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An Asian Study to Assess the Properties and Profile of Ticagrelor in Patients With Stable Coronary Artery Disease

A Randomised, Double-Blind, Parallel Group, Asian, Multicenter Study, to Assess Pharmacokinetic and Pharmacodynamic Profile of 2 Doses of Ticagrelor on Top of Low Dose Acetyl Salicylic Acid (ASA) Therapy on Platelet Aggregation in Japanese and Asian Patients With Stable Coronary Artery Disease

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01118325
Enrollment
146
Registered
2010-05-06
Start date
2010-04-30
Completion date
2011-03-31
Last updated
2014-07-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stable Coronary Artery Disease

Keywords

Stable Coronary Artery Disease, Platelet Aggregation

Brief summary

The purpose of the study is to determine the drug characteristics of Ticagrelor, and to determine if 4 weeks treatment will reduce the blood clotting.

Interventions

DRUGticagrelor

Drug oral treatment

DRUGclopidogrel

Drug oral treatment

Sponsors

AstraZeneca
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No

Inclusion criteria

* Any Percutaneous Coronary Intervention, more than 3 months prior to randomization * Previous documented acute coronary syndrome (ACS), more than 3 months prior to randomisation * Treatment with ASA

Exclusion criteria

* ACS, transient ischemic attack (TIA), or Stroke within the 3 months prior to randomisation * Known concurrent disease of stroke or TIA with atrial fibrillation * Persons who are being treated with blood clotting agents that cannot be stopped

Design outcomes

Primary

MeasureTime frameDescription
Inhibition of Platelet Aggregation(IPA) Final Extent at 2 Hours Post Dose on Week 4 in Japanese PatientsWeek 4Final extent IPA from pre-dose baseline was calculated using the following formula for Adenosine Diphosphate (ADP)-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) Platelet Aggregation (PA) was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
IPA Final Extent at 4 Hours Post Dose on Week 4 in Japanese PatientsWeek 4Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
IPA Final Extent at 8 Hours Post Dose on Week 4 in Japanese PatientsWeek 4Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
IPA Final Extent at 12 Hours Post Dose on Week 4 in Japanese PatientsWeek 4Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.
IPA Final Extent at 24 Hours Post Dose on Week 4 in Japanese PatientsWeek 4Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.

Secondary

MeasureTime frameDescription
AZD6140 (AUC0-tau) at Week 4Week 4Area under the plasma concentration curve of AZD6140 from time zero to dosing interval
AR-C124910XX (Tmax) at Week 4Week 4Time to reach peak or maximum concentration of AZD6140 drug metabolite AR-C124910XX following AZD6140 administration
AZD6140 (Cmax) at Week 4Week 4Maximum plasma AZD6140 concentration
AZD6140 (Tmax) at Week 4Week 4Time to reach peak or maximum concentration of AZD6140 following AZD6140 administration
AR-C124910XX (Cmax) at Week 4Week 4Maximum plasma concentration of AZD6140 drug metabolite AR-C124910XX
AR-C124910XX (AUC0-tau) at Week 4Week 4Area under the plasma concentration curve of AZD6140 drug metabolite AR-C124910XX from time zero to dosing interval

Countries

Japan, Philippines

Participant flow

Recruitment details

In total, 146 patients were enrolled at 15 sites from 2 countries (Japan and Philippines). The study period was from April 2010 to March 2011. In total, 139 subjects were randomised and received the investigational product. Most subjects completed the study but 2 Japanese patients discontinued due to an AE during the 4 weeks treatment period.

Participants by arm

ArmCount
AZD6140 45 mg bd
AZD6140 45 mg twice daily
50
AZD6140 90 mg bd
AZD6140 90 mg twice daily
43
Clopidogrel 75 mg od
Clopidogrel 75 mg once daily
46
Total139

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyAdverse Event101

Baseline characteristics

CharacteristicAZD6140 45 mg bdAZD6140 90 mg bdClopidogrel 75 mg odTotal
Age, Continuous63 Years
STANDARD_DEVIATION 11
64 Years
STANDARD_DEVIATION 9
64 Years
STANDARD_DEVIATION 10
63 Years
STANDARD_DEVIATION 10
Race/Ethnicity, Customized
Japanese
42 Participants35 Participants40 Participants117 Participants
Race/Ethnicity, Customized
Non-Japanese
8 Participants8 Participants6 Participants22 Participants
Sex: Female, Male
Female
4 Participants3 Participants8 Participants15 Participants
Sex: Female, Male
Male
46 Participants40 Participants38 Participants124 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
13 / 5023 / 439 / 46
serious
Total, serious adverse events
2 / 501 / 430 / 46

Outcome results

Primary

Inhibition of Platelet Aggregation(IPA) Final Extent at 2 Hours Post Dose on Week 4 in Japanese Patients

Final extent IPA from pre-dose baseline was calculated using the following formula for Adenosine Diphosphate (ADP)-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) Platelet Aggregation (PA) was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.

