Ticagrelor China Pharmacokinetic/Pharmacodynamic Study

An Open Label, Single Centre, Randomised, Phase IV, Pharmacokinetic, Pharmacodynamic, and Safety Study to Evaluate Single and Multiple Doses of 45, 60, and 90 mg of Ticagrelor in Chinese Patients With Stable Coronary Heart Disease

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02064985

Enrollment

Registered

2014-02-17

Start date

2014-02-28

Completion date

2014-11-30

Last updated

2016-05-11

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

Conditions

Stable Coronary Heart Disease (CHD)

Brief summary

open label, single centre, randomised, Phase IV, pharmacokinetic, pharmacodynamic, and safety study to evaluate single and multiple doses of 45, 60, and 90 mg of ticagrelor in Chinese patients with stable coronary heart disease

Detailed description

Up to 36 patients will be randomized in order to ensure 10 patients per treatment are evaluable.Ticagrelor will be supplied as 45 mg, 60mg, and 90mg tablets. Following an 8 hour fast on single dose on Day 1 and Day 7; on multiple doses from Day 3 to Day 6. Prior to the first dose of study drug there will be a screening period of maximum of 19 days. Patients will report to the clinical pharmacology unit (CPU) on Day -2 and will remain confined there until completion of study procedures on Day 7, the patients will be discharged on Day 8. In addition, patients will return to the CPU for a follow up visit 2 to 5 days after the last dose. Each patients participation, including the screening period, will take approximately 33 days.

Interventions

DRUGInhibition of Platelet Aggregation by Brilinta(Ticagrelor)

To determine the Inhibition of Platelet Aggregation (IPA) profiles of single and multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease (CHD) on chronic low dose ASA (75-100mg daily).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Provision of signed and dated written informed consent prior to any study specific procedures. 2. Female or male Chinese (as defined by Chinese Regulatory) patients aged 18 years or older with suitable veins for cannulations or repeated venipunctures. 3. Documented stable coronary heart disease (CHD) fulfilling all of the following, and taking 75-100 mg ASA daily treatment: Diagnosed stable angina pectoris per the guidance of Chinese Society of Cardiology published in 2007, patients with angina severity classified as I and II of Canadian Cardiovascular Society grading of angina pectoris. 4. Female patients without pregnant potential

Exclusion criteria

1. Any indication for oral anticoagulant or dual antiplatelet treatment and chronic ASA with doses greater than 100 mg/day. 2. Concomitant therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic index, or strong CYP3A inducers within 14 days preceding the first dose of study medication and during study treatment. 3. Increased bleeding risk. 4. Contraindication or other reason that ASA or ticagrelor should not be administered 5. Patients that are scheduled for revascularization (eg, PCI, CABG) during the study period

Design outcomes

Primary

Measure	Time frame	Description
IPA on Day 1	Baseline and at 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 36 hours,48 hours after dose intake on Day 1	The Inhibition of Platelet Aggregation (IPA) profiles of single and multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease (CHD) on chronic low dose ASA (75-100mg daily). Primary variable: IPA (final extent) induced by 20µM ADP at each assessment point after single and multiple doses of ticagrelor measured by Light-Transmittance Aggregometry (LTA).
IPA on Day 7	Baseline and at 0 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours after dose intake on Day 7	The inhibition of Platelet Aggregation (IPA) profiles of single and multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease (CHD) on chronic low dose ASA (75-100mg daily). Primary variable: IPA (final extent) induced by 20µM ADP at each assessment point after single and multiple doses of ticagrelor measured by Light-Transmittance Aggregometry (LTA).

