Study to Evaluate the Long-Term Safety of PA32540 in Subjects Who Are at Risk for Developing Aspirin-Associated Gastric Ulcers
Condition: Aspirin-Associated Gastric Ulcers
MeSH terms: Stomach Ulcer; Ulcer
Intervention: PA32540
Intervention description: PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole to be taken by mouth once daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 380.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Subjects Who are at Risk for Developing Aspirin-ASA; Subject must have a pre-existing condition for which aspirin is already indicated; Gastric Ulcers

Summary:

      This study uses an open-label design and will be conducted in approximately 40 sites in the
      United States. Approximately 400 subjects will be enrolled in the study to ensure that
      approximately 300 subjects will have 6 months exposure to PA32540 and at least 100 subjects
      will have 12 months exposure to PA32540.
    

Eligibility criteria:

        Inclusion criteria:

          1. A. Male or non-pregnant, non-breastfeeding females who have been on daily aspirin 325
             mg for at least three months and who are expected to use daily aspirin 325 mg for at
             least six months (Daily is defined as "at least 5 days per week"):

             AND, who are

               -  55 years of age and older; or

               -  18 - 54 years of age and have a history of a documented gastric or duodenal ulcer
                  within the past five years.

          2. A. Aspirin use should be for the secondary prevention of cardiovascular or
             cerebrovascular events as defined as follows:

             Have been diagnosed with or have had a history of

               -  MI (myocardial infarction that has been confirmed or suspected)

               -  Ischemic stroke

               -  TIA (transient ischemic attack)

             Or have established, clinically significant coronary and other atherosclerotic
             vascular disease (meaning at high risk for surgical intervention or for MI, TIA,
             stroke, if left untreated), including:

               -  Angina (stable or unstable)

               -  Peripheral arterial disease

               -  Atherosclerotic aortic disease

               -  Carotid artery disease Or have had

               -  CABG (coronary artery bypass graft)

               -  PCI (percutaneous coronary intervention with or without stent)

               -  Carotid endarterectomy

          3. A. If female, subjects are eligible if they are of

               1. non-childbearing potential (i.e., physiologically incapable of becoming
                  pregnant); or,

               2. 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

                    -  Hormonal contraception by oral route, implant, injectable, vaginal ring

                    -  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)

                    -  Any other method with published data showing that the lowest expected
                       failure rate is less than 1% per year 4. Able to understand and comply with
                       study procedures required and able and willing to provide written informed
                       consent prior to any study procedures being performed

        Exclusion criteria:

          1. Any current gastric, esophageal or duodenal ulcer

          2. Positive test result for H. pylori at screening 3A. Have had a revascularization
             procedure (i.e., Coronary Artery Bypass Graft, Percutaneous Transluminal Coronary
             Angioplasty, or carotid endarterectomy) less than six months prior to screening

        4. Unstable hypertension as judged by the Investigator 5. Uncontrolled diabetes mellitus as
        judged by the Investigator 6. Unstable cardio- or cerebrovascular disease such that it
        would endanger the subject if they participated in the trial 7. Clinically significant
        valvular disease 8. Congestive heart failure or other cardiovascular symptoms according to
        New York Heart Association (NYHA) Functional Classification III-IV (Appendix 3) 9. History
        of hypersensitivity to omeprazole or to another proton pump inhibitor 10. History of
        allergic reaction or intolerance to aspirin and/or a history of aspirin-induced symptoms of
        asthma, rhinitis, and/or nasal polyps 11. History of serious UGI event, such as bleeding,
        perforation, or obstruction 12. Gastrointestinal disorder or surgery leading to impaired
        drug absorption 13. Presence of chronic or uncontrolled acute medical illness, e.g.
        gastrointestinal disorder (esophageal stricture, severe esophagitis, long-segment Barrett's
        esophagus, signs and symptoms of gastric outlet obstruction), thyroid disorder and/or
        infection that would endanger a subject if they were to participate in the study 14.
        Schizophrenia, uncontrolled bipolar disorder, or severe depression 15. History of
        alcoholism or drug addiction within a year prior to enrollment in the study 16. Severe
        hepatic dysfunction (i.e. cirrhosis or portal hypertension) 17. Blood coagulation disorder,
        including use of systemic anticoagulants such as warfarin or other vitamin K antagonists
        18. Any condition that, in the opinion of the Investigator, may either put the subject at
        risk or influence the results of the study 19. Use of any excluded concomitant medication
        (see Section 9.2) 20. Screening laboratory ALT or AST value > two times the upper limit of
        normal 21A. History of renal insufficiency 22. Other than noted specifically, any screening
        laboratory value that is clinically significant in the Investigator's opinion and would
        endanger a subject if the subject was to participate in the study 23. Use of an
        investigational treatment in the 4 weeks before screening 24. History of malignancy,
        treated or untreated, within the past five years, with the exception of successfully
        treated basal cell or squamous cell carcinoma of the skin 25. Previous participation in
        another PA32540 clinical research study 26. Subjects, who are employees of the research
        facility, immediately related to the Investigator, or are in some way under the supervision
        of the Investigator.