Clinical trial NCT01129388: Interaction Study of Clopidogrel 300/75 mg Given Alone or With Omeprazole 80 mg 12 Hours Apart in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2010-05-24
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5µM after 5 days treatment
timeFrame: Day 5 of each period
Secondary outcomes:
measure: Maximum platelet aggregation intensity (MAI) induced by ADP 20µM after 5 days treatment
timeFrame: Day 5 of each period
measure: Platelet Reactivity Index - Vasodilatator-stimulated phosphoprotein test (PRI - VASP) after 5 days treatment
timeFrame: Day 5 of each period
measure: Clopidogrel pharmacokinetic parameters (maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC0-24)) after 5 days treatment
timeFrame: Up to 24 hours postdose on Day 5 for each period
measure: Clopidogrel active metabolite pharmacokinetic parameters (Cmax and AUC0-24) after 5 days treatment
timeFrame: Up to 24 hours postdose on Day 5 for each period
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
Study officials:
affiliation: Sanofi
name: International Clinical Development Study Director
role: STUDY_DIRECTOR
References:
citation: Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O, Bergougnan L, Perrin L, LaCreta FP, Hurbin F, Dubar M. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther. 2011 Jan;89(1):65-74. doi: 10.1038/clpt.2010.219. Epub 2010 Sep 15.