Trial Outcomes & Findings for Clopidogrel Bioequivalence Study in Healthy Subjects (NCT NCT02185534)

Last Updated: 2016-06-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

144 participants

Primary outcome timeframe

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 posted on

2016-06-22

Participant Flow

Participants recruited at PAREXEL Early Phase Clinical Unit Berlin, Germany between August 2014 and September 2014.

84 participants recruited; 144 screened, 60 excluded (59 did not meet inclusion criteria and 1 refused participation)

Participant milestones

Participant milestones
Measure	First European, Then Japanese, Then US Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA \- test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3	First European, Then US, Then Japanese Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3	First Japanese, Then European, Then US Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi-Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3	First Japanese, Then US, Then European Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3	First US, Then European, Then Japanese Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1, a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3	First US, Then Japanese, Then European Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3
First Period STARTED	14	14	14	14	14	14
First Period COMPLETED	14	14	14	13	14	14
First Period NOT COMPLETED	0	0	0	1	0	0
First Washout Period STARTED	14	14	14	13	14	14
First Washout Period COMPLETED	13	14	14	13	13	13
First Washout Period NOT COMPLETED	1	0	0	0	1	1
Second Period STARTED	13	14	14	13	13	13
Second Period COMPLETED	13	14	14	13	13	13
Second Period NOT COMPLETED	0	0	0	0	0	0
Second Washout Period STARTED	13	14	14	13	13	13
Second Washout Period COMPLETED	13	14	14	13	13	13
Second Washout Period NOT COMPLETED	0	0	0	0	0	0
Third Period STARTED	13	14	14	13	13	13
Third Period COMPLETED	13	14	14	13	13	13
Third Period NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	First European, Then Japanese, Then US Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA \- test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3	First Japanese, Then US, Then European Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3	First US, Then European, Then Japanese Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1, a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3	First US, Then Japanese, Then European Clopidogrel A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3
First Period Withdrawal by Subject	0	1	0	0
First Washout Period Withdrawal by Subject	1	0	1	0
First Washout Period Protocol Violation	0	0	0	1

Baseline Characteristics

Clopidogrel Bioequivalence Study in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	First European, Then Japanese, Then US Clopidogrel n=14 Participants A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA \- test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3	First European, Then US, Then Japanese Clopidogrel n=14 Participants A single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3	First Japanese, Then European, Then US Clopidogrel n=14 Participants A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi-Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 3	First Japanese, Then US, Then European Clopidogrel n=14 Participants A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi-Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3	First US, Then European, Then Japanese Clopidogrel n=14 Participants A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1, a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 3	First US, Then Japanese, Then European Clopidogrel n=14 Participants A single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Sanofi- Aventis, reference) in Period 1; a single oral dose of clopidogrel 75 mg filmcoated tablet (Plavix®, Brystol-Myer Squibb, Sanofi- Aventis, reference) in Period 2; a single oral dose of clopidogrel 75 mg filmcoated tablet (Zyllt, KRKA - test) in Period 3	Total n=84 Participants Total of all reporting groups
Age, Continuous	33 years STANDARD_DEVIATION 9 • n=5 Participants	37 years STANDARD_DEVIATION 11 • n=7 Participants	36 years STANDARD_DEVIATION 10 • n=5 Participants	35 years STANDARD_DEVIATION 8 • n=4 Participants	34 years STANDARD_DEVIATION 9 • n=21 Participants	36 years STANDARD_DEVIATION 11 • n=10 Participants	35 years STANDARD_DEVIATION 9 • n=115 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	4 Participants n=21 Participants	4 Participants n=10 Participants	37 Participants n=115 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	7 Participants n=4 Participants	10 Participants n=21 Participants	10 Participants n=10 Participants	47 Participants n=115 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	0 participants n=21 Participants	0 participants n=10 Participants	1 participants n=115 Participants
Race/Ethnicity, Customized White	13 participants n=5 Participants	14 participants n=7 Participants	13 participants n=5 Participants	14 participants n=4 Participants	12 participants n=21 Participants	13 participants n=10 Participants	79 participants n=115 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants	1 participants n=10 Participants	4 participants n=115 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants	1 participants n=10 Participants	3 participants n=115 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	14 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	14 participants n=4 Participants	12 participants n=21 Participants	13 participants n=10 Participants	81 participants n=115 Participants
BMI (Body Mass Index)	23.7 kg/m^2 STANDARD_DEVIATION 3.1 • n=5 Participants	24.7 kg/m^2 STANDARD_DEVIATION 3.5 • n=7 Participants	23.4 kg/m^2 STANDARD_DEVIATION 2.9 • n=5 Participants	24.1 kg/m^2 STANDARD_DEVIATION 2.7 • n=4 Participants	23.0 kg/m^2 STANDARD_DEVIATION 3.1 • n=21 Participants	23.9 kg/m^2 STANDARD_DEVIATION 3.1 • n=10 Participants	23.8 kg/m^2 STANDARD_DEVIATION 3.0 • n=115 Participants

PRIMARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Outcome measures
Measure	European Clopidogrel Tablets, 75 mg n=41 Participants Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)	Japanese Clopidogrel Tablets, 75 mg n=45 Participants Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)	US Clopidogrel Tablets, 75 mg n=38 Participants Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)
Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero Extrapolated to Infinity (AUC(0-inf))	1.05 ng*h/mL Geometric Coefficient of Variation 139.0	0.992 ng*h/mL Geometric Coefficient of Variation 117.9	1.09 ng*h/mL Geometric Coefficient of Variation 106.9

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	European Clopidogrel Tablets, 75 mg n=79 Participants Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)	Japanese Clopidogrel Tablets, 75 mg n=79 Participants Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)	US Clopidogrel Tablets, 75 mg n=79 Participants Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)
Pharmacokinetics of Clopidogrel by Assessment of Observed Maximum Plasma Concentration (Cmax)	0.551 ng/mL Geometric Coefficient of Variation 122.6	0.511 ng/mL Geometric Coefficient of Variation 150.6	0.521 ng/mL Geometric Coefficient of Variation 122.4

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	European Clopidogrel Tablets, 75 mg n=79 Participants Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)	Japanese Clopidogrel Tablets, 75 mg n=79 Participants Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)	US Clopidogrel Tablets, 75 mg n=79 Participants Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)
Pharmacokinetics of Clopidogrel by Assessment of Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC(0-last))	0.705 h*ng/mL Geometric Coefficient of Variation 114.8	0.751 h*ng/mL Geometric Coefficient of Variation 116.5	0.767 h*ng/mL Geometric Coefficient of Variation 107.1

Adverse Events

European Clopidogrel Tablets, 75 mg

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Japanese Clopidogrel Tablets, 75 mg

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

US Clopidogrel Tablets, 75 mg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Total Number of Participants

Serious events: 0 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Brilinta Global Clinical Leader

AstraZeneca

Phone: +46 31 776 1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and AstraZeneca.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	European Clopidogrel Tablets, 75 mg n=81 participants at risk Treatment A: a single oral dose of clopidogrel 75 mg film-coated tablet Eu(Zyllt, KRKA - test)	Japanese Clopidogrel Tablets, 75 mg n=80 participants at risk Treatment B: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Brystol-Myer Squibb,Sanofi- Aventis, reference)	US Clopidogrel Tablets, 75 mg n=82 participants at risk Treatment C: a single oral dose of clopidogrel 75 mg film-coated tablet (Plavix®, Sanofi-Aventis, reference)	Total Number of Participants n=83 participants at risk total number of subjects exposed to any treatment
Nervous system disorders Headache	19.8% 16/81 • Number of events 19 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	18.8% 15/80 • Number of events 17 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	19.5% 16/82 • Number of events 20 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	34.9% 29/83 • Number of events 56 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Nervous system disorders Dizziness	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/80 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	3.7% 3/82 • Number of events 3 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	4.8% 4/83 • Number of events 4 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Nervous system disorders Presyncope	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/80 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/82 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Gastrointestinal disorders Abdominal Pain	1.2% 1/81 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/80 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/82 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	3.6% 3/83 • Number of events 3 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Gastrointestinal disorders Diarrhoea	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	50.0% 1/2 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	100.0% 2/2 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	75.0% 3/4 • Number of events 4 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Gastrointestinal disorders Nausea	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.4% 2/82 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.4% 2/83 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Gastrointestinal disorders Vomiting	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/82 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
General disorders Catheter Site Pain	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.5% 2/80 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/82 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.4% 2/83 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
General disorders Catheter Site Inflammation	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/82 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
General disorders Fatigue	1.2% 1/81 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/82 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Infections and infestations Nasopharyngitis	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.4% 2/82 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.4% 2/83 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Injury, poisoning and procedural complications Contusion	1.2% 1/81 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/82 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	2.4% 2/83 • Number of events 2 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/81 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/82 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/82 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets
Ear and labyrinth disorders Tinnitus	0.00% 0/81 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	0.00% 0/80 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/82 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets	1.2% 1/83 • Number of events 1 • From screening until follow-up, i.e. up to 7 weeks after the first dose. Adverse events (AEs) were assigned to the treatment after which they occurred: Treatment A: AEs starting at the time of /after dosing of European clopidogrel tablets Treatment B: AEs starting at the time of / after dosing of Japanese clopidogrel tablets Treatment C: AEs starting at the time of / after dosing of US clopidogrel tablets