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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- IPA on Day 1
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Inhibition of Platelet Aggregation by "Brilinta"(Ticagrelor) (Drug)
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.
干预措施: Inhibition of Platelet Aggregation by "Brilinta"(Ticagrelor) (Drug)
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.
干预措施: Inhibition of Platelet Aggregation by "Brilinta"(Ticagrelor) (Drug)
结局指标
主要结局
IPA on Day 1
时间窗: 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
时间窗: 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).
次要结局
- 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)
- 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)
- Safety---Vital Signs Over Time---Blood Pressure(Baseline, Day 1 to Day 7 and 2 to 5 days after last dose)
- 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)
- TIPA(Max)---Day 1(Day 1)
- 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)
- Safety---Hematology Laboratory Variables Over Time---Erythrocytes(2 to 5 days after last dose)
- TIPA(Max)---Day 7(Day 7)
- 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)
- 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)
- 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)
- Safety---Hematology Laboratory Variables Over Time---hematocrit(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Protein(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Blood Urea Nitrogen(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Bicarbonate(2 to 5 days after last dose)
- 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)
- Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax(Day 1)
- 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)
- 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 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)
- Safety---Physical Examination, Summary of Abnormalities(2 to 5 days after last dose)
- 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).)
- 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(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 Metabolite : Parent on Day 7---Cmax(Day 7)
- 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.)
- 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(4)(Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7)
- Safety---Vital Signs Over Time---Height(Baseline)
- Safety---Vital Signs Over Time---Weight(Baseline)
- Safety---Vital Signs Over Time---Pulse Rate(Baseline, Day 1 to Day 7 and 2 to 5 days after last dose)
- 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 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(3)(Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7)
- Safety---Hematology Laboratory Variables Over Time---Hemoglobin(2 to 5 days after last dose)
- Safety---Hematology Laboratory Variables Over Time---Leukocytes(2 to 5 days after last dose)
- Safety---Hematology Laboratory Variables Over Time---Platelets(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Glucose(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Alanine Aminotransferase(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Aspartate Aminotransferase(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Alkaline Phosphatase(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Creatinine(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Total Bilirubin(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Sodium(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Potassium(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Chloride(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Phosphate(2 to 5 days after last dose)
- Safety---Clinical Chemistry Variables Over Time---Albumin(2 to 5 days after last dose)
- Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)(Day 1)
- Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)(Day 7)