Clinical trial NCT01210339: An Interaction Study to Evaluate the Effect of Esomeprazole/Acetylsalicylic Acid on the Metabolism and Effect of Clopidogrel
Official title: An Open-label, Randomized, Single-center, 2-way Cross-over Interaction Study, Evaluating the Effect of Esomeprazole 20 mg/Acetylsalicylic Acid 81 mg on the Pharmacodynamics and the Pharmacokinetics of Clopidogrel on Days 1 and 9 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: phase 1
cross-over
drug-drug Interaction
esomeprazole
acetylsalicylic acid
clopidogrel
healthy volunteers
cardiovascular disease
patients with acid associated gastrointestinal symptoms
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-09-28
Enrollment: 58
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 primary purpose of this study is to assess whether esomeprazole 20 mg/Acetyl Salicylic Acid (ASA) 81 mg affect the metabolism of clopidogrel.


Eligibility criteria: Inclusion Criteria:

* Male (aged between 18 and 45 years inclusive) or female (aged between 18 and 55 years inclusive) healthy volunteers
* Female healthy volunteers must be of non-childbearing potential or be of childbearing potential, be non-lactating and have a negative pregnancy test during the pre-entry visit and be using 1 clinically accepted method of contraception
* Have a body mass index between 19 and 30 kg/m2 inclusive
* No clinically significant abnormal findings at the physical examination as judged by the investigator

Exclusion Criteria:

* Any clinically significant abnormalities in laboratory screening results as judged by investigator
* Platelet count \<150 x 10\^9/L on Day -1 or any other conditions that would increase the risk of bleeding
* Previous bone marrow transplant
* Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG

Primary outcomes:
measure: The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline
timeFrame: Pharmacodynamic sampling will be done before treatment period 1.
measure: The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline
timeFrame: Pharmacodynamic sampling will be done after treatment period 1
measure: The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline
timeFrame: Pharmacodynamic sampling will be done before treatment period 2.
measure: The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacodynamics of clopidogrel by assessing maximal inhibition of platelet aggregation after 9 days of clopidogrel treatment relative to baseline
timeFrame: Pharmacodynamic sampling will be done after treatment period 2.
Secondary outcomes:
measure: The effect of esomeprazole 20 mg/ acetylsalicylic acid 81 mg on the pharmacokinetics of the active metabolite of clopidogrel by assessing Area Under Curve (AUC) and Cmax.after 9 days of clopidogrel treatment
timeFrame: Pharmacokinetic sampling will be done at the end of treatment period 1 and 2 (Day 9).
measure: The safety and tolerability of clopidogrel alone and in combination with esomeprazole/ acetylsalicylic acid
timeFrame: Safety will be monitored continuously. Adverse events will be collected from the first administration of Investigational Product (IP) throughout the study until the follow-up visit (on average) 7-10 days after last dose.
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Peter Nagy, MD
role: STUDY_DIRECTOR
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.