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

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)”

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.

Intervention(s) in this Clinical Trial

• Drug: Ticagrelor Tablets
  • Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)
• Drug: Clopidogrel (over encapsulated) capsule
  • Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)
• Drug: 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.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Aspirin + Placebo
• Active Comparator: 2
  • Aspirin + clopidogrel
• Experimental: 3
  • Aspirin + Ticagrelor

Primary Measures

• 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
    Safety Issue?: No
• 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
    Safety Issue?: No

Secondary Measures

• Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose
  • Time Frame: 0.5 hours after first dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose
  • Time Frame: 1 hour after first dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose
  • Time Frame: 4 hours after first dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose
  • Time Frame: 8 hours after first dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose
  • Time Frame: 24 hours after first dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose
  • Time Frame: 0 hour before last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose
  • Time Frame: 2 hours after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose
  • Time Frame: 4 hours after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose
  • Time Frame: 8 hours after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose
  • Time Frame: 24 hours after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose
  • Time Frame: 48 hours after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose
  • Time Frame: 72 hours after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose
  • Time Frame: 120 hours - Day 5 after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 168 Hours - Day 7 After Last Dose
  • Time Frame: 168 hours - Day 7 after last dose
    Safety Issue?: No
• Final Extent IPA Induced by 20 µM ADP at 240 Hours - Day 10 After Last Dose
  • Time Frame: 240 hours - Day 10 after last dose
    Safety Issue?: No
• Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Post 6-week Treatment: FEV1
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Post 6-week Treatment: FVC
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: FRC
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: TLC
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Residual Volume (RV)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: RV
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: VE
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: RR
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: VT
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: EF
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes
• Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2)
  • Time Frame: Baseline
    Safety Issue?: Yes
• Cardiopulmonary Parameters Post 6-week Treatment: SpO2
  • Time Frame: 6-week post treatment
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: AstraZeneca Industry

Overall Clinical Trial Officials and Contacts

Philip Sager, MD Study Director AstraZeneca  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00528411

Study ID Number: D5130C00048

ClinicalTrials.gov Identifier: NCT00528411

Health Authority: United States: Food and Drug Administration