Rates of Gastric Ulcer by Endoscopy in Knee Osteoarthritis Patients Receiving LT-NS001 Versus Naprosyn®

Study Overview
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Brief Summary
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LT-NS001 is a prodrug of Naproxen, which is inactive as a cox inhibitor while intact and is rapidly metabolized to Naproxen once absorbed. This trial will compare the rate of gastric ulcer by endoscopy over three months in patients with knee osteoarthritis, with patients receiving either LT-NS001 at a dose which provides comparable dose levels of Naproxen, or Naprosyn® 500mg (an approved treatment for OA).

Detailed Description
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This is a double-blind, double-dummy, active-comparator study of LT-NS001 versus Naprosyn® for 12 weeks in patients aged 45-80 with osteoarthritis of the knee who are candidates for ongoing NSAID therapy. The percentage of patients with a gastric ulcer by endoscopy (EGD) at week 12 will be compared. EGD is performed at screening and months 1, 2, and 3. Secondary objectives include assessment of pain in the affected knee by WOMAC questionnaire to demonstrate non-inferior pain control using LT-NS001 as compared to Naprosyn®. Information about gastrointestinal pain and tolerability will be collected. The length of the study is up to 19 weeks with a 2-3 week screening period, a 12 week treatment period and a 4 week post treatment monitoring period.

Official Title
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A Double-Blind, Double-Dummy, Randomized, Active-Comparator, Non-Inferiority Study of LT-NS001 Versus Naprosyn® for Twelve Weeks in Osteoarthritis Patients to Compare Endoscopic Gastric Ulcer Rates

Conditions
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Osteoarthritis

Intervention / Treatment
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* Drug: LT-NS001
* Drug: Naprosyn®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthritis of knee Appropriate candidate for chronic NSAID therapy due to moderate or severe pain on most days in the 28 days before screening for study. Exclusion Criteria: Pregnant/Nursing women History of GI bleeding, perforation or obstruction A documented symptomatic GI ulcer during past 5 years Presence of GI ulcer or more than 2 erosions on screening endoscopy Allergy to naproxen (or naproxen intolerance), acetylsalicylic acid, or other NSAID drug

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 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: LT-NS001<br>LT-NS001 1200 mg b.i.d. p.o. for 12 weeks | Drug: LT-NS001<br>* 1200 mg b.i.d. p.o. for 12 weeks<br>|
| Active Comparator: Naprosyn®<br>Naprosyn® 500 mg b.i.d for 12 weeks | Drug: Naprosyn®<br>* 500 mg b.i.d. p.o. for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric Ulcer by Endoscopy |  | Baseline, Day 29, Day 57 and Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score |  | Screening, Baseline, Days 15, 29, 57 and 85 | 
| Population pharmacokinetic analysis will assess the influence of covariates on the absorption/metabolism of LT-NS001 to naproxen |  | Two separate days after Day 14, at least two weeks apart | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LT-NS001, Gastric Ulcers, NSAID, Osteoarthritis, Naproxen