Clinical trial NCT02064985: Ticagrelor China Pharmacokinetic/Pharmacodynamic Study
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Stable Coronary Heart Disease (CHD)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-02-17
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: IPA on Day 1
timeFrame: 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
measure: IPA on Day 7
timeFrame: Baseline and at 0 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours after dose intake on Day 7
Secondary outcomes:
measure: Percent Change From Baseline in PRU on Day 1
timeFrame: 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
measure: Pharmacokinetics Parameters of Ticagrelor on Day 7(1)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Safety---Vital Signs Over Time---Blood Pressure
timeFrame: Baseline, Day 1 to Day 7 and 2 to 5 days after last dose
measure: Percent Change From Baseline in PRU on Day 7
timeFrame: Baseline and at 0 hour, 0.5 hour, 1 hour, 2 hours, 3 hours, 6 hours, 12 hours after dose intake on Day 7
measure: TIPA(Max)---Day 1
timeFrame: Day 1
measure: TIPA(Max)---Day 7
timeFrame: Day 7
measure: AUEC(Final Extent) on Day 1
timeFrame: IPA was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: AUEC(Final Extent) on Day 7
timeFrame: IPA was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Pharmacokinetics Parameters of Ticagrelor on Day 1(3)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: Pharmacokinetics Parameters of Ticagrelor on Day 1(2)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: Pharmacokinetics Parameters of Ticagrelor on Day 7(2)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(1)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(3)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(1)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(4)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Pharmacokinetics Parameters of Metabolite : Parent on Day 1--Cmax
timeFrame: Day 1
measure: Pharmacokinetics Parameters of Metabolite : Parent on Day 7---Cmax
timeFrame: Day 7
measure: Safety---Physical Examination, Summary of Abnormalities
timeFrame: 2 to 5 days after last dose
measure: Safety---Hematology Laboratory Variables Over Time---hematocrit
timeFrame: 2 to 5 days after last dose
measure: Safety---All Allowed Concomitant Medications During Study Treatment
timeFrame: 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.
measure: Safety---Causally Related Adverse Events by System Organ Class and Preferred Term
timeFrame: 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).
measure: Pharmacokinetics Parameters of Ticagrelor on Day 1(1)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: Pharmacokinetics Parameters of Ticagrelor on Day 7(3)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Pharmacokinetics Parameters of Ticagrelor on Day 7(4)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Safety---Vital Signs Over Time---Height
timeFrame: Baseline
measure: Safety---Vital Signs Over Time---Weight
timeFrame: Baseline
measure: Safety---Vital Signs Over Time---Pulse Rate
timeFrame: Baseline, Day 1 to Day 7 and 2 to 5 days after last dose
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 1(2)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6, 12, 24, 36, and 48 hours post dose on Day 1
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(2)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Pharmacokinetics Parameters of Metabolite (AR-C124910XX) on Day 7(3)
timeFrame: Plasma concentration was measured at Pre-dose, 0.5, 1, 2, 3, 6 and 12 hours post dose on Day 7
measure: Safety---Hematology Laboratory Variables Over Time---Erythrocytes
timeFrame: 2 to 5 days after last dose
measure: Safety---Hematology Laboratory Variables Over Time---Hemoglobin
timeFrame: 2 to 5 days after last dose
measure: Safety---Hematology Laboratory Variables Over Time---Leukocytes
timeFrame: 2 to 5 days after last dose
measure: Safety---Hematology Laboratory Variables Over Time---Platelets
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Glucose
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Alanine Aminotransferase
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Aspartate Aminotransferase
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Alkaline Phosphatase
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Creatinine
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Total Bilirubin
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Sodium
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Potassium
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Chloride
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Phosphate
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Albumin
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Protein
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Blood Urea Nitrogen
timeFrame: 2 to 5 days after last dose
measure: Safety---Clinical Chemistry Variables Over Time---Bicarbonate
timeFrame: 2 to 5 days after last dose
measure: Pharmacokinetics Parameters of Metabolite : Parent on Day 1--AUC(0-inf)
timeFrame: Day 1
measure: Pharmacokinetics Parameters of Metabolite : Parent on Day 7---AUC(0-12h)
timeFrame: Day 7
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
Study officials:
affiliation: The 3rd Hospital of Peking University
name: Haiyan Li, PhD
role: PRINCIPAL_INVESTIGATOR
References: