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

NCT01129388 | Completed Phase 1

• 1 other identifier: INT11166
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5µM after 5 days treatment

  Day 5 of each period

Secondary Outcomes (4)

• 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

Study Arms (4)

Group clopidogrel - clopidogrel + omeprazole

EXPERIMENTAL

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; Drug: omeprazole

Group placebo - placebo + omeprazole

PLACEBO COMPARATOR

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; Drug: omeprazole

Group clopidogrel + omeprazole - clopidogrel

EXPERIMENTAL

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; Drug: omeprazole

Group placebo + omeprazole placebo

PLACEBO COMPARATOR

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; Drug: omeprazole

Interventions

clopidogrel DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: SR25990

Group clopidogrel + omeprazole - clopidogrel; Group clopidogrel - clopidogrel + omeprazole

Placebo DRUG

Pharmaceutical form: matching tablet Route of administration: oral

Group placebo + omeprazole placebo; Group placebo - placebo + omeprazole

omeprazole DRUG

Pharmaceutical form: delayed-release capsule Route of administration:oral

Group clopidogrel + omeprazole - clopidogrel; Group clopidogrel - clopidogrel + omeprazole; Group placebo + omeprazole placebo; Group placebo - placebo + omeprazole

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Related Publications (1)

• 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.

  PMID: 20844485 RESULT

MeSH Terms

Interventions

Clopidogrel; Omeprazole

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Benzimidazoles

Study Officials

• International Clinical Development Study Director

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: May 24, 2010
• Study Start: March 1, 2009
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: December 15, 2011

Record last verified: 2011-12

Locations

US (1)