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

Completed

Phase 2 Results

Trial Description

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.

Conditions

Interventions

  • Clopidogrel (Plavix®)Drug
    Other Names: Plavix
    Intervention Desc: 75 mg once daily oral dosage
    ARM 1: Kind: Experimental
    Label: 2
    Description: Aspirin + clopidogrel
  • Aspirin Drug
    Other Names: Aspirin at bedtime
    Intervention Desc: 325 mg oral tablet once daily dose
    ARM 1: Kind: Experimental
    Label: 1
    Description: Aspirin therapy + Placebo
    ARM 2: Kind: Experimental
    Label: 2
    Description: Aspirin + clopidogrel
    ARM 3: Kind: Experimental
    Label: 3
    Description: Aspirin + AZD6140
  • AZD6140 Drug
    Intervention Desc: oral tablet
    ARM 1: Kind: Experimental
    Label: 3
    Description: Aspirin + AZD6140
  • Ticagrelor Tablets Drug
    Intervention Desc: Oral, 90 mg; 180 mg loading dose followed by 90 mg twice daily (BD)
    ARM 1: Kind: Experimental
    Label: 3
    Description: Aspirin + Ticagrelor
  • Clopidogrel (over encapsulated) capsule Drug
    Other Names: Plavix; Clopidogrel Bisulfate
    Intervention Desc: Oral 75 mg; 600 mg loading dose followed by 75 mg once daily (ODD)
    ARM 1: Kind: Experimental
    Label: 2
    Description: Aspirin + clopidogrel
  • Aspirin Tablets Drug
    Other Names: ASA
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: 1
    Description: Aspirin + Placebo
    ARM 2: Kind: Experimental
    Label: 2
    Description: Aspirin + clopidogrel
    ARM 3: Kind: Experimental
    Label: 3
    Description: Aspirin + Ticagrelor

Trial Design

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

Patient Involvement

Patients will be randomized to one of 3 arms: Active Comparator arm (1) will get Aspirin 325 mg + Placebo; Active Comparator arm (2) will get Aspirin 325 mg + clopidogrel 75 mg ; and Experimental arm (3) Aspirin 325 mg + AZD6140 . All given once daily. Primary outcome is assessed 2 hours after first and last doses. Secondary outcomes are assessed at each visit.

Outcomes

Type Measure Time Frame Safety Issue
Primary To determine the onset and offset of antiplatelet effect of AZD6140 compared to clopidogrel by evaluation of the percentage of inhibition of platelet aggregation by light transmission aggregometry (LTA) and by evaluation of the difference in slope of inhibition of platelet aggregation effect curve by LTA.
Secondary To evaluate the pharmacokinetic/pharmacodynamic relationship of AZD6140 and its active metabolite; to determine the effect on platelet aggregation of AZD6140 compared to clopidogrel; to assess the overall safety and tolerability of AZD6140 compared to clopidogrel and placebo.
Primary To determine the onset and offset of antiplatelet effect of AZD6140 compared to clopidogrel by evaluation of the % IPA by LTA and by evaluation of the difference in slope of IPA effect curve by LTA Assessed 2 hrs post 1st dose of drug and after the last dose of drug No
Secondary To evaluate the PK/PD relationship of AZD6140 and its active metabolite; to determine the effect on platelet aggregation of AZD6140 compared to clopidogrel; to assess the overall safety and tolerability of AZD6140 compared to clopidogrel and placebo Assessed at each visit No
Primary Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose 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 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 0.5 hours after first dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose 1 hour after first dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose 4 hours after first dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose 8 hours after first dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose 24 hours after first dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose 0 hour before last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose 2 hours after last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose 4 hours after last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose 8 hours after last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose 24 hours after last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose 48 hours after last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose 72 hours after last dose No
Secondary Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose 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 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 240 hours - Day 10 after last dose No
Secondary Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1) Baseline Yes
Secondary Cardiopulmonary Parameters at Post 6-week Treatment: FEV1 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC) Baseline Yes
Secondary Cardiopulmonary Parameters at Post 6-week Treatment: FVC 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) Baseline Yes
Secondary Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: FRC 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: TLC 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Residual Volume (RV) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: RV 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: VE 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: RR 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Tidal Volume (VT) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: VT 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: EF 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP 6-week post treatment Yes
Secondary Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2) Baseline Yes
Secondary Cardiopulmonary Parameters Post 6-week Treatment: SpO2 6-week post treatment Yes

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