARATOR | - |
| Sequence 1 | EXPERIMENTAL | - |
| Sequence 2 | EXPERIMENTAL | - |
| Sequence 3 | PLACEBO_COMPARATOR | - |
| Sequence 4 | PLACEBO_COMPARATOR | - |
| Active 5 mg | EXPERIMENTAL | - |
| Active 10 mg | EXPERIMENTAL | - |
| Placebo Sequence 1 | PLACEBO_COMPARATOR | Placebo non-responders advance to 5 mg CP-690,550 at Month 3 visit. All patients in this treatment arm advance to 5 mg CP-690,550 at Month 6 visit. |
| Placebo Sequence 2 | PLACEBO_COMPARATOR | Placebo non-responders advance to 10 mg CP-690,550 at Month 3 visit. All patients in this treatment arm advance to 10 mg CP-690,550 at Month 6 visit. |
| Active 5mg | EXPERIMENTAL | - |
| Open-Label Active Treatment Enrolled from Phase 2 | EXPERIMENTAL | Patients enrolling from Phase 2 studies |
| Open-Label Active Treatment Enrolled from Phase 3 | EXPERIMENTAL | Patients enrolling from Phase 3 studies |
| Placebo | PLACEBO_COMPARATOR | - |
| CP-690,550, 10mg | EXPERIMENTAL | - |
| CP-690,550, 15mg | EXPERIMENTAL | - |
| CP-690,550, 1mg | EXPERIMENTAL | - |
| CP-690,550, 3mg | EXPERIMENTAL | - |
| CP-690,550, 5mg | EXPERIMENTAL | - |
| CP-690,550, 0mg | PLACEBO_COMPARATOR | - |
| CP 690,550 1 mg BID | EXPERIMENTAL | - |
| CP 690,550 10 mg BID | EXPERIMENTAL | - |
| CP 690,550 15 mg | EXPERIMENTAL | - |
| CP 690,550 3 mg BID | EXPERIMENTAL | - |
| CP 690,550 5 mg BID | EXPERIMENTAL | - |
| CP-690,550 20 mg QD | EXPERIMENTAL | - |
| Open label | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| CP-690,550 | DRUG | Oral tablets administered at a dose of 5 mg BID for 24 months |
| Disease-modifying antirheumatic drug | DRUG | Oral capsules,administered as 10 mg per week for 4 weeks titrated to 15 mg per week for 4 weeks, then titrated to 20 mg week for 24 months |
| Placebo | DRUG | Oral placebo tablets administered BID daily during the first 3 months of the double-blind, study period. |
| CP 690,550 oral solutions | DRUG | flavored and unflavored prototype CP-690,550 formulations |
Inclusion Criteria: * Adults with moderate to severe RA (Rheumatoid Arthritis) who have not been treated with methotrexate. * Diagnosis of RA based on the American College of Rheumatology 1987 revised criteria. * Active disease as defined by both \>=6 tender or painful joints on motion and \>= 6 jo...