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

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: clopidogrel Drug: Matching placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	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

Resource links provided by NLM:

Drug Information available for: Clopidogrel bisulfate

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5µM after 5 days treatment [ Time Frame: Day 5 of each period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Maximum platelet aggregation intensity (MAI) induced by ADP 5µM after loading dose and high fat breakfast [ Time Frame: 6 hours and 24 hours after first dosing of each period ] [ Designated as safety issue: No ]
Clopidogrel pharmacokinetic parameters (maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC0-24)) after 5 days treatment [ Time Frame: up to 24 hours postdose on Day 5 for each period ] [ Designated as safety issue: No ]
Clopidogrel active metabolite pharmacokinetic parameters (Cmax and AUC0-24) after 5 days treatment [ Time Frame: up to 24 hours postdose on Day 5 for each period ] [ Designated as safety issue: No ]

Enrollment:	72
Study Start Date:	April 2009
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01129271

Locations

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

Sponsors and Collaborators

Sanofi

Bristol-Myers Squibb

Investigators

Study Director:

International Clinical Development Study Director

Sanofi

More Information

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. 2011 Nov 29; [Epub ahead of print]

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT01129271 History of Changes
Other Study ID Numbers:	ALI11209
Study First Received:	May 21, 2010
Last Updated:	December 14, 2011
Health Authority:	United States: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:

Clopidogrel
Ticlopidine
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists

Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 22, 2013