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

NCT01147588 | Completed Phase 1

• 1 other identifier: D9612C00034
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

open label; randomized; 4-treatment; 3-period; crossover; interaction study; Safety; tolerability; pharmacokinetics; pharmacodynamics

Outcome Measures

Primary Outcomes (5)

• 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).

  Baseline

• 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).

  Day 2

• 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).

  Day 6

• 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).

  Day 15

• 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).

  Day 30

Secondary Outcomes (2)

• 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.

  Days 5,14, 29

• 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.

  Every in-house day

Study Arms (4)

1

EXPERIMENTAL

lansoprazole 60 mg + clopidogrel 300 mg/ 75 mg

Drug: lansoprazole; Drug: clopidogrel

2

EXPERIMENTAL

omeprazole 80 mg + clopidogrel 300/75 mg

Drug: omeprazole; Drug: clopidogrel

3

EXPERIMENTAL

esomeprazole 40 mg + clopidogrel 300/75 mg

Drug: esomeprazole; Drug: clopidogrel

4

EXPERIMENTAL

clopidogrel 300/75 mg alone

Drug: clopidogrel

Interventions

lansoprazole DRUG

60 mg (2x30-mg capsule), once daily

1

omeprazole DRUG

80 mg (2x40-mg capsule), once daily

2

esomeprazole DRUG

40 mg (1x40-mg capsule), once daily

3

clopidogrel DRUG

300 mg loading dose on Day 1 then 75 mg daily for 28 days

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

Related Publications (1)

• 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.

  PMID: 24677117 DERIVED

MeSH Terms

Interventions

Lansoprazole; Omeprazole; Esomeprazole; Clopidogrel

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kelli Craven, MD

  Quintiles, Inc.

  PRINCIPAL INVESTIGATOR

• Ken Price

  AstraZeneca

  STUDY DIRECTOR

• Mirjana Kujacic

  AstraZeneca

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: June 22, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 28, 2011

Record last verified: 2011-06

Locations

US (1)