Secondary

Measure	Time frame	Description
Safety---Vital Signs Over Time---Blood Pressure	Baseline, Day 1 to Day 7 and 2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Vital signs (seated blood pressure \[BP\])
Percent Change From Baseline in PRU on Day 7	Baseline and at 0 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours after dose intake on Day 7	Percent Change from baseline in Platelet P2Y12 Reaction Units (PRU)(measured by VerifyNow) profiles of multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease on chronic low dose ASA.
TIPA(Max)---Day 1	Day 1	The time to peak IPA (TIPAmax) was estimated for ADP-induced final extent IPA.
TIPA(Max)---Day 7	Day 7	The time to peak IPA (TIPAmax) was estimated for ADP-induced final extent IPA.
AUEC(Final Extent) on Day 1	IPA was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	The area-under-the-effect curve (AUEC) was estimated for ADP-induced final extent IPA.
AUEC(Final Extent) on Day 7	IPA was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	The area-under-the-effect curve (AUEC) was estimated for ADP-induced final extent IPA.
Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	The pharmacokinetics parameter of ticagrelor on Day 1---tmax and t1/2
Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	The pharmacokinetics parameters of Ticagrelor on Day 1---AUC(0-inf), AUC(0-12h) and AUC(0-t).
Pharmacokinetics Parameters of Ticagrelor on Day 7(2)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	The pharmacokinetics parameters of ticagrelor on Day 7---tmax
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(1)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 1---Cmax
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 1: tmax and t1/2
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(1)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of Metabolite (AR-C124910XX) on Day 7---Cmax
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(4)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 7---tmax
Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax	Day 1	To determine Cmax ratio for the metabolite to that of the parent compound on Day 1
Pharmacokinetics Parameters of Metabolite : Parent on Day 7---Cmax	Day 7	To determine Cmax ratio of metabolite to that of the parent compound on Day 7
Safety---Physical Examination, Summary of Abnormalities	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Physical examination
Safety---Hematology Laboratory Variables Over Time---hematocrit	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Haematology---hematocrit
Safety---All Allowed Concomitant Medications During Study Treatment	All allowed concomitant medications during study treatment(up to 2-5 days after last dose), includes medications that began prior to randomization but were ongoing after randomization.	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Concomitant medications
Safety---Causally Related Adverse Events by System Organ Class and Preferred Term	Includes adverse events with an onset date on or after the date of first dose and up to and including the last study visit (up to 2-5 days after last dose).	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Assessment of adverse events
Pharmacokinetics Parameters of Ticagrelor on Day 1(1)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	The pharmacokinetics parameters of Ticagrelor on Day 1---Cmax
Pharmacokinetics Parameters of Ticagrelor on Day 7(3)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of Ticagrelor on Day 7---AUC(0-12h)
Pharmacokinetics Parameters of Ticagrelor on Day 7(4)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of Ticagrelor on Day 7---Accumulation ratio(ratio of Day 7 AUC(0-12h) to Day 1 AUC(0-12h))
Safety---Vital Signs Over Time---Height	Baseline	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Vital signs (Height)
Safety---Vital Signs Over Time---Weight	Baseline	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Vital signs (Weight)
Safety---Vital Signs Over Time---Pulse Rate	Baseline, Day 1 to Day 7 and 2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Vital signs (Pulse Rate)
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1	Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 1---AUC(0-12h), AUC(0-t) and AUC(0-inf)
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(2)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of Metabolite (AR-C124910XX) on Day 7---AUC(0-12h)
Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(3)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of Metabolite (AR-C124910XX) on Day 7---Accumulation ratio(ratio of Day 7 AUC(0-12h) to Day 1 AUC(0-12h))
Safety---Hematology Laboratory Variables Over Time---Erythrocytes	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Haematology---Erythrocytes
Safety---Hematology Laboratory Variables Over Time---Hemoglobin	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Haematology---Hemoglobin
Safety---Hematology Laboratory Variables Over Time---Leukocytes	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Haematology---Leukocytes
Safety---Hematology Laboratory Variables Over Time---Platelets	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Haematology---Platelets
Safety---Clinical Chemistry Variables Over Time---Glucose	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Glucose
Safety---Clinical Chemistry Variables Over Time---Alanine Aminotransferase	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Alanine Aminotransferase
Safety---Clinical Chemistry Variables Over Time---Aspartate Aminotransferase	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Aspartate Aminotransferase
Safety---Clinical Chemistry Variables Over Time---Alkaline Phosphatase	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Alkaline Phosphatase
Safety---Clinical Chemistry Variables Over Time---Creatinine	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Creatinine
Safety---Clinical Chemistry Variables Over Time---Total Bilirubin	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Total Bilirubin
Safety---Clinical Chemistry Variables Over Time---Sodium	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Sodium
Safety---Clinical Chemistry Variables Over Time---Potassium	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Potassium
Safety---Clinical Chemistry Variables Over Time---Chloride	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Chloride
Safety---Clinical Chemistry Variables Over Time---Phosphate	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Phosphate
Safety---Clinical Chemistry Variables Over Time---Albumin	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Albumin
Percent Change From Baseline in PRU on Day 1	Baseline and at 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 36 hours,48 hours after dose intake on Day 1	Percent Change from baseline in Platelet P2Y12 Reaction Units (PRU)(measured by VerifyNow) profiles of multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease on chronic low dose ASA.
Safety---Clinical Chemistry Variables Over Time---Blood Urea Nitrogen	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Blood Urea Nitrogen
Safety---Clinical Chemistry Variables Over Time---Bicarbonate	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Bicarbonate
Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)	Day 1	To determine AUC(0-inf) ratio for the metabolite to that of the parent compound on Day 1
Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)	Day 7	To determine AUC(0-12h) ratio of metabolite to that of the parent compound on Day 7.
Safety---Clinical Chemistry Variables Over Time---Protein	2 to 5 days after last dose	The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Clinical Chemistry---Protein
Pharmacokinetics Parameters of Ticagrelor on Day 7(1)	Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7	Pharmacokinetics parameters of Ticagrelor on Day 7---Cmax

