Study to Evaluate the Long-Term Safety of PA32540 in Subjects Who Are at Risk for Developing Aspirin-Associated Gastric Ulcers

Study Overview
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Brief Summary
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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.

Detailed Description
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PA32540 is proposed for the secondary prevention of cardio- and cerebrovascular events in patients at risk for developing aspirin-associated gastric ulcers. This study is designed to provide long-term safety data for PA32540 in order to gain regulatory approval to make PA32540 available for clinical use in this subject population.

Official Title
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A 12-Month, Phase 3, Open-Label, Multi-Center Study to Evaluate the Long-Term Safety of PA32540 in Subjects Who Are at Risk for Developing Aspirin-Associated Gastric Ulcers

Conditions
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Aspirin-Associated Gastric Ulcers

Intervention / Treatment
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* Drug: PA32540


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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. 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 A. If female, subjects are eligible if they are of non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or, 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: Any current gastric, esophageal or duodenal ulcer 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.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PA32540 tablet<br>325 mg enteric coated (EC) ASA and 40 mg omeprazole to be taken by mouth once daily | Drug: PA32540<br>* PA32540 tablets contain 325 mg enteric coated (EC) aspirin and 40 mg immediate-release omeprazole to be taken by mouth once daily<br>* Other names: YOSPRALA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Monitored for Long-term Safety of PA32540 | Incidence of adverse events and monitoring vital signs and clinical laboratory values. All AEs were coded into preferred terms according to MedDRA (Medical Dictionary for Regulatory Activities) and classified by system organ class (SOC). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Most Frequent Treatment Emergent Adverse Events Leading to Study Drug Discontinuation | Most Frequent (≥ 1%) Treatment Emergent Adverse Events by System Organ Class leading to Discontinuation | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subjects Who are at Risk for Developing Aspirin-ASA, Subject must have a pre-existing condition for which aspirin is already indicated, Gastric Ulcers