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.

• Osteoarthritis
• Rheumatoid Arthritis
• Ankylosing Spondylitis

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

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.