Countries

China

Participant flow

Recruitment details

The first patient was recruited on February 27th 2014 and the last patient's informed consent was obtained on Oct 24th 2014.

Pre-assignment details

22 participants did not meet includion/exclusion criteria. 2 participants withdrawed from study due to subject decision.1 participant withdrawed due to other reason. 36 participants were randomized and received study medication.

Participants by arm

Arm	Count
Ticagrelor 45mg A single dose of ticagrelor 45 mg on Day 1 followed by 45 mg twice daily (bid) on Days 3-6 and a 45mg single dose on Day 7.	12
Ticagrelor 60mg A single dose of ticagrelor 60 mg on Day 1 followed by 60 mg twice daily (bid) on Days 3-6 and a 60mg single dose on Day 7.	12
Ticagrelor 90mg A single dose of ticagrelor 90 mg on Day 1 followed by 90 mg twice daily (bid) on Days 3-6 and a 90mg single dose on Day 7.	12
Total	36

Baseline characteristics

Characteristic	Ticagrelor 45mg	Ticagrelor 60mg	Ticagrelor 90mg	Total
Age, Continuous	59.3 years STANDARD_DEVIATION 9.8	61.3 years STANDARD_DEVIATION 7	57.9 years STANDARD_DEVIATION 12.6	59.5 years STANDARD_DEVIATION 9.9
Age, Customized < 65 years	9 Participants	8 Participants	8 Participants	25 Participants
Age, Customized >=65 years	3 Participants	4 Participants	4 Participants	11 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants	12 Participants	12 Participants	36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	12 Participants	12 Participants	12 Participants	36 Participants
Sex: Female, Male Female	3 Participants	2 Participants	3 Participants	8 Participants
Sex: Female, Male Male	9 Participants	10 Participants	9 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	4 / 12	4 / 12	5 / 12
serious Total, serious adverse events	0 / 12	0 / 12	0 / 12

Outcome results

Primary

IPA on Day 1

The Inhibition of Platelet Aggregation (IPA) profiles of single and multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease (CHD) on chronic low dose ASA (75-100mg daily). Primary variable: IPA (final extent) induced by 20µM ADP at each assessment point after single and multiple doses of ticagrelor measured by Light-Transmittance Aggregometry (LTA).

Time frame: Baseline and at 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 36 hours,48 hours after dose intake on Day 1

Population: All randomly assigned patients who received at least 1 dose of ticagrelor with post-dose PD measurements available and no protocol deviation considered to significantly affect the integrity of PD results (eg, non-compliance with study drug).

