Official Title: “A 6-Month, Phase 3, Randomized, Double-Blind, Parallel-Group, Controlled, Multi-Center Study to Evaluate the Incidence of Gastric Ulcers Following Administration of Either PN 200 or Naproxen in Subjects Who Are at Risk for Developing NSAID-Associated Ulcers.”

The purpose of this study is to evaluate the incidence of gastric ulcers following administration of either PN 200 or Naproxen in subjects who are at risk for developing NSAID-associated ulcers.

Study Type: Interventional

Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2007

Intervention(s) in this Clinical Trial

• Drug: PN 200 tablets (500 mg naproxen and 20 mg omeprazole)
• Drug: Naproxen 500 mg tablets (PN 200 minus omeprazole)

Primary Measures

• The primary efficacy variable is the incidence of gastric ulcers, defined as a mucosal break of at least 3 mm in diameter (measured by close application of open endoscopic biopsy forceps) with depth, at anytime throughout 6 months of study treatment.

Secondary Measures

• The secondary efficacy variable is the incidence of duodenal ulcers at any time throughout 6 months of treatment, tolerability and safety.

Inclusion Criteria:

• Male or non-pregnant female subjects with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical conditions expected to require daily NSAID therapy for at least 6 months who are 18-49 years of age and have a history of a documented, uncomplicated gastric or duodenal ulcer (a mucosal break of at least 3 mm in diameter with depth, without any concurrent bleeding, clot or perforation) within the past 5 years OR, who are 50 years of age and older (these subjects do not require a history of a documented, uncomplicated gastric or duodenal ulcer within the past 5 years).
• Female subjects are eligible for participation in the study if they are of:
• 1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, 2. Childbearing potential, have a negative pregnancy test (urine) at screening, and at least one of the following applies or is agreed to by the subject:
• Complete abstinence from intercourse for at least 14 days prior to first dose of study drug, throughout the study, and for 30 days after completion of the study
• Female sterilization or sterilization of male partner; or,
• Hormonal contraception by oral route, implant, injectable, vaginal ring;
• or,
• Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year;
• Double barrier method (2 physical barriers or 1 physical barrier plus spermicide); or
• Any other method with published data showing that the lowest expected failure rate is less than 1% per year.
• Each subject must be able to understand and comply with study procedures required of a subject and is able and willing to provide written informed consent prior to any study procedures being performed.

Exclusion Criteria:

• History of hypersensitivity to omeprazole or to another proton-pump inhibitor.
• History of allergic reaction or intolerance to any NSAID (including aspirin) and/or subject has a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps.
• Participation in any study of an investigational treatment in the 4 weeks before screening.
• Presence of uncontrolled acute or chronic medical illness, e.g. gastrointestinal disorder, diabetes, hypertension, thyroid disorder, depression and/or infection that would endanger a subject if they were to participate in the study.
• Gastrointestinal disorder or surgery leading to impaired drug absorption.
• Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the investigator's opinion would endanger a subject if they were to participate in the study.
• Schizophrenia or bipolar disorder.
• Use of any excluded concomitant medication (see Section 9.2).
• A recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse/abuse of narcotics for management of pain.
• Serious blood coagulation disorder including use of systemic anticoagulants.
• Positive test result for H. pylori at screening.
• Baseline endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter with depth.
• Screening laboratory value for ALT, AST >2 times the upper limit of normal.
• Estimated creatinine clearance < 30 ml/min.
• Other than noted specifically, any screening laboratory value that is clinically significant in the investigator's opinion and would endanger a subject if they were to participate in the study.
• History of malignancy, treated or untreated, within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Pozen

Information obtained from ClinicalTrials.gov on October 06, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00367211

Study ID Number: PN200-301

ClinicalTrials.gov Identifier: NCT00367211

Health Authority: United States: Food and Drug Administration