A Study to Evaluate Platlet Aggregation of Clopidogrel, EC Aspirin 81 mg, EC Omeprazole 40 mg Compare to PA32540

A Randomized, Open-Label, Cross-Over, Study to Evaluate the Inhibitory Effect of Clopidogrel, EC Aspirin 81 mg and EC Omeprazole 40 mg All Dosed Concomitantly and PA32540 and Clopidogrel Dosed Separately on Platelet Aggregation in Healthy Volunteers

This study is designed to provide data on platelet aggregation of PA32540 plus clopidogrel dosed separately compared to EC aspirin 81 mg plus EC omeprazole 40 mg plus clopidogrel dosed concomitantly.

Study Overview

• Status: Completed
• Conditions: Platelet Aggregation
• Intervention / Treatment: Drug: Plavix® and PA32540; Drug: EC aspirin (Bayer®) ,EC omeprazole (Prilosec®) , Clopidogrel (Plavix®)

Detailed Description

PA32540 is proposed for the secondary prevention of cardio- and cerebrovascular events in patients at risk for developing aspirin-associated gastric ulcers.

Aspirin 81 mg taken concomitantly with clopidogrel 75 mg as maintenance doses is standard of care in some patients with cardiovascular disease. The combination of aspirin and clopidogrel, however, significantly increases the risk for bleeding events. To mitigate upper gastrointestinal bleeding events, these patients would require the use of a proton pump inhibitor. For that reason, the reference arm in this study uses Prilosec® 40 mg as a comparator - the same proton pump inhibitor at the same dose level.

The primary objective is to evaluate adenosine diphosphate (ADP)-induced platelet aggregation following administration of clopidogrel, EC aspirin 81 mg and EC omeprazole 40 mg, all dosed concomitantly, and PA32540 and clopidogrel dosed separately

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Center for Thrombosis Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-lactating, non-pregnant female subjects who are 40 years or older at the time of initial dosing

  --Physical status within normal limits for age and consistent with observations at Screening

• 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:

• History of hypersensitivity, allergy or intolerance to omeprazole or other proton-pump inhibitors (PPIs)
• History of hypersensitivity, allergy or intolerance to aspirin or any NSAID and/or a history of NSAID-induced symptoms of asthma, rhinitis, and/or nasal polyps
• History of hypersensitivity or intolerance to clopidogrel
• History of hepatitis B or C, a positive test for hepatitis B surface antigen, hepatitis C antibody, a history of human immunodeficiency virus (HIV) infection or demonstration of HIV antibodies
• History of malignancy, treated or untreated, within the past five years, with the exception of successfully treated basal cell or squamous cell carcinoma of -Evidence of uncontrolled, or unstable cardio- or cerebrovascular disorder, which in the Investigator's opinion, would endanger a subject if he/she were to participate in the study
• Presence of an uncontrolled acute, or a chronic medical illness, e.g., GI disorder, diabetes, hypertension, thyroid disorder, bleeding disorder, infection, which in the Investigator's opinion would endanger a subject if he/she were to participate in the study or interfere with the objective of this study
• Schizophrenia or bipolar disorder
• GI disorder or surgery leading to impaired drug absorption
• < 70% platelet aggregation at Screening
• Donation of blood or plasma within 4 weeks of the study
• PPI use or any enzyme inducing/inhibiting agents within 4 weeks prior to dosing
• Taking any antiplatelet drug within 2 weeks of the screening visit or during the study, or more than two 325 mg doses of aspirin or more than 2 doses of any other NSAIDs within 14 days prior to the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clopidogrel (Plavix®) and PA32540; PA32540 and Clopidogrel (Plavix®) tablet, 10 hours post PA32540	Drug: Plavix® and PA32540; one Plavix® 300 mg loading dose in the PM of Day 1 one Plavix® 75 mg maintenance dose in the PM of Days 2-7 PA32540(delayed release aspirin 325 mg plus immediate release omeprazole 40 mg)
Active Comparator: EC aspirin, EC omeprazole, Clopidogrel	Drug: EC aspirin (Bayer®) ,EC omeprazole (Prilosec®) , Clopidogrel (Plavix®); One EC aspirin (Bayer®) 81 mg tablet plus one EC omeprazole (Prilosec®) 40 mg capsule plus one Clopidogrel (Plavix®) tablet of 300 mg (loading dose) all One EC aspirin (Bayer®) 81 mg tablet plus one EC omeprazole (Prilosec®) 40 mg capsule plus one Clopidogrel (Plavix®) tablet of 75 mg (maintenance dose) all taken concomitantly in the AM of Days 2-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate adenosine diphosphate (ADP)-induced platelet aggregation	To evaluate adenosine diphosphate (ADP)-induced platelet aggregation following administration of clopidogrel, EC aspirin 81 mg and EC omeprazole 40 mg, all dosed concomitantly, and PA32540 and clopidogrel dosed separately. The endpoint measure is IPA (Individual Platelet Aggregation)at day 7 and PA0 is the platelet aggregation at baseline. The IPA will be analyzed using analyses of variance (ANOVA).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate arachidonic acid (AA)-induced platelet aggregation	To evaluate arachidonic acid (AA)-induced platelet aggregation following administration of clopidogrel, EC aspirin 81 mg and EC omeprazole 40 mg, all dosed concomitantly, and PA32540 and clopidogrel dosed separately. The secondary endpoint is the IPA (Individual Platelet Aggregation) and will be analyzed using the same methodology as the primary endpoint.	7 days

Collaborators and Investigators

• Sponsor: POZEN
• Investigators: Study Director: Lisa Zimmerman, Pozen

Publications and helpful links

General Publications

• Gurbel PA, Bliden KP, Fort JG, Jeong YH, Shuldiner A, Chai S, Gesheff T, Antonino M, Gesheff M, Zhang Y, Tantry US. Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel. Am Heart J. 2013 Feb;165(2):176-82. doi: 10.1016/j.ahj.2012.07.032. Epub 2012 Dec 4.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: March 13, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (Estimate): March 19, 2012

Study Record Updates

• Last Update Posted (Estimate): March 19, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: To evaluate adenosine diphosphate (ADP)-induced platelet aggregation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Aspirin; Clopidogrel; Omeprazole
• Other Study ID Numbers: PA32540-111