Time frame: Week 4

Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan

ArmMeasureValue (MEAN)Dispersion
AZD6140 45 mg bdInhibition of Platelet Aggregation(IPA) Final Extent at 2 Hours Post Dose on Week 4 in Japanese Patients64.5 percentage inhibitionStandard Deviation 14.8
AZD6140 90 mg bdInhibition of Platelet Aggregation(IPA) Final Extent at 2 Hours Post Dose on Week 4 in Japanese Patients73.0 percentage inhibitionStandard Deviation 14.2
Clopidogrel 75 mg odInhibition of Platelet Aggregation(IPA) Final Extent at 2 Hours Post Dose on Week 4 in Japanese Patients38.9 percentage inhibitionStandard Deviation 20.7
Primary

IPA Final Extent at 12 Hours Post Dose on Week 4 in Japanese Patients

Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.

Time frame: Week 4

Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan

ArmMeasureValue (MEAN)Dispersion
AZD6140 45 mg bdIPA Final Extent at 12 Hours Post Dose on Week 4 in Japanese Patients56.9 percentage inhibitionStandard Deviation 20.9
AZD6140 90 mg bdIPA Final Extent at 12 Hours Post Dose on Week 4 in Japanese Patients66.8 percentage inhibitionStandard Deviation 20.1
Clopidogrel 75 mg odIPA Final Extent at 12 Hours Post Dose on Week 4 in Japanese Patients41.8 percentage inhibitionStandard Deviation 21.7
Primary

IPA Final Extent at 24 Hours Post Dose on Week 4 in Japanese Patients

Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.

Time frame: Week 4

Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan

ArmMeasureValue (MEAN)Dispersion
AZD6140 45 mg bdIPA Final Extent at 24 Hours Post Dose on Week 4 in Japanese Patients46.2 percentage inhibitionStandard Deviation 23.3
AZD6140 90 mg bdIPA Final Extent at 24 Hours Post Dose on Week 4 in Japanese Patients59.1 percentage inhibitionStandard Deviation 20.3
Clopidogrel 75 mg odIPA Final Extent at 24 Hours Post Dose on Week 4 in Japanese Patients38.0 percentage inhibitionStandard Deviation 20.5
Primary

IPA Final Extent at 4 Hours Post Dose on Week 4 in Japanese Patients

Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.

Time frame: Week 4

Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan

ArmMeasureValue (MEAN)Dispersion
AZD6140 45 mg bdIPA Final Extent at 4 Hours Post Dose on Week 4 in Japanese Patients67.3 percentage inhibitionStandard Deviation 15.6
AZD6140 90 mg bdIPA Final Extent at 4 Hours Post Dose on Week 4 in Japanese Patients73.2 percentage inhibitionStandard Deviation 15.1
Clopidogrel 75 mg odIPA Final Extent at 4 Hours Post Dose on Week 4 in Japanese Patients43.7 percentage inhibitionStandard Deviation 20.6
Primary

IPA Final Extent at 8 Hours Post Dose on Week 4 in Japanese Patients

Final extent IPA from pre-dose baseline was calculated using the following formula for ADP-induced platelet aggregation: Percentage Inhibition = 100% x (PAs - PA) / (PAs) PA was the mean response at the given post dose time point and PAs was the mean response at pre dose baseline. Percentage inhibition was restricted to the closed interval \[0,100\]; any data falling outside this range was truncated to the appropriate limit.

