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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: clopidogrel; Drug: Matching placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group clopidogrel fed - fasting; 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; Pharmaceutical form: tablet Route of administration: oral
Placebo Comparator: Group placebo fed - fasting; 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; Pharmaceutical form: tablet Route of administration: oral
Experimental: Group clopidogrel fasting - fed; 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; Pharmaceutical form: tablet Route of administration: oral
Placebo Comparator: group placebo fasting -fed; 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; Pharmaceutical form: tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Hurbin F, Boulenc X, Daskalakis N, Farenc C, Taylor T, Bonneau D, Lacreta F, Cheng S, Sultan E. Clopidogrel pharmacodynamics and pharmacokinetics in the fed and fasted state: a randomized crossover study of healthy men. J Clin Pharmacol. 2012 Oct;52(10):1506-15. doi: 10.1177/0091270011419852. Epub 2011 Nov 29.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 21, 2010
• First Posted (Estimate): May 24, 2010

Study Record Updates

• Last Update Posted (Estimate): December 15, 2011
• Last Update Submitted That Met QC Criteria: December 14, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: ALI11209

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No