Bioequivalence, AUC, Cmax, PharmacokineticsPhase 1NCT02185534

Clopidogrel Bioequivalence Study in Healthy Subjects

A Phase 1 study testing Clopidogrel in people with Bioequivalence, AUC, Cmax, Pharmacokinetics, run by AstraZeneca at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Bioequivalence, AUC, Cmax, Pharmacokinetics
What is being tested?: Clopidogrel
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 144 participants
Where: 1 siteGermany
Study dates: Aug 2014to Oct 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

Germany1 site

Research Site
Berlin

Other trials in Germany

About this study

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.

Read the detailed description

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

Conditions: Bioequivalence, AUC, Cmax, Pharmacokinetics
Being tested: Clopidogrel
Keywords: Clopidogrel, Zyllt, Plavix, Phase I, Healthy Subjects, Pharmacokinetics, Bioequivalence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ClopidogrelDrug
Also called Zyllt, Plavix
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)

Study groups in NCT02185534
Study group	Role	What they receive
European clopidogrel tablets, 75 mg	Experimental	Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet (Zyllt, KRKA - test) Receives: 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) Receives: 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) Receives: Drug: Clopidogrel

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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))
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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2014Oct 2014

First posted9 Jul 2014 (estimated)
Study startAug 2014
Primary completionOct 2014
Study completionOct 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bioequivalence, AUC, Cmax, PharmacokineticsStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 144 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02185534
Sponsor's protocol ID: D5130C00131
Status last verified: May 2016
First submitted: 4 Jul 2014
Last updated: 22 Jun 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 22 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT02185534
Acronym / sponsor ID: D5130C00131
Conditions: Bioequivalence, AUC, Cmax, Pharmacokinetics
Keywords: Clopidogrel, Zyllt, Plavix, Phase I, Healthy Subjects, Pharmacokinetics, Bioequivalence
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 144 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Aug 2014
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 9 Jul 2014 (estimated)
Results: Posted 30 Nov 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
European clopidogrel tablets, 75 mg	Experimental	Drug: ClopidogrelTreatment A: a single oral dose of clopidogrel 75 mg film-coated tablet (Zyllt, KRKA - test)
Japanese clopidogrel tablets, 75 mg	Active comparator	Drug: ClopidogrelTreatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi-Aventis, reference)
US clopidogrel tablets, 75 mg	Active comparator	Drug: ClopidogrelTreatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

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
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.
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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ClopidogrelAlso: Zyllt, PlavixEuropean 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)	Drug	European clopidogrel tablets, 75 mg, Japanese clopidogrel tablets, 75 mg, US clopidogrel tablets, 75 mg

Primary outcome

Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))
Time frame: 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
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.
Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)
Time frame: 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
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.

1 secondary outcome

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

Results and safety

Results posted to the registry on 30 Nov 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
First European, Then Japanese, Then US Clopidogrel	14	14
First European, Then US, Then Japanese Clopidogrel	14	14
First Japanese, Then European, Then US Clopidogrel	14	14
First Japanese, Then US, Then European Clopidogrel	14	13
First US, Then European, Then Japanese Clopidogrel	14	14
First US, Then Japanese, Then European Clopidogrel	14	14

Primary outcome: Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*h/mL

Measure	European Clopidogrel Tablets, 75 mg n = 41	Japanese Clopidogrel Tablets, 75 mg n = 45	US Clopidogrel Tablets, 75 mg n = 38
Value	1.05 (139.0)	0.992 (117.9)	1.09 (106.9)

European Clopidogrel Tablets, 75 mg vs Japanese Clopidogrel Tablets, 75 mg: Geometric mean ratio: 104.43 (90% CI 92.27 to 118.19)
European Clopidogrel Tablets, 75 mg vs US Clopidogrel Tablets, 75 mg: Geometric mean ratio: 97.19 (90% CI 81.12 to 116.45)

Population analysed: The pharmacokinetic population consisted of 79 subjects, i.e. all subjects in the safety population for whom AUC(0-last) and Cmax could be calculated for clopidogrel for the test treatment (European) and at least one of the reference treatments (Japanese, US). AUC(0-inf) could not be reliably calculated for many of these subjects.

Primary outcome: Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	European Clopidogrel Tablets, 75 mg n = 79	Japanese Clopidogrel Tablets, 75 mg n = 79	US Clopidogrel Tablets, 75 mg n = 79
Value	0.551 (122.6)	0.511 (150.6)	0.521 (122.4)

European Clopidogrel Tablets, 75 mg vs Japanese Clopidogrel Tablets, 75 mg: Geometric mean ratio: 108.06 (90% CI 95.46 to 122.33)
European Clopidogrel Tablets, 75 mg vs US Clopidogrel Tablets, 75 mg: Geometric mean ratio: 105.79 (90% CI 95.22 to 117.53)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From screening until follow-up, i.e. up to 7 weeks after the first dose.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
European Clopidogrel Tablets, 75 mg	0 of 81 (0%)	19 of 81 (23.5%)	Not reported
Japanese Clopidogrel Tablets, 75 mg	0 of 80 (0%)	18 of 80 (22.5%)	Not reported
US Clopidogrel Tablets, 75 mg	0 of 82 (0%)	22 of 82 (26.8%)	Not reported
Total Number of Participants	0 of 83 (0%)	38 of 83 (45.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rainard Fuhr, Dr. med. principal investigator

PAREXEL International GmbH, Berlin

Glenn Carlson, MD study director

AstraZeneca, Wilmington, US

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Clopidogrel in people with Bioequivalence, AUC, Cmax, Pharmacokinetics, run by AstraZeneca at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf)) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02185534.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2016.