Interaction Study of Clopidogrel 300/75 mg Given Alone or With Omeprazole 80 mg 12 Hours Apart in Healthy Subjects

Study Overview
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Brief Summary
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Primary objective: Assess the effects of clopidogrel (300 mg loading dose followed by 4 days 75 mg/day) on Adenosine diphosphate (ADP)-induced platelet aggregation when given either alone in the morning, or in association with omeprazole 80 mg/day in the evening at a 12-hours interval in healthy male and female subjects Secondary Objectives: Compare the pharmacokinetic profiles of clopidogrel and its active metabolite when clopidogrel is given either alone alone in the morning, or in association with omeprazole in the evening at a 12-hours interval

Detailed Description
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The total study duration per subjects is 8-9 weeks broken down as follows: Screening: 2 to 21 days before the first dosing Period clopidogrel/placebo: 7 days including 5 days treatment Period clopidogrel/placebo + omeprazole: 12 days including 10 days treatment Washout between periods: at least 14 days period after last dosing respect to clopidogrel treatment End of study: at 7 to 10 days after the last dosing

Official Title
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A Randomized, Placebo-controlled, Two-period, Two-treatment, Two Sequence, Cross-over Pharmacodynamic and Pharmacokinetic Interaction Study After 5-days Repeated Oral Doses of Clopidogrel (300 mg Loading Dose Followed by 75 mg/Day) Alone or Given With Omeprazole 80 mg/Day (12 Hours Apart on the Same Days) in Healthy Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: clopidogrel
* Drug: Placebo
* Drug: omeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subject, as determined by medical history, physical examination including vital signs and clinical laboratory tests. with a body weight between 50 kg and 95 kg if male, between 40 kg and 85 kg if female, and with 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 Unability to abstain from intake of any drug affecting hemostasis throughout the whole study duration Any contraindication to clopidogrel and/or omeprazole 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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All

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 - clopidogrel + omeprazole<br>Period 1: Day 1: clopidogrel 300 mg loading dose in the morning under fasted conditions Day 2 to Day 5: clopidogrel 75 mg in the morning under fasted conditions, once daily Period 2: Day -5 to Day -1: omeprazole 80 mg in the evening 2 hours after dinner, once daily Day 1: clopidogrel 300 mg loading dose in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner Day 2 to Day 5: clopidogrel 75 mg in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner, once daily | Drug: clopidogrel<br>* Pharmaceutical form: tablet Route of administration: oral<br>* Other names: SR25990;Drug: omeprazole<br>* Pharmaceutical form: delayed-release capsule Route of administration:oral<br>|
| Placebo Comparator: Group placebo - placebo + omeprazole<br>Period 1: Day 1: placebo loading dose in the morning under fasted conditions Day 2 to Day 5: placebo in the morning under fasted conditions, once daily Period 2: Day -5 to Day -1: omeprazole 80 mg in the evening 2 hours after dinner, once daily Day 1: placebo loading dose in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner Day 2 to Day 5: placebo in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner, once daily | Drug: Placebo<br>* Pharmaceutical form: matching tablet Route of administration: oral<br>Drug: omeprazole<br>* Pharmaceutical form: delayed-release capsule Route of administration:oral<br>|
| Experimental: Group clopidogrel + omeprazole - clopidogrel<br>Period 1: Day -5 to Day -1: omeprazole 80 mgin the evening 2 hours after dinner, once daily Day 1: clopidogrel 300 mg loading dose in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner Day 2 to Day 5: clopidogrel 75 mg in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner, once daily Period 2: Day 1: clopidogrel 300 mg loading dose in the morning under fasted conditions Day 2 to Day 5: clopidogrel 75 mg in the morning under fasted conditions, once daily | Drug: clopidogrel<br>* Pharmaceutical form: tablet Route of administration: oral<br>* Other names: SR25990;Drug: omeprazole<br>* Pharmaceutical form: delayed-release capsule Route of administration:oral<br>|
| Placebo Comparator: Group placebo + omeprazole placebo<br>Period 1: Day -5 to Day -1: omeprazole 80 mg, once daily in the evening 2 hours after dinner Day 1: placebo loading dose in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner Day 2 to Day 5: placebo in the morning under fasted conditions + omeprazole 80 mg in the evening 2 hours after dinner, once daily Period 2: Day 1: placebo loading dose in the morning under fasted conditions Day 2 to Day 5: placebo in the morning under fasted conditions, once daily | Drug: Placebo<br>* Pharmaceutical form: matching tablet Route of administration: oral<br>Drug: omeprazole<br>* Pharmaceutical form: delayed-release capsule 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 20µM after 5 days treatment |  | Day 5 of each period | 
| Platelet Reactivity Index - Vasodilatator-stimulated phosphoprotein test (PRI - VASP) after 5 days treatment |  | Day 5 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 |