An Interaction Study to Evaluate the Effect of Esomeprazole/Acetylsalicylic Acid on the Metabolism and Effect of Clopidogrel

NCT01210339 | Completed Phase 1

• 1 other identifier: D961FC00010
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (4)

• 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

  Pharmacodynamic sampling will be done before treatment period 1.

• 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

  Pharmacodynamic sampling will be done after treatment period 1

• 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

  Pharmacodynamic sampling will be done before treatment period 2.

• 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

  Pharmacodynamic sampling will be done after treatment period 2.

Secondary Outcomes (2)

• 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

  Pharmacokinetic sampling will be done at the end of treatment period 1 and 2 (Day 9).

• The safety and tolerability of clopidogrel alone and in combination with esomeprazole/ acetylsalicylic acid

  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.

Study Arms (2)

1

EXPERIMENTAL

Treatment A (Clopidogrel 9 days), at least 14 days wash-out, Treatment B (Clopidogrel 4 days followed by Clopidogrel + Esomeprazole/ASA 5 days)

Drug: Clopidogrel; Drug: Esomeprazole/ASA

2

EXPERIMENTAL

Treatment B (Clopidogrel 4 days followed by Clopidogrel + Esomeprazole/ASA 5 days), at least 14 days wash-out, Treatment A (Clopidogrel 9 days)

Drug: Clopidogrel; Drug: Esomeprazole/ASA

Interventions

Clopidogrel DRUG

Clopidogrel

1; 2

Esomeprazole/ASA DRUG

20 mg/81 mg once daily for five days (Day 5-9)

Also known as: Axanum

1; 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Uppsala, Sweden

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

Conditions

Cardiovascular Diseases

Interventions

Clopidogrel

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

Study Officials

• Peter Nagy, MD

  AstraZeneca

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 27, 2010
• First Posted: September 28, 2010
• Study Start: November 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 7, 2011

Record last verified: 2011-10

Locations

SE (1)