Long Term Safety Trial of z102 and Prednisone in Patients With Moderate to Severe Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study will compare an experimental drug called Z102 (combination of prednisolone and dipyridamole, against prednisone 5mg and prednisone 7.5mg in patients with moderate to severe Rheumatoid Arthritis for a period of 52 weeks.

Detailed Description
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This is a long-term Phase II safety study of approximately 52 weeks in duration. Eligible patients will have completed at least 6 weeks of Protocol Z102-008 and will have met all inclusion and exclusion criteria for this study. All patients will be up-titrated on Z102 over 3 weeks or will receive prednisone 5.0 mg or 7.5 mg: Primary objectives: Adverse events (AEs) Vital signs Clinical laboratory and clinical chemistry evaluations Secondary objectives: Joint imaging and bone density DAS28-CRP and individual components Patient Global Assessment of Disease Activity American College of Rheumatology criteria (ACR 20, ACR 50, ACR 70) Multidimensional Assessment of Fatigue (MAF) Time to failure

Official Title
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A Phase II, Double-blind, Controlled, Multi-center, Randomized, Long Term Safety Trial of z102 and Prednisone (5 mg or 7.5 mg) in Patients With Moderate to Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Prednisolone-Dipyridamole
* Drug: Prednisone
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have completed all 12 weeks of Protocol Z102-008 or discontinued after participating in at least 6 weeks of the randomized withdrawal portion of Z102-008 for acceptable reasons Have met all inclusion/exclusion criteria for enrollment into Protocol Z102-008 Have been on DMARD therapy for at least 90 days and have been on a stable DMARD dose without dosage adjustment or modification for 6 weeks prior to enrollment into Protocol Z102-008, and be able to maintain the same dose of conventional DMARD therapy during Protocol Z102-009 participation Exclusion Criteria: Did not complete 6 weeks of the double-blind section of Protocol Z102-008, or was discontinued from Protocol Z102-008 for reasons of an AE, protocol violation, or non-compliance Active cardiovascular disease, unless well controlled by appropriate treatment, for a minimum of 3 months prior to screening for enrollment into Protocol Z102-008 Currently taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg Taking oral steroids at a daily prednisone dose, or the equivalent, of >10 mg/day within the past 2 weeks Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering study Protocol Z102-008 or Protocol Z102-009, at any time during the study, or be anticipated to be given at any time during the study The need to continue the use of one or multiple NSAIDs at the same time, or use acetaminophen on a chronic basis All opiate use is prohibited. Use of any other medications or herbs or non-pharmacological treatments (e.g., acupuncture) used for the treatment of pain is prohibited Has, or has had, any active severe infections or recent invasive surgical procedures within 30 days of Protocol Z102-008 or Protocol Z102-009 initiation HIV, hepatitis B, or hepatitis C infection Has undergone administration of any investigational drug within 30 days of study All biologic agents are excluded for 90 days prior to Screening and during the conduct of Protocol Z102-008, and Protocol Z102-009 Has undergone administration of rituximab or any B-cell depleting investigational drugs within 6 months of Protocol Z102-008 Screening or Protocol Z102-009 initiation, or at any time during participation in study Protocol Z102-008 Has a history of hypersensitivity reaction to glucocorticoids and/or dipyridamole Known or suspected history of alcohol or drug abuse within 2 years prior to Screening for Protocol Z102-008 Has any other medical condition which may interfere with the conduct of this study in the opinion of the investigator

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: prednisolone-dipyridamole<br> | Drug: Prednisolone-Dipyridamole<br>* Oral, QD<br>* Other names: Z102;|
| Active Comparator: prednisone 5mg<br> | Drug: Prednisone<br>* Oral QD Prednisone 5mg<br>|
| Active Comparator: prednisone 7.5mg<br> | Drug: prednisone<br>* Oral, QD prednisone 7.5mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in incidence rates of adverse events between treament groups |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint imaging |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to Severe