Clopidogrel Bioequivalence Study in Healthy Subjects

Bioequivalence, AUC, Cmax, Pharmacokinetics Clinical Trial

Official title:

An Open-label, Randomised, Three-way Crossover Study in Healthy Subjects to Assess the Bioequivalence of European Source Generic Clopidogrel Tablets and US and Japanese Source Branded Clopidogrel (Plavix®) Tablets.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02185534
• Other study ID #: D5130C00131
• Status: Completed
• Phase: Phase 1
• First received: July 4, 2014
• Last updated: October 28, 2015
• Start date: August 2014
• Est. completion date: October 2014

Study information

• Verified date: October 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This study will be an open-label, randomised, three-way crossover study in healthy male and female subjects, performed at a single centre. The objective of the study is to assess the bioequivalence between one test formulation (Clopidogrel 75 mg tablet (commercial blister from KRKA) and two reference formulations (Clopidogrel 75 mg tablet [Plavix, sourced in US and Japan]).

Description:

Study to evaluate the bioequivalence of orally administered European source clopidogrel tablets and US and Japanese source clopidogrel tablets.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venepuncture.

• Females must have a negative pregnancy test at screening and on each admission to the clinical unit, must not be lactating and

• if of non child-bearing potential, confirmed at screening by fulfilling one of the following criteria:

• Post-menopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range.

• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

• if of child-bearing potential and are sexually active must use, with their partner, 2 approved methods of highly effective contraception from the time of IMP administration until 3 months after the last dose of IMP.

• Have a body mass index between 18,5 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.

• Be able to understand, read and speak the German language.

Exclusion criteria

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the potential subject at risk because of participation in the study, or influence the results or the potential subject's ability to participate in the study.

• Current smokers or those who have smoked or used nicotine products within the previous 3 months.

• History of haemophilia, von Willebrand's disease, lupus anticoagulant, or other diseases/syndromes that can either alter or increase the propensity for bleeding.

• A personal history of vascular abnormalities including aneurysms; a personal history of severe haemorrhage, haematemesis, melena, haemoptysis, severe epistaxis, severe thrombocytopenia, intracranial haemorrhage; or rectal bleeding within 1 year prior to screening; or history suggestive of peptic ulcer disease; or at the discretion of the Investigator.

• Use of aspirin, ibuprofen, NSAIDS, or any other drug known to increase the propensity for bleeding for 2 weeks before randomisation.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bioequivalence, AUC, Cmax, Pharmacokinetics

Intervention

Drug:
• Clopidogrel
European clopidogrel tablets, 75 mg (test) versus Japanese clopidogrel tablets, 75 mg (reference); European clopidogrel tablets, 75 mg (test) versus US clopidogrel tablets, 75 mg (reference)

Locations

Country	Name	City	State
Germany	Research Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))	Comparison of the pharmacokinetic profile in terms of plasma concentration-time curve from time zero extrapolated to infinity, AUC(0-inf), of clopidogrel sourced in Europe and Japan.	0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose	No
Primary	Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)	Comparison of the pharmacokinetic profile in terms of observed maximum plasma concentration, taken directly from the individual concentration-time curve, Cmax, of clopidogrel sourced in Europe and the US.	0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose	No
Secondary	Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))	Comparison of the pharmacokinetic profile in terms of the area under the plasma concentration-curve from time zero to the time of last quantifiable clopidogrel or SR26334 concentration, AUC(0-last), of clopidogrel sourced in Europe and the US.	0 hours (pre-dose), as well as at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hours post-dose	No