Inclusion Criteria:

1. Male or non-pregnant female subjects, 18 years and older with a history of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medical condition expected to require daily NSAID therapy for at least 6 months, with a documented history of an ulcer related serious upper gastrointestinal event such as bleeding, perforation or obstruction

2. Female subjects are eligible for participation in the study if they are of:

   • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant);

   • Childbearing potential, have a negative pregnancy test at screening, and at least one of the following applies or is agreed to by the subject:

     • 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
3. 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:

1. History of hypersensitivity to esomeprazole or to another proton-pump inhibitor
2. History of allergic reaction or intolerance to any NSAID (including aspirin) and/or a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps
3. Positive test result for H. pylori at screening
4. Participation in any study of an investigational treatment in the 4 weeks before screening
5. Presence of uncontrolled acute or chronic medical illness, e.g. gastrointestinal disorder, hypertension, diabetes, thyroid disorder, depression and/or infection that would endanger a subject if they were to participate in the study
6. Gastrointestinal disorder or surgery leading to impaired drug absorption
7. 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
8. Schizophrenia or bipolar disorder
9. Use of any excluded concomitant medication (see Section 9.2)
10. 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
11. Serious blood coagulation disorder, including use of systemic anticoagulants
12. Screening endoscopy showing >10 erosions or any gastric or duodenal ulcer at least 3 mm in diameter with depth
13. Screening laboratory ALT or AST value > 2 times the upper limit of normal
14. Estimated creatinine clearance < 50 ml/min
15. 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
16. 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