Arm	Measure	Group	Value (MEAN)	Dispersion
Ticagrelor 45mg	IPA on Day 1	3 hours after dose intake	88.44 % IPA	Standard Deviation 11.786
Ticagrelor 45mg	IPA on Day 1	48 hours after dose intake	23.56 % IPA	Standard Deviation 22.956
Ticagrelor 45mg	IPA on Day 1	12 hours after dose intake	71.25 % IPA	Standard Deviation 16.518
Ticagrelor 45mg	IPA on Day 1	6 hours after dose intake	85.02 % IPA	Standard Deviation 8.965
Ticagrelor 45mg	IPA on Day 1	0.5 hour after dose intake	27.09 % IPA	Standard Deviation 25.956
Ticagrelor 45mg	IPA on Day 1	36 hours after dose intake	40.09 % IPA	Standard Deviation 28.211
Ticagrelor 45mg	IPA on Day 1	2 hours after dose intake	82.24 % IPA	Standard Deviation 21.16
Ticagrelor 45mg	IPA on Day 1	1 hour after dose intake	57.20 % IPA	Standard Deviation 26.563
Ticagrelor 45mg	IPA on Day 1	24 hours after dose intake	44.11 % IPA	Standard Deviation 34.165
Ticagrelor 60mg	IPA on Day 1	6 hours after dose intake	94.32 % IPA	Standard Deviation 6.243
Ticagrelor 60mg	IPA on Day 1	0.5 hour after dose intake	25.87 % IPA	Standard Deviation 27.036
Ticagrelor 60mg	IPA on Day 1	1 hour after dose intake	50.97 % IPA	Standard Deviation 32.747
Ticagrelor 60mg	IPA on Day 1	2 hours after dose intake	84.10 % IPA	Standard Deviation 17.645
Ticagrelor 60mg	IPA on Day 1	3 hours after dose intake	90.18 % IPA	Standard Deviation 9.232
Ticagrelor 60mg	IPA on Day 1	12 hours after dose intake	85.70 % IPA	Standard Deviation 15.237
Ticagrelor 60mg	IPA on Day 1	24 hours after dose intake	49.38 % IPA	Standard Deviation 25.153
Ticagrelor 60mg	IPA on Day 1	36 hours after dose intake	46.23 % IPA	Standard Deviation 17.352
Ticagrelor 60mg	IPA on Day 1	48 hours after dose intake	27.25 % IPA	Standard Deviation 17.993
Ticagrelor 90mg	IPA on Day 1	2 hours after dose intake	86.11 % IPA	Standard Deviation 22.213
Ticagrelor 90mg	IPA on Day 1	0.5 hour after dose intake	33.34 % IPA	Standard Deviation 31.238
Ticagrelor 90mg	IPA on Day 1	24 hours after dose intake	66.48 % IPA	Standard Deviation 21.2
Ticagrelor 90mg	IPA on Day 1	1 hour after dose intake	61.64 % IPA	Standard Deviation 31.244
Ticagrelor 90mg	IPA on Day 1	48 hours after dose intake	43.04 % IPA	Standard Deviation 25.178
Ticagrelor 90mg	IPA on Day 1	6 hours after dose intake	94.02 % IPA	Standard Deviation 6.19
Ticagrelor 90mg	IPA on Day 1	3 hours after dose intake	96.24 % IPA	Standard Deviation 6.396
Ticagrelor 90mg	IPA on Day 1	36 hours after dose intake	55.64 % IPA	Standard Deviation 29.446
Ticagrelor 90mg	IPA on Day 1	12 hours after dose intake	90.70 % IPA	Standard Deviation 8.117

Primary

IPA on Day 7

The inhibition of Platelet Aggregation (IPA) profiles of single and multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease (CHD) on chronic low dose ASA (75-100mg daily). Primary variable: IPA (final extent) induced by 20µM ADP at each assessment point after single and multiple doses of ticagrelor measured by Light-Transmittance Aggregometry (LTA).

Time frame: Baseline and at 0 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours after dose intake on Day 7

