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Completed

NCT Number: NCT02064985

Ticagrelor China Pharmacokinetic/Pharmacodynamic Study

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

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Key information

Conditions

Stable Coronary Heart Disease (CHD)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Research Site

Beijing, China

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Provision of signed and dated written informed consent prior to any study specific procedures.
  • Female or male Chinese (as defined by Chinese Regulatory) patients aged 18 years or older with suitable veins for cannulations or repeated venipunctures.
  • 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.

  • Female patients without pregnant potential

Exclusion criteria

  • Any indication for oral anticoagulant or dual antiplatelet treatment and chronic ASA with doses greater than 100 mg/day.
  • 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.
  • Increased bleeding risk.
  • Contraindication or other reason that ASA or ticagrelor should not be administered
  • Patients that are scheduled for revascularization (eg, PCI, CABG) during the study period

Treatment and study plan

Inhibition of Platelet Aggregation by "Brilinta"(Ticagrelor)

Drug

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).

Other names: "Brilinta"(Ticagrelor)

Primary outcomes

  1. IPA on Day 1

    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

    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).

  2. IPA 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

    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 outcomes

  1. Percent Change From Baseline in PRU on Day 1

    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

    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.

  2. Pharmacokinetics Parameters of Ticagrelor on Day 7(1)

    Time frame: 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

  3. Safety---Vital Signs Over Time---Blood Pressure

    Time frame: 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])

  4. 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

    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.

  5. TIPA(Max)---Day 1

    Time frame: Day 1

    The time to peak IPA (TIPAmax) was estimated for ADP-induced final extent IPA.

  6. TIPA(Max)---Day 7

    Time frame: Day 7

    The time to peak IPA (TIPAmax) was estimated for ADP-induced final extent IPA.

  7. AUEC(Final Extent) on Day 1

    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

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

  8. AUEC(Final Extent) on Day 7

    Time frame: 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.

  9. Pharmacokinetics Parameters of Ticagrelor on Day 1(3)

    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

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

  10. Pharmacokinetics Parameters of Ticagrelor on Day 1(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

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

  11. Pharmacokinetics Parameters of Ticagrelor on Day 7(2)

    Time frame: 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

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

    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

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

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

    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

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

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

    Time frame: 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

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

    Time frame: 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

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

    Time frame: Day 1

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

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

    Time frame: Day 7

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

  18. Safety---Physical Examination, Summary of Abnormalities

    Time frame: 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

  19. Safety---Hematology Laboratory Variables Over Time---hematocrit

    Time frame: 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

  20. Safety---All Allowed Concomitant Medications During Study Treatment

    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.

    The safety of ticagrelor in Chinese patients with stable coronary heart disease on chronic low dose ASA.

    Safety will be assessed by:

    • Concomitant medications

  21. Safety---Causally Related Adverse Events by System Organ Class and Preferred Term

    Time frame: 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

  22. Pharmacokinetics Parameters of Ticagrelor on Day 1(1)

    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

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

  23. Pharmacokinetics Parameters of Ticagrelor on Day 7(3)

    Time frame: 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)

  24. Pharmacokinetics Parameters of Ticagrelor on Day 7(4)

    Time frame: 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))

  25. Safety---Vital Signs Over Time---Height

    Time frame: 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)

  26. Safety---Vital Signs Over Time---Weight

    Time frame: 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)

  27. Safety---Vital Signs Over Time---Pulse Rate

    Time frame: 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)

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

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

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

    Time frame: 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)

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

    Time frame: 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))

  31. Safety---Hematology Laboratory Variables Over Time---Erythrocytes

    Time frame: 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

  32. Safety---Hematology Laboratory Variables Over Time---Hemoglobin

    Time frame: 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

  33. Safety---Hematology Laboratory Variables Over Time---Leukocytes

    Time frame: 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

  34. Safety---Hematology Laboratory Variables Over Time---Platelets

    Time frame: 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

  35. Safety---Clinical Chemistry Variables Over Time---Glucose

    Time frame: 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

  36. Safety---Clinical Chemistry Variables Over Time---Alanine Aminotransferase

    Time frame: 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

  37. Safety---Clinical Chemistry Variables Over Time---Aspartate Aminotransferase

    Time frame: 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

  38. Safety---Clinical Chemistry Variables Over Time---Alkaline Phosphatase

    Time frame: 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

  39. Safety---Clinical Chemistry Variables Over Time---Creatinine

    Time frame: 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

  40. Safety---Clinical Chemistry Variables Over Time---Total Bilirubin

    Time frame: 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

  41. Safety---Clinical Chemistry Variables Over Time---Sodium

    Time frame: 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

  42. Safety---Clinical Chemistry Variables Over Time---Potassium

    Time frame: 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

  43. Safety---Clinical Chemistry Variables Over Time---Chloride

    Time frame: 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

  44. Safety---Clinical Chemistry Variables Over Time---Phosphate

    Time frame: 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

  45. Safety---Clinical Chemistry Variables Over Time---Albumin

    Time frame: 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

  46. Safety---Clinical Chemistry Variables Over Time---Protein

    Time frame: 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

  47. Safety---Clinical Chemistry Variables Over Time---Blood Urea Nitrogen

    Time frame: 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

  48. Safety---Clinical Chemistry Variables Over Time---Bicarbonate

    Time frame: 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

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

    Time frame: Day 1

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

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

    Time frame: Day 7

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

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2014
Study completion
2014
First posted
Feb 17, 2014
Registry last updated
May 11, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.