Clinical trial NCT01147588: Study Evaluating Effect of Esomeprazole, Omeprazole or Lansoprazole on the Pharmacodynamics (PD) and Pharmacokinetics (PK) of Clopidogrel
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: open label
randomized
4-treatment
3-period
crossover
interaction study
Safety
tolerability
pharmacokinetics
pharmacodynamics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-06-22
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: 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).
timeFrame: Baseline
measure: 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).
timeFrame: Day 2
measure: 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).
timeFrame: Day 6
measure: 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).
timeFrame: Day 15
measure: 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).
timeFrame: Day 30
Secondary outcomes:
measure: 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.
timeFrame: Days 5,14, 29
measure: 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.
timeFrame: Every in-house day
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: Quintiles, Inc.
name: Kelli Craven, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Ken Price
role: STUDY_DIRECTOR
affiliation: AstraZeneca
name: Mirjana Kujacic
role: STUDY_CHAIR
References:
citation: Andersson T, Nagy P, Niazi M, Nylander S, Galbraith H, Ranjan S, Wallentin L. Effect of esomeprazole with/without acetylsalicylic acid, omeprazole and lansoprazole on pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. Am J Cardiovasc Drugs. 2014 Jun;14(3):217-27. doi: 10.1007/s40256-014-0073-4.