A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin

Coronary Artery Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528411
• Other study ID #: D5130C00048
• Status: Completed
• Phase: Phase 2
• First received: September 10, 2007
• Last updated: January 12, 2012
• Start date: October 2007
• Est. completion date: March 2009

Study information

• Verified date: January 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Ticagrelor Tablets
Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)
• Clopidogrel (over encapsulated) capsule
Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)
• Aspirin Tablets
Oral, 75 mg to 100 mg once daily. Aspirin obtained locally by the investigator, according to local practice. The dose remained constant throughout the study.

Locations

Country	Name	City	State
United Kingdom	Research Site	Sheffield
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Houston	Texas
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Towson	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose	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.	At 2 hours after first dose of study drug	No
Primary	Slope of Extent IPA Offset Curve 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.	4 to 72 Hours after last dose of study drug	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose	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.	0.5 hours after first dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose	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.	1 hour after first dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose	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.	4 hours after first dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose	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.	8 hours after first dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose	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.	24 hours after first dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose	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.	0 hour before last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose	IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference for baseline versus post baseline value relative to baseline value. 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.	2 hours after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose	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.	4 hours after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose	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.	8 hours after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose	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.	24 hours after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose	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.	48 hours after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose	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.	72 hours after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose	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.	120 hours - Day 5 after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 168 Hours - Day 7 After Last Dose	IPA(%)=(PAb-PAt)/PAb*100. The unit % is the percentage of difference of 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.	168 hours - Day 7 after last dose	No
Secondary	Final Extent IPA Induced by 20 µM ADP at 240 Hours - Day 10 After Last Dose	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.	240 hours - Day 10 after last dose	No
Secondary	Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)	FEV1 is measured by Spirometry, the unit is Liter.	Baseline	Yes
Secondary	Cardiopulmonary Parameters at Post 6-week Treatment: FEV1	FEV1 is measured by Spirometry, the unit is Liter.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)	FVC is measured by Spirometry, the unit is Liter.	Baseline	Yes
Secondary	Cardiopulmonary Parameters at Post 6-week Treatment: FVC	FVC is measured by Spirometry, the unit is Liter.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)	FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.	Baseline	Yes
Secondary	Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio	FEV1/FVC Ratio is measured by Spirometry, the unit is Ratio.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)	FEF25-75 is measured by Spirometry, the unit is Liter/Second.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75	FEF25-75 is measured by Spirometry, the unit is Liter/Second.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)	FRC is measured by Body Box Plethysmography, the unit is Liter.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: FRC	FRC is measured by Body Box Plethysmography, the unit is Liter.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)	TLC is measured by Body Box Plethysmography, the unit is Liter.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: TLC	TLC is measured by Body Box Plethysmography, the unit is Liter.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Residual Volume (RV)	RV is measured by Body Box Plethysmography, the unit is Liter.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: RV	RV is measured by Body Box Plethysmography, the unit is Liter.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)	VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: VE	VE is measured by Spirometry and Body Box Plethysmography, the unit is Liter/Minute	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)	RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: RR	RR is measured by Spirometry and Body Box Plethysmography, the unit is Breaths/Minute.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)	VT is measured by Body Box Plethysmography, the unit is Liter/Minute.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: VT	VT is measured by Body Box Plethysmography, the unit is Liter/Minute.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)	DLCOSB is measured by Body Box Plethysmography, the unit is Percent.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB	DLCOSB is measured by Body Box Plethysmography, the unit is Percent.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)	EF is measured by Echocardiogram, the unit is Percent. The ejection fraction is defined by: (LV diastolic volume - LV systolic volume)/LV diastolic volume. The unit % is the percentage change of left ventricular diastolic versus systolic volume relative to the diastolic volume. LV is the left ventricle.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: EF	EF is measured by Echocardiogram, the unit is Percent. The ejection fraction is defined by: (LV diastolic volume - LV systolic volume)/LV diastolic volume. The unit % is the percentage change of left ventricular diastolic versus systolic volume relative to the diastolic volume. LV is the left ventricle.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)	NT-proBNP is measured by clinical lab, the unit is pg/mL.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP	NT-proBNP is measured by clinical lab, the unit is pg/mL.	6-week post treatment	Yes
Secondary	Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2)	SpO2 is measured by pulse oximetry, the unit is Percent. The unit % is the percentage of oxygen attached hemoglobin relative to the total hemoglobin.	Baseline	Yes
Secondary	Cardiopulmonary Parameters Post 6-week Treatment: SpO2	SpO2 is measured by pulse oximetry, the unit is Percent. The unit % is the percentage of oxygen attached hemoglobin relative to the total hemoglobin.	6-week post treatment	Yes

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