Arm	Measure	Group	Value (MEAN)	Dispersion
Ticagrelor 45mg	IPA on Day 7	0 hour after dose intake	79.69 % IPA	Standard Deviation 20.547
Ticagrelor 45mg	IPA on Day 7	3 hours after dose intake	91.00 % IPA	Standard Deviation 13.212
Ticagrelor 45mg	IPA on Day 7	1 hour after dose intake	88.82 % IPA	Standard Deviation 15.639
Ticagrelor 45mg	IPA on Day 7	2 hours after dose intake	88.30 % IPA	Standard Deviation 17.325
Ticagrelor 45mg	IPA on Day 7	12 hours after dose intake	86.55 % IPA	Standard Deviation 16.918
Ticagrelor 45mg	IPA on Day 7	6 hours after dose intake	91.13 % IPA	Standard Deviation 14.344
Ticagrelor 45mg	IPA on Day 7	0.5 hour after dose intake	84.70 % IPA	Standard Deviation 15.998
Ticagrelor 60mg	IPA on Day 7	1 hour after dose intake	93.28 % IPA	Standard Deviation 7.589
Ticagrelor 60mg	IPA on Day 7	2 hours after dose intake	94.62 % IPA	Standard Deviation 3.787
Ticagrelor 60mg	IPA on Day 7	0 hour after dose intake	89.26 % IPA	Standard Deviation 7.857
Ticagrelor 60mg	IPA on Day 7	0.5 hour after dose intake	89.96 % IPA	Standard Deviation 7.985
Ticagrelor 60mg	IPA on Day 7	3 hours after dose intake	97.01 % IPA	Standard Deviation 2.258
Ticagrelor 60mg	IPA on Day 7	6 hours after dose intake	92.94 % IPA	Standard Deviation 17.847
Ticagrelor 60mg	IPA on Day 7	12 hours after dose intake	92.01 % IPA	Standard Deviation 7.316
Ticagrelor 90mg	IPA on Day 7	3 hours after dose intake	98.86 % IPA	Standard Deviation 2.664
Ticagrelor 90mg	IPA on Day 7	0 hour after dose intake	95.10 % IPA	Standard Deviation 6.91
Ticagrelor 90mg	IPA on Day 7	12 hours after dose intake	96.81 % IPA	Standard Deviation 4.219
Ticagrelor 90mg	IPA on Day 7	6 hours after dose intake	98.87 % IPA	Standard Deviation 2.598
Ticagrelor 90mg	IPA on Day 7	1 hour after dose intake	96.47 % IPA	Standard Deviation 4.184
Ticagrelor 90mg	IPA on Day 7	0.5 hour after dose intake	96.90 % IPA	Standard Deviation 3.602
Ticagrelor 90mg	IPA on Day 7	2 hours after dose intake	98.29 % IPA	Standard Deviation 3.526

Secondary

AUEC(Final Extent) on Day 1

The area-under-the-effect curve (AUEC) was estimated for ADP-induced final extent IPA.

Time frame: IPA was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Arm	Measure	Value (MEAN)	Dispersion
Ticagrelor 45mg	AUEC(Final Extent) on Day 1	2474.4 %*h	Standard Deviation 949.3
Ticagrelor 60mg	AUEC(Final Extent) on Day 1	2819.4 %*h	Standard Deviation 707.17
Ticagrelor 90mg	AUEC(Final Extent) on Day 1	3301.0 %*h	Standard Deviation 788.72

Secondary

AUEC(Final Extent) on Day 7

The area-under-the-effect curve (AUEC) was estimated for ADP-induced final extent IPA.

Time frame: IPA was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (MEAN)	Dispersion
Ticagrelor 45mg	AUEC(Final Extent) on Day 7	1069.9 %*h	Standard Deviation 176.89
Ticagrelor 60mg	AUEC(Final Extent) on Day 7	1120.1 %*h	Standard Deviation 108.44
Ticagrelor 90mg	AUEC(Final Extent) on Day 7	1176.9 %*h	Standard Deviation 33.03

Secondary

Percent Change From Baseline in PRU on Day 1

Percent Change from baseline in Platelet P2Y12 Reaction Units (PRU)(measured by VerifyNow) profiles of multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease on chronic low dose ASA.

Time frame: Baseline and at 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 24 hours, 36 hours,48 hours after dose intake on Day 1

Population: All randomized patients who received at least one dose of investigational product with post-dose PD measurements available and no protocol deviation considered to significantly affect the integrity of PD results (e.g., non-compliance with study drug) will be included in the PD analysis set.