Time frame: Week 4

Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis. Arm AZD6140 90 mg bd includes one non-Japanese participant resident in Japan

ArmMeasureValue (MEAN)Dispersion
AZD6140 45 mg bdIPA Final Extent at 8 Hours Post Dose on Week 4 in Japanese Patients62.7 percentage inhibitionStandard Deviation 17.7
AZD6140 90 mg bdIPA Final Extent at 8 Hours Post Dose on Week 4 in Japanese Patients68.6 percentage inhibitionStandard Deviation 16
Clopidogrel 75 mg odIPA Final Extent at 8 Hours Post Dose on Week 4 in Japanese Patients42.5 percentage inhibitionStandard Deviation 20.2
Secondary

AR-C124910XX (AUC0-tau) at Week 4

Area under the plasma concentration curve of AZD6140 drug metabolite AR-C124910XX from time zero to dosing interval

Time frame: Week 4

Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
AZD6140 45 mg bdAR-C124910XX (AUC0-tau) at Week 41180 ng.h/mLStandard Deviation 490
AZD6140 90 mg bdAR-C124910XX (AUC0-tau) at Week 4954 ng.h/mLStandard Deviation 741
Clopidogrel 75 mg odAR-C124910XX (AUC0-tau) at Week 42720 ng.h/mLStandard Deviation 915
AZD6140 90 mg bd in Non-Japanese PatientsAR-C124910XX (AUC0-tau) at Week 43380 ng.h/mLStandard Deviation 1580
Secondary

AR-C124910XX (Cmax) at Week 4

Maximum plasma concentration of AZD6140 drug metabolite AR-C124910XX

Time frame: Week 4

Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
AZD6140 45 mg bdAR-C124910XX (Cmax) at Week 4135 ng/mLStandard Deviation 53.3
AZD6140 90 mg bdAR-C124910XX (Cmax) at Week 4101 ng/mLStandard Deviation 72.4
Clopidogrel 75 mg odAR-C124910XX (Cmax) at Week 4326 ng/mLStandard Deviation 139
AZD6140 90 mg bd in Non-Japanese PatientsAR-C124910XX (Cmax) at Week 4381 ng/mLStandard Deviation 192
Secondary

AR-C124910XX (Tmax) at Week 4

Time to reach peak or maximum concentration of AZD6140 drug metabolite AR-C124910XX following AZD6140 administration

Time frame: Week 4

Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.

ArmMeasureValue (MEDIAN)
AZD6140 45 mg bdAR-C124910XX (Tmax) at Week 44.0 hour
AZD6140 90 mg bdAR-C124910XX (Tmax) at Week 44.0 hour
Clopidogrel 75 mg odAR-C124910XX (Tmax) at Week 42.1 hour
AZD6140 90 mg bd in Non-Japanese PatientsAR-C124910XX (Tmax) at Week 42.0 hour
Secondary

AZD6140 (AUC0-tau) at Week 4

Area under the plasma concentration curve of AZD6140 from time zero to dosing interval

Time frame: Week 4

Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
AZD6140 45 mg bdAZD6140 (AUC0-tau) at Week 43050 ng.h/mLStandard Deviation 1940
AZD6140 90 mg bdAZD6140 (AUC0-tau) at Week 42930 ng.h/mLStandard Deviation 3740
Clopidogrel 75 mg odAZD6140 (AUC0-tau) at Week 46080 ng.h/mLStandard Deviation 2600
AZD6140 90 mg bd in Non-Japanese PatientsAZD6140 (AUC0-tau) at Week 410900 ng.h/mLStandard Deviation 2790
Secondary

AZD6140 (Cmax) at Week 4

Maximum plasma AZD6140 concentration

Time frame: Week 4

Population: Only Japanese participants who had IPA data at Week 4 were considered in this analysis

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
AZD6140 45 mg bdAZD6140 (Cmax) at Week 4422 ng/mLStandard Deviation 230
AZD6140 90 mg bdAZD6140 (Cmax) at Week 4341 ng/mLStandard Deviation 370
Clopidogrel 75 mg odAZD6140 (Cmax) at Week 4931 ng/mLStandard Deviation 442
AZD6140 90 mg bd in Non-Japanese PatientsAZD6140 (Cmax) at Week 41380 ng/mLStandard Deviation 343
Secondary

AZD6140 (Tmax) at Week 4

Time to reach peak or maximum concentration of AZD6140 following AZD6140 administration

Time frame: Week 4

Population: In total 7 Japanese patients (4 patients in 45 mg and 3 patients in 90 mg) were excluded from the PK analysis set since PK samples of these patients were discarded due to a database set-up issue at the central laboratory.

ArmMeasureValue (MEDIAN)
AZD6140 45 mg bdAZD6140 (Tmax) at Week 42.0 hour
AZD6140 90 mg bdAZD6140 (Tmax) at Week 44.0 hour
Clopidogrel 75 mg odAZD6140 (Tmax) at Week 42.0 hour
AZD6140 90 mg bd in Non-Japanese PatientsAZD6140 (Tmax) at Week 44.0 hour

Source: ClinicalTrials.gov · Data processed: Mar 9, 2026