A Multi-centre Randomised, Double-blind, Double-dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of Ticagrelor Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease (CAD)
Overview
- Phase
- Phase 2
- Intervention
- Aspirin Tablets
- Conditions
- Coronary Artery Disease
- Sponsor
- AstraZeneca
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
The purpose of this study is to see how Ticagrelor, a new oral reversible anti-platelet medication, affects platelets. Anti-platelet agents are medications that block the formation of blood clots by preventing the clumping of platelets. Blood clots prevent us from bleeding, but when they form inside the arteries their formation is linked to a risk of medical problems such as heart attack and stroke. This study investigated how long it takes for Ticagrelor to begin working and how long it takes for it to stop working after the last dose of drug. Ticagrelor will be compared to clopidogrel, an established anti-platelet treatment for preventing blood clots, and placebo plus Aspirin.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Documented stable Coronary Artery Disease (stable angina, previous MI history, previous history of revascularization);
- •Females of child bearing potential must have a negative pregnancy test prior to receiving study drug and be willing to use a hormonal contraceptive in addition to double barrier contraception
Exclusion Criteria
- •History of Acute Coronary Syndromes within 12 months of screening or need for revascularization (angioplasty or Coronary Artery Bypass Graft (CABG))
- •History of liver or kidney disease
- •Have increased bleeding risk, eg, recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count, recent major trauma
- •History of intolerance or allergy to Aspirin or clopidogrel
Arms & Interventions
1
Aspirin + Placebo
Intervention: Aspirin Tablets
2
Aspirin + clopidogrel
Intervention: Clopidogrel (over encapsulated) capsule
2
Aspirin + clopidogrel
Intervention: Aspirin Tablets
3
Aspirin + Ticagrelor
Intervention: Ticagrelor Tablets
3
Aspirin + Ticagrelor
Intervention: Aspirin Tablets
Outcomes
Primary Outcomes
Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose
Time Frame: At 2 hours after first dose of study drug
IPA(%)=(PAb-PAt)/PAb\*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition.
Slope of Extent IPA Offset Curve 4 to 72 Hours After Last Dose of Study Drug
Time Frame: 4 to 72 Hours after last dose of study drug
IPA(%)=(PAb-PAt)/PAb\*100.The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value of platelet aggregation. PA (platelet aggregation) is measured by LTA (Light Transmittance Aggregometry). PAb is the response at baseline (last measurement before study drug) and PAt is a response at post-treatment. IPA=0% means no PA inhibition and 100% means 100% PA inhibition. The unit for the slope of IPA curve is percent/hour.
Secondary Outcomes
- Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose(0.5 hours after first dose)
- Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose(1 hour after first dose)
- Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose(4 hours after first dose)
- Cardiopulmonary Parameters at Post 6-week Treatment: FEV1(6-week post treatment)
- Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose(8 hours after first dose)
- Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose(24 hours after first dose)
- Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose(0 hour before last dose)
- Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose(2 hours after last dose)
- Cardiopulmonary Parameters Post 6-week Treatment: FRC(6-week post treatment)
- Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose(4 hours after last dose)
- Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose(8 hours after last dose)
- Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose(24 hours after last dose)
- Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose(48 hours after last dose)
- Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose(72 hours after last dose)
- Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose(120 hours - Day 5 after last dose)
- Final Extent IPA Induced by 20 µM ADP at 168 Hours - Day 7 After Last Dose(168 hours - Day 7 after last dose)
- Final Extent IPA Induced by 20 µM ADP at 240 Hours - Day 10 After Last Dose(240 hours - Day 10 after last dose)
- Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)(Baseline)
- Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)(Baseline)
- Cardiopulmonary Parameters at Post 6-week Treatment: FVC(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)(Baseline)
- Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)(Baseline)
- Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: TLC(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Residual Volume (RV)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: RV(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: VE(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: RR(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: VT(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: EF(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP(6-week post treatment)
- Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2)(Baseline)
- Cardiopulmonary Parameters Post 6-week Treatment: SpO2(6-week post treatment)