Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers in High Risk Subjects Compared to Arthrotec

Inclusion Criteria:

1. Male or non-pregnant female subjects, 18 years and older with a history ofosteoarthritis, rheumatoid arthritis, ankylosing spondylitis or other medicalcondition expected to require daily NSAID therapy for at least 6 months, with adocumented history of an ulcer related serious upper gastrointestinal event such asbleeding, 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 becomingpregnant);

• Childbearing potential, have a negative pregnancy test at screening, and at leastone 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 lowestexpected failure rate is less than 1% per year;

• Double barrier method (2 physical barriers or 1 physical barrier plusspermicide); or

• Any other method with published data showing that the lowest expectedfailure rate is less than 1% per year

3. Each subject must be able to understand and comply with study procedures required of asubject and is able and willing to provide written informed consent prior to any studyprocedures 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 ahistory 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 beforescreening

5. Presence of uncontrolled acute or chronic medical illness, e.g. gastrointestinaldisorder, hypertension, diabetes, thyroid disorder, depression and/or infection thatwould 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 inthe investigator's opinion would endanger a subject if they were to participate in thestudy

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 ordependence, 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 3mm 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 clinicallysignificant in the investigator's opinion and would endanger a subject if they were toparticipate in the study

16. History of malignancy, treated or untreated, within the past 5 years, with theexception of successfully treated basal cell or squamous cell carcinoma of the skin