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

• ClinicalTrials.gov Identifier: NCT01059864
• Recruitment Status: Completed
• First Posted: February 1, 2010
• Results First Posted: December 13, 2012
• Last Update Posted: December 13, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 28, 2010
• First Posted Date: February 1, 2010
• Results First Submitted Date: November 14, 2012
• Results First Posted Date: December 13, 2012
• Last Update Posted Date: December 13, 2012
• Study Start Date: February 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2012): Percent Change From Baseline (Week 6) in Low Density Lipoprotein-Cholesterol (LDL-C) Level at Week 12 [ Time Frame: Baseline (Week 6), Week 12 ]
• Original Primary Outcome Measures (submitted: January 28, 2010): Percent change in LDL level compared to baseline (Wk 6) [ Time Frame: Week 12 ]

Current Secondary Outcome Measures (submitted: November 14, 2012)

• Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline (Week 6), Week 12 ]
• 12-Hours Fasting Lipid Profile [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ]
  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.
• 12-Hours Fasting Lipid Profile: Particle Size of Lipoproteins [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ]
  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.
• 12-Hours Fasting Lipid Profile: Level of Lipoprotein Particles [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ]
  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).
• 12-Hours Fasting Lipid Profile: Level of High Density Lipoprotein Cholesterol (HDL-C) Particles [ Time Frame: Day 0, Week 2, 6 (Baseline), 10, 12 ]
  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.
• Disease Activity Score Using 28-Joint Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.
• Disease Activity Score Using 28-Joint Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.
• Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.
• Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.
• Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 6 (Baseline), 12 ]
  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.
• Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 6 (Baseline), 12 ]
  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.
• Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 6 (Baseline), 12 ]
  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.
• Tender-Joint Count [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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).
• Swollen-Joint Count [ Time Frame: Day 0, Week 6 (Baseline), Week 12 ]
  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).
• C-Reactive Protein (CRP) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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).
• Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.
• Patient Assessment of Arthritis Pain [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.
• Physician's Global Assessment (PhysGA) of Arthritis Pain [ Time Frame: Day 0, Week 6 (Baseline), Week 12 ]
  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.
• Patient's Global Assessment (PtGA) of Arthritis Pain [ Time Frame: Day 0, Week 6 (Baseline), Week 12 ]
  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.
• Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Day 0, Week 6 (Baseline), 12 ]
  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.

Original Secondary Outcome Measures (submitted: January 28, 2010)

• Absolute change in LDL level compared to baseline (Week 6) [ Time Frame: Week 12 ]
• 12-hour fasting lipids, including but not limited to total cholesterol, LDL C, HDL C, VLDL C, non HDL C, apolipoproteins A 1 and B, lipoprotein particle size and pool size and triglycerides [ Time Frame: At each timepoint ]
• RA related efficacy endpoints including DAS28 3 and DAS28 4 (CRP and ESR), ACR response rates and their components: joint counts, HAQ DI, patient & physician VAS scales, CRP and ESR [ Time Frame: Pretreatment, Wk 6 and Wk 12 ]
• Clinical safety laboratory testing (hematology, chemistry, urinalysis), physical exam and vital signs (complete & targeted physical examination, electrocardiogram, blood pressure and temperature), and assessment of adverse events [ Time Frame: At each timepoint ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Of The Effects Of Atorvastatin On Cholesterol Levels In Rheumatoid Arthritis Patients Taking CP-690,550
• Official Title: Phase 2 Study Of The Effects Of Open-Label CP-690,550 And Double-Blind Atorvastatin On Lipids In Patients With Active Rheumatoid Arthritis
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

• Drug: CP-690,550
  12 week open-label CP-690,550 10 mg oral tablets administered twice daily starting at Day 0 through Week 12
• Drug: Atorvastatin
  Starting at Week 6 and continuing through Week 12 atorvastatin 10 mg oral tablets administered once daily
• Drug: Atorvastatin Placebo
  Starting at Week 6 and continuing through Week 12 atorvastatin placebo tablets administered once daily

Study Arms

• Experimental: Arm 1
  Interventions:

  • Drug: CP-690,550
  • Drug: Atorvastatin
• Experimental: Arm 2
  Interventions:

  • Drug: CP-690,550
  • Drug: Atorvastatin Placebo

Publications *

• Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
• Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;:
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
• McInnes IB, Kim HY, Lee SH, Mandel D, Song YW, Connell CA, Luo Z, Brosnan MJ, Zuckerman A, Zwillich SH, Bradley JD. Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study. Ann Rheum Dis. 2014 Jan;73(1):124-31. doi: 10.1136/annrheumdis-2012-202442. Epub 2013 Mar 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 14, 2012): 111
• Original Estimated Enrollment (submitted: January 28, 2010): 100
• Actual Study Completion Date: November 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of, United States

Administrative Information

• NCT Number: NCT01059864
• Other Study ID Numbers: A3921109
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2012