Efficacy and Safety Study of Naproxcinod in Subjects With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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To study of efficacy and safety of Naproxcinod vs. Naproxen and Placebo in the indication of signs and symptoms of osteoarthritis

Detailed Description
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This is a 53 week study consisting in a 26 week randomized, double-blind, parallel group, multicenter study comparing efficacy and safety of Naproxcinod, Placebo and Naproxen. The first 26 weeks will be followed by a naproxen-controlled treatment period up to 52 weeks and a 1-week post-treatment safety follow-up.

Official Title
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A Phase 3, 53 Weeks Study on Analgesic Efficacy and Safety of Naproxcinod (HCT 3012): 26-Week, Randomized, Parallel-Group, Double-Blind, Placebo (13 Weeks)- and Naproxen (26 Weeks)-Controlled, Multicenter Study of Naproxcinod (375 mg Bid and 750 mg Bid) With a 26-Week Naproxen-Controlled Safety Follow-up in Subjects With Osteoarthritis of the Knee, and a 1-week Post-treatment Safety Follow-up

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: Naproxcinod 375 mg bid
* Drug: Naproxcinod 750 mg bid
* Drug: Naproxen 500 mg bid
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Woman (40 or older) with a diagnosis of primary OA of the knee. Must be a current chronic user of NSAIDS or acetaminophen Must discontinue all analgesic therapy at Screening Exclusion Criteria: Uncontrolled Hypertension or Diabetes Hepatic or Renal Impairment Current or expected use of anti-coagulant Clinical relevant abnormal ECG A history of alcohol or drug abuse Candidates for imminent joint replacement Participation within 30 days prior to screening in another investigational study

Ages Eligible for Study
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Minimum Age: 40 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: naproxcinod 375 mg bid<br> | Drug: Naproxcinod 375 mg bid<br>* Naproxcinod 375 mg bid<br>|
| Experimental: naproxcinod 750 mg bid<br> | Drug: Naproxcinod 750 mg bid<br>* Naproxcinod 750 mg bid<br>|
| Active Comparator: naproxen 500 mg bid<br> | Drug: Naproxen 500 mg bid<br>* Naproxen 500 mg bid<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To show that both doses of Naproxcinod (375 mg twice daily [bid] and 750 mg bid) were superior to placebo in relieving osteoarthritis (OA) signs and symptoms in subjects with OA of the knee at Week 13. |  | 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of naproxcinod compared to naproxen 500 mg bid in relieving OA signs and symptoms in subjects with OA of the knee |  | 52 weeks | 
| To evaluate the effect on blood pressure (BP) of both doses of naproxcinod, placebo, and naproxen 500 mg bid, as measured by the office BP monitoring in a population of OA subjects |  | 52 weeks | 
| To obtain information regarding the pharmacokinetics/exposure of both doses of naproxcinod through a population pharmacokinetics (PK) approach |  | 52 weeks | 
| To assess if there were any radiological changes at Week 52 in naproxcinod compared with naproxen subjects (target joint radiographs were taken at Screening and after 52 weeks of treatment, or if early termination occurred after Week 26) |  | 52 weeks | 
| To compare the general safety and tolerability of both doses of naproxcinod versus naproxen 500 mg bid up to 52 weeks and with one Week post treatment follow up (Week 53) |  | 53 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Degenerative