A Phase 2, Randomized, Double Blind Assessment Of Efficacy And Safety Of Pf 04171327(1, 5, 10, 15 Mg Dose, Daily) Compared To 5 Mg And 10 Mg Prednisone Daily And Placebo Daily In Subjects With Rheumatoid Arthritis Over An 8 Week Period Followed By A 4 Week Period Of Tapering Of Study Drug.
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 323
- Locations
- 91
- Primary Endpoint
- Percentage of Participants Achieving a 20% Improvement in American College of Rheumatology (ACR) Criteria at Week 8
Overview
Brief Summary
The purpose of this study is to compare the safety and efficacy of multiple doses of PF-04171327, an experimental glucocorticoid drug, to prednisone at 5 mg or 10 mg and placebo in the treatment of rheumatoid arthritis. All subjects will also be receiving background treatment of methotrexate for their rheumatoid arthritis. Study medication will be given for eight weeks followed by a 4 week period during which the dose of study medication will be gradually reduced. The efficacy of the study medications will be determined by assessing severity of the rheumatoid arthritis during the study and safety will be determined by adverse event reporting, laboratory tests and biomarker analysis.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects must have documented rheumatoid arthritis with a duration of at least 3 months as determined by the investigator using standardly accepted criteria, must have been receiving methotrexate for at least 3 months to treat their rheumatoid arthritis, and must be free of any signs or symptoms of infection.
Exclusion Criteria
- •Subjects cannot enter the study if they have recently received treatment with certain medications which might interfere with study medications;
- •subjects cannot enter if they have abnormalities in certain blood tests, history of cancer, recent bone fracture or other significant conditions.
Arms & Interventions
PF-04171327 1 mg QD
Intervention: PF-04171327 (Drug)
PF-04171327 5 mg QD
Intervention: PF-04171327 (Drug)
PF-04171327 10 mg QD
Intervention: PF-04171327 (Drug)
PF-04171327 15 mg QD
Intervention: PF-04171327 (Drug)
prednisone 5 mg QD
Intervention: prednisone (Other)
prednisone 10 mg QD
Intervention: prednisone (Other)
placebo
Intervention: placebo (Other)
Outcomes
Primary Outcomes
Percentage of Participants Achieving a 20% Improvement in American College of Rheumatology (ACR) Criteria at Week 8
Time Frame: Week 8
ACR20 response: greater than or equal to (≥) 20 percent (%) improvement in 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).
Mean Percent Change From Baseline in 0 Hour Procollagen Type 1 N Terminal Propeptide (P1NP) at Week 8 (Comparisons to Prednisone 5 mg)
Time Frame: Week 8
Change from baseline in P1NP at week 8 is presented in this outcome measure.
Mean Percent Change From Baseline in 0 Hour Urinary N Telopeptide/Urinary Creatinine (uNTx/uCr) at Week 8 (Comparisons to Prednisone 5 mg)
Time Frame: Week 8
Change from baseline in uNTx/uCr at week 8 is presented in this outcome measure.
Secondary Outcomes
- Percentage of Participants Achieving ACR20 Response at Weeks 2, 4, and 12 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, and 12 (taper period))
- Change From Baseline in Tender-Joint Counts at Weeks 2, 4, 6, 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Percentage of Participants Achieving ACR50 Response at Weeks 2, 4, 6, 8 and 12 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, 8, and 12 (taper period))
- Percentage of Participants Achieving ACR70 Response at Weeks 2, 4, 6, 8 and 12 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, 8, and 12 (taper period))
- Change From Baseline in Tender-Joint Counts at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in Swollen-Joint Counts at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in Swollen-Joint Counts at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in C Reactive Protein (CRP) at Weeks 2, 4, 6, and 8 (Comparisons to Placebo and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline of CRP at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in Patient Global Assessment of Arthritis at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in Patient Global Assessment of Arthritis at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in Physician Global Assessment of Arthritis at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in Physician Global Assessment of Arthritis at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in Pain VAS at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in Pain VAS at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in HAQ-DI at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in HAQ-DI at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in Disease Activity Score (DAS) 28-3 CRP at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in DAS 28-3 CRP at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in DAS28-4(CRP) at Weeks 2, 4, 6, and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 2, 4, 6, and 8)
- Change From Baseline in DAS28-4(CRP) at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in SF-36v2 Mental Component Scores at Weeks 4 and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 4 and 8)
- Change From Baseline in SF-36v2 Mental Component Scores at Week 12 (Descriptive Statistics)(Week 12)
- Change From Baseline in SF-36v2 Physical Component Scores at Weeks 4 and 8 (Comparisons to Placebo, and Prednisone 10 mg)(Weeks 4 and 8)
- Change From Baseline in SF-36v2 Physical Component Scores at Week 12 (Descriptive Statistics)(Week 12)