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

Purpose

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

Condition	Intervention	Phase
Healthy	Drug: clopidogrel Drug: Placebo Drug: omeprazole	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-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

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions

Drug Information available for: Omeprazole Omeprazole magnesium Esomeprazole Clopidogrel bisulfate Esomeprazole Sodium Esomeprazole magnesium

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 20µM after 5 days treatment [ Time Frame: Day 5 of each period ] [ Designated as safety issue: No ]
Platelet Reactivity Index - Vasodilatator-stimulated phosphoprotein test (PRI - VASP) after 5 days treatment [ Time Frame: Day 5 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:	March 2009
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group clopidogrel - clopidogrel + omeprazole 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 Pharmaceutical form: tablet Route of administration: oral Other Name: SR25990 Drug: omeprazole Pharmaceutical form: delayed-release capsule Route of administration:oral
Placebo Comparator: Group placebo - placebo + omeprazole 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 Pharmaceutical form: matching tablet Route of administration: oral Drug: omeprazole Pharmaceutical form: delayed-release capsule Route of administration:oral
Experimental: Group clopidogrel + omeprazole - clopidogrel 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 Pharmaceutical form: tablet Route of administration: oral Other Name: SR25990 Drug: omeprazole Pharmaceutical form: delayed-release capsule Route of administration:oral
Placebo Comparator: Group placebo + omeprazole placebo 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 Pharmaceutical form: matching tablet Route of administration: oral Drug: omeprazole Pharmaceutical form: delayed-release capsule Route of administration:oral

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

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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01129388

Locations

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

Sponsors and Collaborators

Sanofi

Bristol-Myers Squibb

Investigators

Study Director:

International Clinical Development Study Director

Sanofi

More Information

Publications:

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. Epub 2010 Sep 15.

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT01129388 History of Changes
Other Study ID Numbers:	INT11166
Study First Received:	May 21, 2010
Last Updated:	December 14, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Omeprazole
Clopidogrel
Ticlopidine
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors

Hematologic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 23, 2013