Food Effect Study on Pharmacodynamic and Bioavailability of Clopidogrel 300/75 mg in Healthy Subjects

Study Overview
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Brief Summary
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Primary objective: Investigate the potential food effect on Adenosine diphosphate(ADP)-induced platelet aggregation after 5-day repeated doses of clopidogrel (300 mg loading dose followed by 4 days 75 mg/day) in healthy subjects Secondary objectives are to investigate the potential food effect on: ADP-induced platelet aggregation after 300 mg loading dose of clopidogrel Pharmacokinetic profiles of clopidogrel and its active metabolite after 5-day repeated doses of clopidogrel

Detailed Description
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The total duration per subject is 8-9 weeks broken down as follows: Screening: 2 to 21 days before the first dosing Fed period: 7 days including 5 treatment days Washout: at least 14 days after last dosing Fasted period: 7 days including 5 treatment days End of study: 7 to 10 days after the last dosing

Official Title
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A Randomized, Placebo-controlled, Two-sequence, Two-period Crossover Study, to Investigate a Potential Food Effect on the Pharmacodynamic and Bioavailability of Repeated Oral Doses of Clopidogrel (300 mg Loading Dose Followed by 75 mg/Day) in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: clopidogrel
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects: as determined by medical history, physical examination including vital signs and clinical laboratory tests with a body weight between 50kg and 95 kg and a Body Mass Index (BMI) between 18 and 30 kg/m2 Exclusion Criteria: Evidence of inherited disorder of coagulation/hemostasis functions Smoking more than 5 cigarettes or equivalent per day Abnormal hemostasis screen Any contraindication to clopidogrel Unability to abstain from intake of any drug affecting haemostasis throughout the whole study duration The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group clopidogrel fed - fasting<br>Period 1: Day 1: clopidogrel 300 mg loading dose with high fat breakfast Day 2 to Day 5: clopidogrel 75 mg/day with standard breakfast, once daily Period 2: Day 1: clopidogrel 300 mg loading dose under fasted conditions Day 2 to Day 5: clopidogrel 75 mg/day under fasted conditions, once daily | Drug: clopidogrel<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Placebo Comparator: Group placebo fed - fasting<br>Period 1: Day 1: placebo loading dose with high fat breakfast Day 2 to Day 5: placebo with standard breakfast, once daily Period 2: Day 1: placebo loading dose under fasted conditions Day 2 to Day 5: placebo under fasted conditions, once daily | Drug: Matching placebo<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Experimental: Group clopidogrel fasting - fed<br>Period 1: Day 1: clopidogrel 300 mg loading dose under fasted conditions Day 2 to Day 5: clopidogrel 75 mg/day under fasted conditions, once daily Period 2: Day 1: clopidogrel 300 mg loading dose with high fat breakfast Day 2 to Day 5: clopidogrel 75 mg/day with standard breakfast, once daily | Drug: clopidogrel<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Placebo Comparator: group placebo fasting -fed<br>Period 1: Day 1: placebo loading dose under fasted conditions Day 2 to Day 5: placebo in fasted conditions, once daily Period 2: Day 1: placebo loading dose with high fat breakfast Day 2 to Day 5: placebo with standard breakfast, once daily | Drug: Matching placebo<br>* Pharmaceutical form: tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5µM after 5 days treatment |  | Day 5 of each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum platelet aggregation intensity (MAI) induced by ADP 5µM after loading dose and high fat breakfast |  | 6 hours and 24 hours after first dosing of each period | 
| Clopidogrel pharmacokinetic parameters (maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC0-24)) after 5 days treatment |  | up to 24 hours postdose on Day 5 for each period | 
| Clopidogrel active metabolite pharmacokinetic parameters (Cmax and AUC0-24) after 5 days treatment |  | up to 24 hours postdose on Day 5 for each period |