Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers in High Risk Subjects Compared to Arthrotec
Condition: Gastric Ulcer
MeSH terms: Stomach Ulcer; Ulcer
Intervention: PN400 (VIMOVO); Diclofenac/Misoprostol
Intervention description: PN400 tablet (500 mg delayed-release naproxen/20 mg immediate-release esomeprazole) given by mouth twice daily (bid).; Over-encapsulated ARTHROTEC® 75 (75 mg diclofenac sodium/200 mcg misoprostol) capsules given by mouth bid.
Intervention MeSH terms: Diclofenac; Arthrotec; Misoprostol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSAID; Gastric Ulcer; High risk; Arthrotec; Vimovo

Summary:

      This randomized, double-blind, parallel-group, controlled, multi-center clinical trial of 6
      months duration is designed to assess the efficacy, tolerability and safety of PN400 versus
      diclofenac/misoprostol in subjects at high risk for developing NSAID-associated gastric
      ulcers. Approximately 100 sites will participate to enroll a total of 200 subjects (100 per
      arm).

      At least 20% of the subjects enrolled will be age 65 years and older.
    

Eligibility criteria:

        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