Evaluation of 2 Oral Doses of PG-760564 in Rheumatoid Arthritis (RA) Patients Receiving Methotrexate

Study Overview
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Brief Summary
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This will be a 12-week, double-blind, randomized, placebo-controlled, parallel group, multicenter study to evaluate the safety, efficacy, and PK of oral administration of PG-760564 in adult patients with active RA receiving treatment with MTX. Two oral doses of PG-760564 will be evaluated: 25 mg BID and 100 mg BID. The study will consist of a screening visit followed by a washout period for all disease modifying antirheumatic drugs (DMARDs) and anti-cytokine therapies except MTX. After the washout period, patients determined to be eligible will be randomized to receive either 25 mg BID or 100 mg BID of oral PG-760564, or placebo for 12 weeks. There will be 6 treatment visits and a follow-up visit 4 weeks after the last treatment visit. The primary efficacy endpoint will be the proportion of patients meeting the ACR 20 response criteria after 12 weeks of treatment.

Detailed Description
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The study will be conducted in North America and Europe at approximately 50 to 60 sites. Approximately 270 patients will be randomized, of which 189 are expected to complete the study. The study will consist of a screening visit followed by a washout period for all disease modifying antirheumatic drugs (DMARDs) and anti-cytokine therapies except MTX. The washout period will be 4 weeks for sulfasalazine, hydroxychloroquine, azathioprine, D-penicillamine, etanercept, and anakinra, 8 weeks for gold, infliximab, and adalimumab, and 12 weeks for abatacept. After the washout period, the patients determined to be eligible will be randomized to receive either 25 mg BID or 100 mg BID of oral PG-760564, or placebo for 12 weeks. There will be 6 treatment visits (Weeks 1, 2, 4, 6, 8, and 12) and a follow-up visit 4 weeks after the last treatment visit (Week 16). Patients will not initiate new therapies until after the 4-week follow-up is completed. Liver function tests will be evaluated at every visit. The primary efficacy endpoint will be the proportion of patients meeting the ACR 20 response criteria after 12 weeks of treatment.

Official Title
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A Multicenter, Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of 2 Oral Doses, 25 mg Twice Daily and 100 mg Twice Daily, of PG-760564 in Adult Patients With RA Receiving Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: PG-760564
* Drug: Placebo dose
* Drug: PG-760564


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet American College of Rheumatology (ACR) criteria for Rheumatoid Arthritis Disease duration of at least 6 months Must be treated with Methotrexate for at least 24 weeks At least 6 swollen joints and 6 tender joints Washout required for other Disease Modifying Anti-rheumatic Drugs (DMARDs) Women of childbearing age and all males must use acceptable method of birth control Exclusion Criteria: Tuberculosis Malignancies Abnormal electrocardiograms as described in the protocol Current infection or recurrent infections or immunodeficiency Liver diseases and abnormalities in liver function tests as described in the protocol Autoimmune diseases other than RA except Sjogren's syndrome secondary to RA; History of demyelization diseases Any condition that in the opinion of the investigator could be detrimental to patients enrolling in the study including clinically important changes in laboratory values and other diseases described in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, oral dose, BID | Drug: Placebo dose<br>* placebo, BID, oral for 12 weeks<br>|
| Experimental: 25 mg PG-760564<br>25 mg BID, of oral PG-760564 | Drug: PG-760564<br>* 25 mg BID, of oral PG-760564<br>|
| Experimental: 100 mg PG-760564<br>100 mg BID, of oral PG-760564 | Drug: PG-760564<br>* 100 mg BID, of oral PG-760564<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Meeting American College of Rheumatology 20 Response Criteria (ACR20) at 12weeks | percent, relative to baseline, of patients meeting the American College of Rheumatology 20 response criteria (ACR20) at 12weeks | 12 weeks |