Ticagrelor China Pharmacokinetic/Pharmacodynamic Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02064985
First received: February 12, 2014
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Stable Coronary Heart Disease (CHD)
Drug: Inhibition of Platelet Aggregation by "Brilinta"(Ticagrelor)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Pharmacodynamic [ Time Frame: 7 Days ] [ Designated as safety issue: No ]

    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)



Secondary Outcome Measures:
  • Pharmacodynamic [ Time Frame: 7days ] [ Designated as safety issue: No ]

    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.


  • Pharmacokinetics [ Time Frame: 7days ] [ Designated as safety issue: No ]
    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.

  • Safety [ Time Frame: 7days ] [ Designated as safety issue: Yes ]

    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


Estimated Enrollment: 36
Study Start Date: February 2014
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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).
Other Name: "Brilinta"(Ticagrelor)
Experimental: 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.
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).
Other Name: "Brilinta"(Ticagrelor)
Experimental: 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.
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).
Other Name: "Brilinta"(Ticagrelor)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02064985

Contacts
Contact: Anders Himmelmann 46317762282 ClinicalTrialTransparency@astrazeneca.com

Locations
China
Research Site Recruiting
Beijing, China
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Haiyan Li, PhD The 3rd Hospital of Peking University
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02064985     History of Changes
Other Study ID Numbers: D5130C00086
Study First Received: February 12, 2014
Last Updated: August 20, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 14, 2014