A Parallel Group Study to Compare the Gastroprotective Effects of PA 325 Versus 81 mg Enteric Coated Aspirin

Primary: To compare the gastroprotective effects of a once-daily dose of PA 325 combination tablet combining 325 mg pH sensitive aspirin and 20 mg immediate release omeprazole versus a once-daily dose of 81 mg enteric coated (EC) aspirin utilizing Lanza scores from endoscopy findings in normal healthy volunteers.

Secondary: To evaluate the safety and gastrointestinal tolerability, including ulcerogenic potential, and the effect on gastric pH of PA 325.

Inclusion criteria

• Subject is a male or a female who is not pregnant or is not lactating. A female is eligible to enter and participate in this study if she is of:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,
• Childbearing potential has a negative pregnancy test at screening, and at least one of the following applies or is agreed to by the subject:

• Complete abstinence from intercourse for at least 14 days prior to first dose of study medication, throughout the study and for 30 days after completion of the study
• 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
• Subject is > 50 years of age inclusive at the time of dosing
• Subject does not currently smoke and has not smoked for at least 3 months
• The subject's physical status is within normal limits of age and consistent with observations at screening
• The subject's Body Mass Index (BMI) is between 20-30 kg/m2
• 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

• History of hypersensitivity to omeprazole or to another proton-pump inhibitor
• History of allergic reaction or intolerance to aspirin or any NSAID and/or a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps
• Participation in any study of an investigational treatment in the 4 weeks before Day 1 dosing
• Presence of uncontrolled acute or chronic medical illness, e.g. GI disorder, hypertension, diabetes, thyroid disorder, depression and/or infection that would endanger a subject if they were to participate in the study
• GI disorder or surgery leading to impaired drug absorption
• Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the investigator's opinion, would endanger a subject if he or she were to participate in the study
• Schizophrenia or bipolar disorder
• Use of any concomitant medication not approved by the study physician during the washout period and during the study conduct
• Serious blood coagulation disorder, including use of systemic anticoagulants
• Subjects who donated 50 to 499 mL of blood within 30 days and more than 499 mL within 56 days prior to dosing
• Subjects who, through completion of the study, would have donated in excess of: 500 mL of blood in 14 days; 1,500 mL of blood in 180 days; 2,500 mL of blood in 1 year
• Baseline endoscopy showing any gastric or duodenal mucosal abnormality (hemorrhages, ulcers or erosions)
• Gastric pH > 3 at Day - 1 endoscopy
• Screening laboratory alanine transaminase (ALT) or aspartate transaminase (AST) value > 2 times the upper limit of normal
• Estimated creatinine clearance < 30 ml/min at screening
• Other than noted specifically, any screening laboratory value that is clinically significant in the investigator's opinion and would endanger a subject if he or she were to participate in the study
• History of hepatitis B or C, a positive test for hepatitis B surface antigen, hepatitis C antibody, a history of HIV infections, or demonstration of HIV antibodies
• 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
• Subjects who have previously been a screen failure in this study
• Subject has excessive alcohol use (>2 units per day on average; for example 2 bottles of beer, two glasses of wine, 2 ounces of liquor/spirits), or recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence
• Subject has ingested grapefruit or grapefruit juice within 10 days of dosing or will ingest grapefruit or grapefruit juice during the duration of the study
• Positive illicit drug screen