A Phase II, Double-Blind, Placebo-Controlled, Multi-Center, Randomized Withdrawal Design Trial Using Adaptive Randomization Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis
Overview
- Phase
- Phase 2
- Intervention
- Prednisolone
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Zalicus
- Enrollment
- 294
- Locations
- 1
- Primary Endpoint
- Change From Baseline in DAS28-CRP at 12 Weeks
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis.
Detailed Description
The primary objective of the study was to demonstrate the efficacy of Z102 (2.7 mg prednisolone/360 mg dipyridamole) versus placebo on the Disease Activity Score 28 using C reactive protein (DAS28-CRP) in subjects with rheumatoid arthritis at the study endpoint of 12 weeks
Investigators
Eligibility Criteria
Inclusion Criteria
- •Meet the ACR / EULAR criteria for classification of RA
- •Have moderate to severe RA, defined as involving a minimum (≥6 total swollen and ≥6 total tender) of the 28 joints assessed
- •Have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score ≥4.5
- •Have been on a stable dose of conventional DMARD therapy for at least 90 days without dosage adjustment or modification and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy
Exclusion Criteria
- •Treatment-refractory patients are excluded
- •Has active cardiovascular disease, unless well controlled by appropriate treatment for a minimum of 3 months prior to screening
- •Is taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg
- •Is currently taking steroids at a daily prednisone dose, or the equivalent, of \>10 mg
- •Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study
- •The need to continue the use of one or multiple NSAID's at the same time, or the use of acetaminophen on a chronic basis
- •All opiate use is prohibited
- •Use of any other medications or herbs used for the treatment of pain is prohibited
- •Patients with a history of or currently active tuberculosis as per specific country guidelines are excluded
- •Has uncontrolled diabetes mellitus as defined by a serum glucose \>126 mg/dl
Arms & Interventions
Prednisolone
Prednisolone 2.7 mg daily for 12 weeks
Intervention: Prednisolone
dipyridamole
Dipyridamole 360 mg daily for 12 weeks
Intervention: dipyridamole
prednisone
Prednisone 5 mg daily for 12 weeks
Intervention: Prednisone
Z102 (2.7/360)
Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks
Intervention: Z102
placebo
Placebo daily for 12 weeks
Intervention: placebo
Outcomes
Primary Outcomes
Change From Baseline in DAS28-CRP at 12 Weeks
Time Frame: baseline to week 12
The primary efficacy endpoint was the mean change in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12. The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of \<3.2 suggests a low level of disease activity, while a score of \>5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores.
Secondary Outcomes
- Multidimensional Assessment of Fatigue (MAF) at Week 12(week 12)
- Time to Failure (Days)(Baseline to 12 weeks)
- Change From Baseline in DAS28-CRP Individual Components at 12 Weeks(Baseline to week 12)
- Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks(Week 12)