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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01129388
First received: May 21, 2010
Last updated: December 14, 2011
Last verified: December 2011
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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:
Clopidogrel
Omeprazole
Ticlopidine
Anti-Ulcer Agents
Cardiovascular Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Gastrointestinal Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Proton Pump Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014