Ticagrelor China Pharmacokinetic/Pharmacodynamic Study

Stable Coronary Heart Disease (CHD) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02064985
• Other study ID #: D5130C00086
• Status: Completed
• Phase: Phase 4
• First received: February 12, 2014
• Last updated: November 27, 2014
• Start date: February 2014
• Est. completion date: November 2014

Study information

• Verified date: November 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Myocardial Ischemia
• Stable Coronary Heart Disease (CHD)

Intervention

Drug:
• Inhibition 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).

Locations

Country	Name	City	State
China	Research Site	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacodynamic	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).; 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)	7 Days	No
Secondary	Pharmacodynamic	To determine the P2Y12 Reaction Units (PRU) (VerifyNow) profiles of single and multiple doses of ticagrelor 45, 60, and 90 mg in Chinese patients with stable coronary heart disease on chronic low dose ASA.; Secondary variable:Time to peak IPA (TIPAmax) and the area-under-the-effect curve (AUEC) will be estimated for ADP-induced final extent IPA.; Inhibition of the P2Y12 receptor at each assessment point after single and multiple doses of ticagrelor as measured by PRU from VerifyNowTM Percent reduction in PRU at each assessment point measured by VerifyNowTM on P2Y12 reaction units , represented as percentage change form baseline (pre-treatment) after single and multiple doses of ticagrelor.	7days	No
Secondary	Pharmacokinetics	To determine the PK of ticagrelor and AR-C124910XX (active metabolite). Day 1 PK variables: Cmax, tmax, AUC(0-12h), AUC(0-t), AUC and t1/2 of ticagrelor and AR-C124910XX, metabolite:parent Cmax and AUC ratios. Day 7 PK variables: Cmax, tmax, and AUC(0-12h) of ticagrelor and AR-C124910XX, metabolite:parent Cmax and AUC(0-12h) ratios and accumulation ratio (AR) for ticagrelor and AR-C124910XX.	7days	No
Secondary	Safety	To assess 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], pulse); Physical examination; Haematology, Clinical Chemistry, and Urinalysis; Assessment of adverse events and concomitant medications	7days	Yes