To Assess the Effect of Naproxcinod Versus Naproxen and Ibuprofen on Arterial Blood Pressure in Osteoarthritis Patients With Controlled Essential Hypertension

Study Overview
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Brief Summary
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To assess the effect of naproxcinod vs. naproxen and ibuprofen on arterial blood pressure in patients with osteoarthritis and controlled essential hypertension

Detailed Description
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This is a 16-week, randomized, double-blind, multicenter study comparing the effect of naproxcinod, naproxen, and ibuprofen on 24 hour arterial blood pressure profile. Patients will be randomly allocated to naproxcinod 375mg, naproxcinod 750mg, naproxen 250mg, naproxen 500mg, or ibuprofen 600mg in a 1:1:1:1:1 ratio.

Official Title
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A 16-week, Phase 1, Multicenter, Double-Blind, Randomized, Naproxen and Ibuprofen-controlled, Parallel-Group Pharmacological Study, to Assess the Effect of Naproxcinod (375mg and750mg, Bid) Compared to Doses of Naproxen (250mg and 500mg, Bid) and to Ibuprofen (600mg, Tid) on Arterial Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring in Osteoarthritis Patients With Controlled Essential Hypertension.

Conditions
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Osteoarthritis, Hypertension

Intervention / Treatment
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* Drug: naproxcinod 375 mg bid
* Drug: naproxcinod 750 mg bid
* Drug: naproxen 250 mg bid
* Drug: naproxen 500 mg bid
* Drug: ibuprofen 600 mg tid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men/Women, 40 or older, diagnosed with hip or knee osteoarthritis. Hypertensive Patient with treated and controlled essential hypertension. Must receive at least one antihypertensive treatment from the following drug classes: Diuretic, Angiotensin-Converting Enzyme (ACE) inhibitor, Angiotensin Receptor Blockers (ARB) or Beta-Blocker (BB). Must be current chronic user of NSAIDS or acetaminophen. Must discontinue all analgesic therapy at Screening. Exclusion Criteria: More than two different classes of antihypertensive drugs. Uncontrolled diabetes. Hepatic or renal impairment. A history of alcohol/drug abuse. Diagnosis of gastric or duodenal ulceration and/or history of significant gastro-duodenal bleeding. History of congestive heart failure. Clinically relevant abnormal ECG. Current or history of a medical disease that could interfere with the study objectives or put the patient's safety at risk. Current or expected use of anticoagulants. Participation within 30 days prior to pre-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: Double


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>|
| Active Comparator: naproxen 250 mg bid<br> | Drug: naproxen 250 mg bid<br>* naproxen 250 mg bid<br>|
| Active Comparator: ibuprofen 600 mg tid<br> | Drug: ibuprofen 600 mg tid<br>* ibuprofen 600 mg tid<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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the 24-hour arterial blood pressure profile of naproxcinod, compared to naproxen as measured by ABPM, through assessing the mean change from baseline in patients with OA and controlled essential hypertension. |  | 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize the 24-hour arterial blood pressure profile of naproxcinod compared to ibuprofen as measured by ABPM, through assessing the mean change from baseline in patients with osteoarthritis and controlled essential hypertension. |  | 15 weeks | 
| To assess the general safety and tolerability of naproxcinod compared to naproxen and ibuprofen. |  | 15 weeks |