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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: clopidogrel; Drug: Placebo; Drug: omeprazole

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

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

Contacts and Locations

Study Locations

• 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: Yes
• Genders Eligible for Study: All

Description

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.

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 - 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 Names: 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 Names: 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

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 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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General 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. doi: 10.1038/clpt.2010.219. Epub 2010 Sep 15.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 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; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Clopidogrel; Omeprazole
• Other Study ID Numbers: INT11166