A Study of ARRY-371797 in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This is a Phase 2 study, involving a 4-week treatment period, designed to test the ability of investigational study drug ARRY-371797 to reduce pain in patients with moderate to severe pain due to osteoarthritis (OA) of the knee, and to further evaluate the drug's safety. Approximately 150 patients from the US will be enrolled in this study.

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: ARRY-371797, p38 inhibitor; oral
* Drug: Oxycodone hydrochloride (HCl) extended release (ER), opioid agonist; oral
* Drug: Placebo; oral


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of OA of the knee, based on American College of Rheumatology (ACR) criteria, confirmed by X-ray (K-L Grade II/III within the last year). At least moderate or severe pain due to OA in one knee. On nonsteroidal anti-inflammatory drug (NSAID) 28 days previous to study start and willing to continue on NSAID throughout study. Discontinuation of opioids prior to study start. Additional criteria exist. Key Exclusion Criteria: Current or recent infection in the last 7 days; infection requiring hospitalization or parenteral antibiotics within the last 6 months; history of or currently active tuberculosis, hepatitis B or C, or human immunodeficiency virus (HIV). Surgery on the index knee within the previous 6 months. Trauma or other surgeries within the previous 8 weeks. Specific abnormal laboratory values or electrocardiogram abnormalities. Gastrointestinal surgery that may interfere with motility or absorption. On non-stable dose of bisphosphonates, or any prior denosumab or parathyroid hormone (PTH) therapies. Prior parenteral tumor necrosis factor (TNF) inhibitor or anti-nerve growth factor (NGF) therapies. Intramuscular, intravenous or oral corticosteroids within the previous 6 weeks. Intra-articular corticosteroids in the index knee within the previous 8 weeks or viscosupplementation in the index knee within the previous 4 months. Currently enrolled in or participated in another clinical trial within the previous 3 months. Additional criteria exist.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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: ARRY-371797<br> | Drug: ARRY-371797, p38 inhibitor; oral<br>* multiple dose, single schedule<br>|
| Active Comparator: Oxycodone HCl ER<br> | Drug: Oxycodone hydrochloride (HCl) extended release (ER), opioid agonist; 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 |
| --- | --- | --- |
| Assess the efficacy of the study drug (versus placebo) in terms of change from baseline to week 4 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score (index knee). |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of the study drug (versus placebo) in terms of change from baseline to week 4 in the WOMAC stiffness and physical function subscale scores (index knee). |  | 4 weeks | 
| Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests, electrocardiograms and vital signs. |  | 5 weeks | 
| Characterize the pharmacokinetics of the study drug and metabolite as determined by plasma concentrations. |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, knee, pain, NSAID