Study Evaluating Effect of Esomeprazole, Omeprazole or Lansoprazole on the Pharmacodynamics (PD) and Pharmacokinetics (PK) of Clopidogrel - Full Text View

Purpose

The aim of this study is to determine if there is a pharmacological interaction between clopidogrel and different types of proton pump inhibitors (PPIs), and if the extent of this possible interaction would change over time.

Condition	Intervention	Phase
Healthy	Drug: lansoprazole Drug: omeprazole Drug: esomeprazole Drug: clopidogrel	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	An Open-label, Randomized, 4-treatment, 3-period, Crossover Interaction Study, Evaluating the Effect of Esomeprazole 40 mg, Omeprazole 80 mg or Lansoprazole 60 mg on the Pharmacodynamics and the Pharmacokinetics of Clopidogrel in Healthy Volunteers

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions

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

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA). [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA). [ Time Frame: Day 2 ] [ Designated as safety issue: Yes ]
Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA). [ Time Frame: Day 6 ] [ Designated as safety issue: Yes ]
Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA). [ Time Frame: Day 15 ] [ Designated as safety issue: Yes ]
Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the inhibition of platelet aggregation (mIPA). [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Assess the effect of esomeprazole 40 mg, omeprazole 80 mg or lansoprazole 60 mg on the PK profile of clopidogrel active metabolite by assessing the AUC, AUC 0-t and Cmax after the loading dose of clopidogrel (Day 1) and AUC 0-t, ss and Css, max. [ Time Frame: Days 5,14, 29 ] [ Designated as safety issue: Yes ]
Evaluate the safety and tolerability of clopidogrel given concomittantly with esomeprazole, omeprazole or lansoprazole by assessment of adverse events and calculation of change from baseline for clinical laboratory tests, vital signs and pECG. [ Time Frame: Every in-house day ] [ Designated as safety issue: Yes ]

Enrollment:	149
Study Start Date:	May 2010
Study Completion Date:	May 2011
Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 lansoprazole 60 mg + clopidogrel 300 mg/ 75 mg	Drug: lansoprazole 60 mg (2x30-mg capsule), once daily Drug: clopidogrel 300 mg loading dose on Day 1 then 75 mg daily for 28 days
Experimental: 2 omeprazole 80 mg + clopidogrel 300/75 mg	Drug: omeprazole 80 mg (2x40-mg capsule), once daily Drug: clopidogrel 300 mg loading dose on Day 1 then 75 mg daily for 28 days
Experimental: 3 esomeprazole 40 mg + clopidogrel 300/75 mg	Drug: esomeprazole 40 mg (1x40-mg capsule), once daily Drug: clopidogrel 300 mg loading dose on Day 1 then 75 mg daily for 28 days
Experimental: 4 clopidogrel 300/75 mg alone	Drug: clopidogrel 300 mg loading dose on Day 1 then 75 mg daily for 28 days

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy males within the age of 18-45 years and females within the age of 18-55 years with suitable veins for cannulation or repeated vein puncture. Females must be of non-childbearing potential.
Weight of 50-95kg, inclusive, and a BMI between 19-30 kg/m2, inclusive.
No clinically significant abnormal findings as judged by the Investigator on enrollment physical exam.

Exclusion Criteria:

History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in study.
History or presence of gastrointestinal e.g. GI ulcer, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
Any clinically significant illness within 4 weeks of the first administration of investigational product. Any medical/surgical procedure or trauma within 3 months of the treatment period; scheduled surgery, including dental surgery within 2 weeks.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147588

Locations

United States, Kansas
Research Site
Overland Park, Kansas, United States

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator:	Kelli Craven, MD	Quintiles
Study Director:	Ken Price	AstraZeneca
Study Chair:	Mirjana Kujacic	AstraZeneca

More Information

No publications provided

Responsible Party:	MSD, AstraZeneca
ClinicalTrials.gov Identifier:	NCT01147588 History of Changes
Other Study ID Numbers:	D9612C00034
Study First Received:	June 4, 2010
Last Updated:	June 27, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

open label
randomized
4-treatment
3-period
crossover

interaction study
Safety
tolerability
pharmacokinetics
pharmacodynamics

Additional relevant MeSH terms:

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

Anti-Infective Agents
Platelet Aggregation Inhibitors
Hematologic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013