A Study of ARRY-371797 in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This is a Phase 1 study, involving a 29-day treatment period, designed to evaluate the pharmacokinetics and the effectiveness of investigational study drug ARRY-371797 in treating rheumatoid arthritis in patients receiving stable doses of methotrexate, and to further evaluate the drug's safety. Approximately 30 patients from the US will be enrolled in this study.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: ARRY-371797, p38 inhibitor; oral
* Drug: Placebo; oral


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosed with rheumatoid arthritis (RA) at least 3 months prior to study start based upon the American College of Rheumatology (ACR) 1987 Revised Criteria. On a stable weekly dose of both methotrexate (MTX) (10 - 25 mg/week inclusively; either oral or parenteral) and folate (≥ 5 mg weekly ) for ≥ 6 weeks prior to study start and is willing to continue on these regimens for the duration of the study. Meets the ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II, or III. Completed an appropriate washout period if treated with specified therapies. Patients may continue on specified stable background therapy for RA (doses should be stable for at least 6 weeks prior to the first dose of study drug, unless the patient stops due to documented disease improvement, with Sponsor approval). Additional criteria exist. Key Exclusion Criteria: Diagnosis of any other inflammatory or non-inflammatory arthritis (e.g. spondyloarthritis; fibromyalgia, psoriatic arthritis, crystal-proven gout) that may interfere with disease activity assessments and/or clinically apparent osteoarthritis which would affect subsequent efficacy measures. Has received any of the following prior treatments: Within 4 weeks of first dose of study drug: anakinra (Kineret®), etanercept (Enbrel®); Within 8 weeks of first dose of study drug: infliximab (Remicade®), adalimumab (Humira®), leflunomide (Arava®); At any time: rituximab (Rituxan®), alemtuzumab (CamPath®), any experimental B cell targeting agents. Treatment with potent CYP3A inhibitors or inducers, disease-modifying antirheumatic drugs (DMARDs) and/or biologic response modifiers (BRMs) during the study. Additional criteria exist.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARRY-371797 (Schedule 1)<br> | Drug: ARRY-371797, p38 inhibitor; oral<br>* multiple dose, single schedule<br>|
| Experimental: ARRY-371797 (Schedule 2)<br> | Drug: ARRY-371797, p38 inhibitor; oral<br>* multiple dose, single schedule<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo; oral<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the pharmacokinetics (PK) of the study drug and a metabolite in terms of plasma concentrations. |  | 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests, vital signs and electrocardiograms. |  | 29 days | 
| Assess the efficacy of study drug (versus placebo) in terms of cross-reactive protein (CRP), the Patient's Assessment of Arthritis Pain (100 mm visual analog scale [VAS]) and urinary N-Telopeptide Cross-Links (NTx). |  | 29 days |