Arm	Measure	Group	Value (MEAN)	Dispersion
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	3 hours after dose intake	-71.58 % change from baseline	Standard Deviation 22.22
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	48hours after dose intake	-15.19 % change from baseline	Standard Deviation 23.331
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	12 hours after dose intake	-41.93 % change from baseline	Standard Deviation 23.584
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	6 hours after dose intake	-60.27 % change from baseline	Standard Deviation 25.208
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	0.5 hour after dose intake	-19.20 % change from baseline	Standard Deviation 13.712
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	36 hours after dose intake	-9.57 % change from baseline	Standard Deviation 17.655
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	2 hours after dose intake	-72.60 % change from baseline	Standard Deviation 16.492
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	1 hour after dose intake	-60.00 % change from baseline	Standard Deviation 27.295
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 1	24 hours after dose intake	-35.94 % change from baseline	Standard Deviation 20.706
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	6 hours after dose intake	-67.98 % change from baseline	Standard Deviation 16.709
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	0.5 hour after dose intake	-13.76 % change from baseline	Standard Deviation 22.786
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	1 hour after dose intake	-35.25 % change from baseline	Standard Deviation 28.795
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	2 hours after dose intake	-61.23 % change from baseline	Standard Deviation 23.304
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	3 hours after dose intake	-75.42 % change from baseline	Standard Deviation 15.315
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	12 hours after dose intake	-47.15 % change from baseline	Standard Deviation 20.31
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	24 hours after dose intake	-28.34 % change from baseline	Standard Deviation 19.865
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	36 hours after dose intake	-1.91 % change from baseline	Standard Deviation 18.12
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 1	48hours after dose intake	-0.57 % change from baseline	Standard Deviation 13.07
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	2 hours after dose intake	-78.85 % change from baseline	Standard Deviation 18.775
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	0.5 hour after dose intake	-19.59 % change from baseline	Standard Deviation 23.88
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	24 hours after dose intake	-54.61 % change from baseline	Standard Deviation 19.553
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	1 hour after dose intake	-67.70 % change from baseline	Standard Deviation 30.613
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	48hours after dose intake	-16.38 % change from baseline	Standard Deviation 18.164
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	6 hours after dose intake	-81.08 % change from baseline	Standard Deviation 11.024
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	3 hours after dose intake	-87.97 % change from baseline	Standard Deviation 11.134
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	36 hours after dose intake	-22.59 % change from baseline	Standard Deviation 24.694
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 1	12 hours after dose intake	-73.47 % change from baseline	Standard Deviation 13.705

Secondary

Percent Change From Baseline in PRU on Day 7

Time frame: Baseline and at 0 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours after dose intake on Day 7

Arm	Measure	Group	Value (MEAN)	Dispersion
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 7	0.5 hour after dose intake	-77.90 % change from baseline	Standard Deviation 17.632
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 7	1 hour after dose intake	-79.70 % change from baseline	Standard Deviation 17.742
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 7	2 hours after dose intake	-82.23 % change from baseline	Standard Deviation 17.304
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 7	3 hours after dose intake	-79.98 % change from baseline	Standard Deviation 18.434
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 7	6 hours after dose intake	-76.71 % change from baseline	Standard Deviation 20.067
Ticagrelor 45mg	Percent Change From Baseline in PRU on Day 7	12 hours after dose intake	-63.63 % change from baseline	Standard Deviation 23.767
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 7	12 hours after dose intake	-69.03 % change from baseline	Standard Deviation 19.867
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 7	0.5 hour after dose intake	-80.07 % change from baseline	Standard Deviation 14.691
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 7	3 hours after dose intake	-86.96 % change from baseline	Standard Deviation 12.868
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 7	6 hours after dose intake	-75.07 % change from baseline	Standard Deviation 14.806
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 7	1 hour after dose intake	-78.40 % change from baseline	Standard Deviation 18.103
Ticagrelor 60mg	Percent Change From Baseline in PRU on Day 7	2 hours after dose intake	-85.00 % change from baseline	Standard Deviation 12.02
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 7	1 hour after dose intake	-94.10 % change from baseline	Standard Deviation 6.746
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 7	2 hours after dose intake	-88.81 % change from baseline	Standard Deviation 13.595
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 7	12 hours after dose intake	-88.60 % change from baseline	Standard Deviation 8.816
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 7	3 hours after dose intake	-92.13 % change from baseline	Standard Deviation 9.288
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 7	0.5 hour after dose intake	-89.33 % change from baseline	Standard Deviation 8.923
Ticagrelor 90mg	Percent Change From Baseline in PRU on Day 7	6 hours after dose intake	-91.48 % change from baseline	Standard Deviation 7.928

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(1)

Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 1---Cmax

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Population: All randomized patients who received at least one dose of investigational product with post-dose PK measurements available and no protocol deviation considered to significantly affect PK of ticagrelor and its metabolite, AR C124910XX, will be included in the PK analysis set.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(1)	88.28 ng/mL	Geometric Coefficient of Variation 24.58
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(1)	77.11 ng/mL	Geometric Coefficient of Variation 53.92
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(1)	138.6 ng/mL	Geometric Coefficient of Variation 38.37

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)

Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 1---AUC(0-12h), AUC(0-t) and AUC(0-inf)

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-t)	839.6 h*ng/mL	Geometric Coefficient of Variation 25.23
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-inf)	921.5 h*ng/mL	Geometric Coefficient of Variation 28.66
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-12h)	464.0 h*ng/mL	Geometric Coefficient of Variation 19.11
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-t)	906.0 h*ng/mL	Geometric Coefficient of Variation 56.84
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-inf)	1108 h*ng/mL	Geometric Coefficient of Variation 34.83
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-12h)	504.1 h*ng/mL	Geometric Coefficient of Variation 55.41
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-inf)	1644 h*ng/mL	Geometric Coefficient of Variation 30.83
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-12h)	835.9 h*ng/mL	Geometric Coefficient of Variation 29.59
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)	AUC(0-t)	1534 h*ng/mL	Geometric Coefficient of Variation 28.88

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)

Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 1: tmax and t1/2

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Arm	Measure	Group	Value (MEDIAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	tmax	2.00 hour	Full Range 38.02
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	t½	13.16 hour	Full Range 51.42
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	tmax	3.00 hour	Full Range 34.14
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	t½	11.64 hour	Full Range 32.46
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	tmax	3.00 hour	Full Range 37.39
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)	t½	11.29 hour	Full Range 53.84

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(1)

Pharmacokinetics parameters of Metabolite (AR-C124910XX) on Day 7---Cmax

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(1)	143.7 ng/mL	Geometric Coefficient of Variation 26.32
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(1)	180.1 ng/mL	Geometric Coefficient of Variation 49.83
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(1)	300.6 ng/mL	Geometric Coefficient of Variation 31.74

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(2)

Pharmacokinetics parameters of Metabolite (AR-C124910XX) on Day 7---AUC(0-12h)

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(2)	1069 h*ng/mL	Geometric Coefficient of Variation 24.89
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(2)	1314 h*ng/mL	Geometric Coefficient of Variation 41.02
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(2)	2254 h*ng/mL	Geometric Coefficient of Variation 37.02

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(3)

Pharmacokinetics parameters of Metabolite (AR-C124910XX) on Day 7---Accumulation ratio(ratio of Day 7 AUC(0-12h) to Day 1 AUC(0-12h))

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(3)	2.304 ratio	Geometric Coefficient of Variation 24.7
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(3)	2.606 ratio	Geometric Coefficient of Variation 28.34
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(3)	2.697 ratio	Geometric Coefficient of Variation 27.42

Secondary

Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(4)

Pharmacokinetics parameters of AR-C124910XX (active metabolite) on Day 7---tmax

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (MEDIAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(4)	2.00 hour	Full Range 38.02
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(4)	2.00 hour	Full Range 34.14
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(4)	2.54 hour	Full Range 37.39

Secondary

Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)

To determine AUC(0-inf) ratio for the metabolite to that of the parent compound on Day 1

Time frame: Day 1

Arm	Measure	Value (MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)	0.3310 ratio	Standard Deviation 0.09838
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)	0.3403 ratio	Standard Deviation 0.07381
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)	0.3106 ratio	Standard Deviation 0.1283

Secondary

Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax

To determine Cmax ratio for the metabolite to that of the parent compound on Day 1

Time frame: Day 1

Arm	Measure	Value (MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax	0.2277 ratio	Standard Deviation 0.08984
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax	0.2146 ratio	Standard Deviation 0.06333
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax	0.2005 ratio	Standard Deviation 0.08334

Secondary

Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)

To determine AUC(0-12h) ratio of metabolite to that of the parent compound on Day 7.

