Study Of The Effects Of Atorvastatin On Cholesterol Levels In Rheumatoid Arthritis Patients Taking CP-690,550

Study Overview
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Brief Summary
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All patients will be in instructed to eat a therapeutic lifestyle diet and will receive CP-690,550 throughout the 12 weeks of this study. After 6 weeks, half will receive the cholesterol lowering agent, atorvastatin, and half a matching placebo. This study will first measure the effects of CP-690,550 on cholesterol levels and then the effects of adding atorvastatin on those levels.

Official Title
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Phase 2 Study Of The Effects Of Open-Label CP-690,550 And Double-Blind Atorvastatin On Lipids In Patients With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: CP-690,550
* Drug: Atorvastatin
* Drug: CP-690,550
* Drug: Atorvastatin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: must be diagnosed as having active rheumatoid arthritis agree to participate in the study and sign and informed consent document Exclusion Criteria: History of serious infection within the past 6 months test positive for TB have any uncontrolled clinically significant disease or laboratory tests require administration of prohibited medications during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: CP-690,550<br>* 12 week open-label CP-690,550 10 mg oral tablets administered twice daily starting at Day 0 through Week 12<br>Drug: Atorvastatin<br>* Starting at Week 6 and continuing through Week 12 atorvastatin 10 mg oral tablets administered once daily<br>|
| Experimental: Arm 2<br> | Drug: CP-690,550<br>* 12 week open-label CP-690,550 10 mg oral tablets administered twice daily starting at Day 0 through Week 12<br>Drug: Atorvastatin Placebo<br>* Starting at Week 6 and continuing through Week 12 atorvastatin placebo tablets administered once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline (Week 6) in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Week 12 |  | Baseline (Week 6), Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12 |  | Baseline (Week 6), Week 12 | 
| 12-Hours Fasting Lipid Profile | Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: LDL-C, high-density lipoprotein-cholesterol (HDL-C), very low density lipoprotein-cholesterol (VLDL-C), total cholesterol, apolipoprotein A-1, apolipoprotein B, triglycerides (TGs) and Non-HDL-C. | Day 0, Week 2, 6 (Baseline), 10, 12 | 
| 12-Hours Fasting Lipid Profile: Particle Size of Lipoproteins | Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: plasma lipoprotein VLDL-C, LDL-C and HDL-C particles size. | Day 0, Week 2, 6 (Baseline), 10, 12 | 
| 12-Hours Fasting Lipid Profile: Level of Lipoprotein Particles | Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: total and large VLDL-C and chylomicron particles (VLDLCP), medium and small VLDL-C particles; total, large, medium and small LDL-C particles; and intermediate density lipoprotein (IDL). | Day 0, Week 2, 6 (Baseline), 10, 12 | 
| 12-Hours Fasting Lipid Profile: Level of High Density Lipoprotein Cholesterol (HDL-C) Particles | Participants were required to fast for 12 hours prior to sampling for lipid profile which included following parameters: total, large, medium and small HDL-C particles. | Day 0, Week 2, 6 (Baseline), 10, 12 | 
| Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) | DAS28-3 (CRP) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count and the CRP (milligram per liter [mg/L]). DAS28-3 (CRP) less than or equal to (<=)3.2 indicated low disease activity, DAS28-3 (CRP) more than (>) 3.2 to 5.1 indicated moderate to high disease activity. | Day 0, Week 6 (Baseline), 12 | 
| Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) | DAS28-4 (CRP) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, C-reactive protein (CRP) [mg/L] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-4 [CRP] <=3.2 indicated low disease activity, DAS28-4 [CRP] >3.2 to 5.1 indicated moderate to high disease activity and DAS28 less than 2.6 indicates remission. | Day 0, Week 6 (Baseline), 12 | 
| Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) | DAS28-3 (ESR) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]). DAS28-3 (ESR) <=3.2 indicated low disease activity, DAS28-3 (ESR) >3.2 to 5.1 indicated moderate to high disease activity. | Day 0, Week 6 (Baseline), 12 | 
| Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) | DAS28-4 (ESR) was calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) [mm/hr] and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging from 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-4 (ESR) <=3.2 indicated low disease activity, DAS28-4 (ESR) >3.2 to 5.1 indicated moderate to high disease activity. | Day 0, Week 6 (Baseline), 12 | 
| Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response | ACR20 responses were defined as greater than or equal to 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the 5 remaining ACR-core set measures: 1) physician's global assessment of disease activity, 2) participants assessment of disease activity, 3) participants assessment of pain, 4) participants assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. | Week 6 (Baseline), 12 | 
| Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response | ACR50 responses were defined as greater than or equal to 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the 5 remaining ACR-core set measures: 1) physician's global assessment of disease activity, 2) participants assessment of disease activity, 3) participants assessment of pain, 4) participants assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. | Week 6 (Baseline), 12 | 
| Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response | ACR70 responses were defined as greater than or equal to 70% improvement in tender or swollen joint counts and 70% improvement in 3 of the 5 remaining ACR-core set measures: 1) physician's global assessment of disease activity, 2) participants assessment of disease activity, 3) participants assessment of pain, 4) participants assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. | Week 6 (Baseline), 12 | 
| Tender-Joint Count | Tender joint count (TJC) is an assessment of 68 joints (upper body, upper extremity, and lower extremity). Each joint's response to pressure/motion was assessed using the following scale: Present/Absent/Not Done/Not Applicable (for artificial joints). | Day 0, Week 6 (Baseline), 12 | 
| Swollen-Joint Count | Swollen joint count (SJC): an assessment of 66 joints (upper body, upper extremity, and lower extremity). Each joint was assessed for swelling using the following scale: Present/Absent/Not Done/Not Applicable (for artificial joints). | Day 0, Week 6 (Baseline), Week 12 | 
| C-Reactive Protein (CRP) | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. Normal range is 1-3 milligram per liter (mg/L). | Day 0, Week 6 (Baseline), 12 | 
| Erythrocyte Sedimentation Rate (ESR) | ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation. | Day 0, Week 6 (Baseline), 12 | 
| Patient Assessment of Arthritis Pain | Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) visual analog scale (VAS). The scale ranged from 0 (no pain) to 100 (most severe pain), measurement on a scale corresponds to the magnitude of their pain. | Day 0, Week 6 (Baseline), 12 | 
| Physician's Global Assessment (PhysGA) of Arthritis Pain | The physician evaluated participants disease signs, functional capacity and physical examination independent of the patient's global assessment of arthritis. Physician's response was recorded using 0-100 mm visual analog scale (VAS), where 0=no pain and 100=most severe pain. | Day 0, Week 6 (Baseline), Week 12 | 
| Patient's Global Assessment (PtGA) of Arthritis Pain | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0-100 mm visual analog scale where 0=no pain and 100=most severe pain. | Day 0, Week 6 (Baseline), Week 12 | 
| Health Assessment Questionnaire Disability Index (HAQ-DI) | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 functional categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3, 0=least functional difficulty and 3=extreme functional difficulty. | Day 0, Week 6 (Baseline), 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cholesterol, lipids, rheumatoid arthritis, CP-690, 550