To Compare the Gastroprotective Effects and Pharmacokinetic Profile of PA Versus Enteric-Coated Aspirin

POZEN

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: aspirin

Drug: omeprazole

Study type

Interventional

Funder types

Industry

Identifiers

NCT00442052

PA325-101

Details and patient eligibility

About

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 325 mg enteric coated aspirin utilizing Lanza scores from endoscopy findings in normal healthy volunteers.

Full description

PA 325 is proposed for the reduction in the risk of aspirin-associated gastrointestinal (GI) adverse events in patients requiring daily aspirin. This study is designed as a Proof of Concept study to evaluate the gastroprotective effects, pharmacokinetic profile, and safety of PA 325 in healthy volunteers.

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 325 mg enteric coated aspirin utilizing Lanza scores from endoscopy findings in normal healthy volunteers.

Sex

All

Ages

50 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

A subject will be eligible for inclusion in this study if all of the following criteria apply:
- Subject is a male or non-pregnant female
- Subject is 50-75 years of age
- Subject does not currently smoke
- Physical status within normal limits of age and consistent with observations at screening
- BMI of 20-30 kg/m2
Female subjects are eligible for participation in the study if they are of:
- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant); or,
- Childbearing potential, have a negative pregnancy test (urine) 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
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 NSAIDs and/or subject has 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. gastrointestinal disorder, diabetes, hypertension, thyroid disorder, depression and/or infection that would endanger a subject if they were to participate in the study
Gastrointestinal 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 they 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 screening
Screening laboratory value for ALT, AST >2 times the upper limit of normal
Estimated creatinine clearance < 30 ml/min
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
History of hepatitis B or C, a positive test for hepatitis B surface antigen, hepatitis C antibody, a history of HIV infection, 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