Time frame: Day 7

Arm	Measure	Value (MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)	0.3132 ratio	Standard Deviation 0.08899
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)	0.3549 ratio	Standard Deviation 0.1351
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)	0.3153 ratio	Standard Deviation 0.112

Secondary

Pharmacokinetics Parameters of Metabolite : Parent on Day 7---Cmax

To determine Cmax ratio of metabolite to that of the parent compound on Day 7

Time frame: Day 7

Arm	Measure	Value (MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 7---Cmax	0.2657 ratio	Standard Deviation 0.0782
Ticagrelor 60mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 7---Cmax	0.3082 ratio	Standard Deviation 0.1223
Ticagrelor 90mg	Pharmacokinetics Parameters of Metabolite : Parent on Day 7---Cmax	0.2646 ratio	Standard Deviation 0.06758

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 1(1)

The pharmacokinetics parameters of Ticagrelor on Day 1---Cmax

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(1)	464.0 ng/mL	Geometric Coefficient of Variation 38.02
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(1)	413.9 ng/mL	Geometric Coefficient of Variation 34.14
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(1)	822.1 ng/mL	Geometric Coefficient of Variation 37.39

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 1(2)

The pharmacokinetics parameters of Ticagrelor on Day 1---AUC(0-inf), AUC(0-12h) and AUC(0-t).

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-t)	3102 h*ng/mL	Geometric Coefficient of Variation 49.79
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-inf)	3220 h*ng/mL	Geometric Coefficient of Variation 51.42
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-12h)	2114 h*ng/mL	Geometric Coefficient of Variation 41.97
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-t)	3533 h*ng/mL	Geometric Coefficient of Variation 31.68
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-inf)	3633 h*ng/mL	Geometric Coefficient of Variation 32.46
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-12h)	2313 h*ng/mL	Geometric Coefficient of Variation 30.1
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-inf)	6234 h*ng/mL	Geometric Coefficient of Variation 53.84
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-12h)	3983 h*ng/mL	Geometric Coefficient of Variation 41.93
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(2)	AUC(0-t)	6017 h*ng/mL	Geometric Coefficient of Variation 51.71

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 1(3)

The pharmacokinetics parameter of ticagrelor on Day 1---tmax and t1/2

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1

Arm	Measure	Group	Value (MEDIAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	tmax	2.00 hour	Full Range 38.02
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	t½	10.07 hour	Full Range 51.42
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	tmax	3.00 hour	Full Range 34.14
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	t½	9.008 hour	Full Range 32.46
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	t½	9.802 hour	Full Range 53.84
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 1(3)	tmax	2.00 hour	Full Range 37.39

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 7(1)

Pharmacokinetics parameters of Ticagrelor on Day 7---Cmax

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(1)	616.0 ng/mL	Geometric Coefficient of Variation 37.09
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(1)	689.4 ng/mL	Geometric Coefficient of Variation 33.64
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(1)	1273 ng/mL	Geometric Coefficient of Variation 43

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 7(2)

The pharmacokinetics parameters of ticagrelor on Day 7---tmax

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (MEDIAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(2)	2.00 hour	Full Range 37.09
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(2)	2.00 hour	Full Range 33.64
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(2)	2.00 hour	Full Range 43

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 7(3)

Pharmacokinetics parameters of Ticagrelor on Day 7---AUC(0-12h)

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(3)	3882 h*ng/mL	Geometric Coefficient of Variation 41.67
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(3)	4351 h*ng/mL	Geometric Coefficient of Variation 36.74
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(3)	8206 h*ng/mL	Geometric Coefficient of Variation 50.92

Secondary

Pharmacokinetics Parameters of Ticagrelor on Day 7(4)

Pharmacokinetics parameters of Ticagrelor on Day 7---Accumulation ratio(ratio of Day 7 AUC(0-12h) to Day 1 AUC(0-12h))

Time frame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Ticagrelor 45mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(4)	1.837 ratio	Geometric Coefficient of Variation 23.57
Ticagrelor 60mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(4)	1.882 ratio	Geometric Coefficient of Variation 20.72
Ticagrelor 90mg	Pharmacokinetics Parameters of Ticagrelor on Day 7(4)	2.060 ratio	Geometric Coefficient of Variation 22.84

Secondary

Safety---All Allowed Concomitant Medications During Study Treatment

The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA. Safety will be assessed by: • Concomitant medications

Time frame: All allowed concomitant medications during study treatment(up to 2-5 days after last dose), includes medications that began prior to randomization but were ongoing after randomization.