Clopidogrel Bioequivalence Study in Healthy Subjects

NCT02185534 | Completed Phase 1 Results

• 1 other identifier: D5130C00131
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief 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 \[Plavix, sourced in US and Japan\]).

Conditions

Bioequivalence, AUC, Cmax, Pharmacokinetics

Keywords

Clopidogrel, Zyllt, Plavix, Phase I, Healthy Subjects, Pharmacokinetics, Bioequivalence

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (1)

• Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))

  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

Study Arms (3)

European clopidogrel tablets, 75 mg

EXPERIMENTAL

Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet (Zyllt, KRKA - test)

Drug: Clopidogrel

Japanese clopidogrel tablets, 75 mg

ACTIVE COMPARATOR

Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi-Aventis, reference)

Drug: Clopidogrel

US clopidogrel tablets, 75 mg

ACTIVE COMPARATOR

Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

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)

Also known as: Zyllt, Plavix

European clopidogrel tablets, 75 mg; Japanese clopidogrel tablets, 75 mg; US clopidogrel tablets, 75 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Berlin, Germany

Location

MeSH Terms

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

Results Point of Contact

• Title: Brilinta Global Clinical Leader
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+46 31 776 1000

Study Officials

• Rainard Fuhr, Dr. med.

  PAREXEL International GmbH, Berlin

  PRINCIPAL INVESTIGATOR

• Glenn Carlson, MD

  AstraZeneca, Wilmington, US

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: July 4, 2014
• First Posted: July 9, 2014
• Study Start: August 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: June 22, 2016
• Results First Posted: November 30, 2015

Record last verified: 2016-05

Locations

DE (1)