Evaluating PN 400 (VIMOVO) in Reducing Gastric Ulcers Compared to Non-steroidal Antiinflammatory Drug (NSAID) Naproxen
Condition: Gastric Ulcer
MeSH terms: Stomach Ulcer; Ulcer
Intervention: PN400 (VIMOVO); Naproxen
Intervention description: PN400 tablets (Naproxen 500 mg and Esomeprazole 20 mg) twice daily (bid) taken orally.; Naproxen 500 mg dosed twice daily (bid) orally
Intervention MeSH terms: Naproxen
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 420.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSAID; gastric ulcers; Vimovo; Esomeprazole; Naproxen

Summary:

      This study uses a randomized, double-blind, controlled design to demonstrate that PN400
      (esomeprazole and naproxen) is more effective in reducing the occurrence of gastroduodenal
      ulcers, dyspepsia, and heartburn in subjects at risk for developing NSAID-associated gastric
      ulcers compared to naproxen alone.
    

Eligibility criteria:

        Inclusion Criteria

        A subject was eligible for inclusion in this study if all of the following criteria
        applied:

          1. Male or non-pregnant, non-breastfeeding 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 were

               -  18-49 years of age and had 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
                  were

               -  50 years of age and older (These subjects did not require a history of a
                  documented, uncomplicated gastric or duodenal ulcer within the past 5 years.)

          2. Female subjects were eligible for participation in the study if they were of

               -  non-childbearing potential (i.e., physiologically incapable of becoming
                  pregnant);

               -  childbearing potential, had a negative pregnancy test at Screening, and at least
                  1 of the following applied or was agreed to by the subject:

               -  Female sterilization or sterilization of male partner

               -  Hormonal contraception by oral route, implant, injectable, vaginal ring

               -  Any intrauterine device with published data showing that the lowest expected
                  failure rate is < 1% per year

               -  Double barrier method (2 physical barriers or 1 physical barrier plus spermicide)

               -  Any other method with published data showing that the lowest expected failure
                  rate is < 1% per year

          3. Each subject was required to understand and comply with study procedures required of a
             subject and was able and willing to provide written informed consent prior to any
             study procedures being performed.

        Exclusion Criteria

        A subject was not eligible for this study if any 1 or more of the following criteria
        applied:

          1. History of hypersensitivity to esomeprazole or to another PPI

          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. Participation in any study of an investigational treatment in the 4 weeks before
             Screening

          4. Presence of uncontrolled acute or chronic medical illness, e.g., GI disorder,
             hypertension, diabetes, thyroid disorder, depression and/or infection that would have
             endangered a subject if they were to have participated in the study

          5. GI disorder or surgery leading to impaired drug absorption

          6. Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in
             the investigator's opinion would have endangered a subject if they were to have
             participated in the study

          7. Schizophrenia or bipolar disorder

          8. Use of any excluded concomitant medication (see Section 9.4.8)

          9. 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

         10. Serious blood coagulation disorder, including use of systemic anticoagulants

         11. Positive test result for H. pylori at Screening

         12. Screening endoscopy showing any gastric or duodenal ulcer at least 3 mm in diameter
             with depth

         13. Screening laboratory alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) value > 2 times the upper limit of normal

         14. Estimated creatinine clearance < 30 ml/min

         15. Other than noted specifically, any screening laboratory value that was clinically
             significant in the investigator's opinion and would have endangered a subject if they
             were to have participated 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