A Study to Investigate the Interaction Between ACT-246475 and Clopidogrel, Prasugrel, and Ticagrelor in Healthy Subjects
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT03430661
- Lead Sponsor
- Idorsia Pharmaceuticals Ltd.
- Brief Summary
The primary objective of this study is to assess the pharmacodynamic (PD) effects of clopidogrel, prasugrel, and ticagrelor when administered after a single subcutaneous (s.c.) dose of ACT-246475 in healthy male and female subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 77
Inclusion Criteria
- Signed informed consent
- Healthy male and female subjects aged between 18 and 65 years (inclusive) at screening
- Body mass index of 18.0 to 31.0 kg/m2 (inclusive) at Screening
- Women of childbearing potential must have a negative serum pregnancy test and use reliable birth controls from screening up to at least 30 days after last study treatment administration
- Systolic blood pressure (SBP) 100-140 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 50-90 beats per minute (bpm) (inclusive) at screening
- Healthy on the basis of physical examination, cardiovascular assessments, and laboratory tests
- Maximum (at peak) platelet aggregation ≥ 40% (light transmission aggregometry [LTA]) upon 20 μM adenosine diphosphate (ADP) activation at screening
- Values of closure time tested with the Platelet Function Analyzer (PFA) equipment, for both cartridges of collagen/adrenaline and collagen/ADP below the upper limit of normal range at screening
Main
Exclusion Criteria
- Pregnant or lactating women
- Known hypersensitivity to ACT-246475, clopidogrel, prasugrel, ticagrelor, any of their excipients, or drugs of the same class
- Any contraindication to clopidogrel, prasugrel, or ticagrelor treatment
- Known hypersensitivity or allergy to natural rubber latex
- Platelet count < 120 × 109 L-1 at Screening and Day -1
- Known platelet disorders (e.g., Glanzmann thromboasthenia, von Willebrand disease, platelet release defect)
- Previous treatment with acetylsalicylate, non-steroidal anti-inflammatory drugs, P2Y12 receptor antagonists, or any medication with blood-thinning activity (i.e., injectable or oral anticoagulants) within 3 weeks prior to study treatment administration
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Group 2 Placebo Clopidogrel will be administered 12 h after ACT-246475 or placebo Part B: Group 2 Placebo Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied Part A: Group 2 ACT-246475 Clopidogrel will be administered 12 h after ACT-246475 or placebo Part A: Group 3 ACT-246475 Any time interval up to 24 h between the administration of ACT-246475 or placebo and clopidogrel may be studied Part A: Group 3 Placebo Any time interval up to 24 h between the administration of ACT-246475 or placebo and clopidogrel may be studied Part B: Group 1 Placebo Prasugrel will be administered 12 h after ACT-246475 or placebo Part C: Group 1 Placebo Ticagrelor will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax Part A: Group 1 Placebo Clopidogrel will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax Part B: Group 3 Placebo Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied Part C: Group 3 Placebo Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied Part C: Group 2 Placebo Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied Part A: Group 1 Clopidogrel Clopidogrel will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax Part A: Group 2 Clopidogrel Clopidogrel will be administered 12 h after ACT-246475 or placebo Part A: Group 3 Clopidogrel Any time interval up to 24 h between the administration of ACT-246475 or placebo and clopidogrel may be studied Part B: Group 1 Prasugrel Prasugrel will be administered 12 h after ACT-246475 or placebo Part B: Group 1 ACT-246475 Prasugrel will be administered 12 h after ACT-246475 or placebo Part B: Group 2 ACT-246475 Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied Part B: Group 2 Prasugrel Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied Part B: Group 3 Prasugrel Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied Part C: Group 1 Ticagrelor Ticagrelor will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax Part C: Group 2 Ticagrelor Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied Part C: Group 3 Ticagrelor Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied Part A: Group 1 ACT-246475 Clopidogrel will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax Part B: Group 3 ACT-246475 Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied Part C: Group 1 ACT-246475 Ticagrelor will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax Part C: Group 3 ACT-246475 Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied Part C: Group 2 ACT-246475 Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied
- Primary Outcome Measures
Name Time Method Time-matched comparisons of IPA% (MPA) between treatments (i.e., Treatment A1 vs A2, Treatment B1 vs B2, and treatment C1 vs C2, treatments are defined below) following administration of ACT-246475 and its matching placebo. From baseline up to 48 hours - IPA%\[MPA\] will be calculated as mean change in percentage from baseline for each time point.
Time-matched comparisons of IPA %(PRU) between treatments (i.e., Treatment A1 vs A2, Treatment B1 vs B2, and treatment C1 vs C2) following administration of ACT-246475 and its matching placebo. From baseline up to 48 hours - IPA%\[PRU\] will be calculated as mean change in percentage from baseline for each time point.
Treatment A1: single s.c. dose administration of ACT-246475-matching placebo followed by a single oral dose of clopidogrel (600 mg).
Treatment A2: single s.c. dose administration (16 mg) of ACT-246475 followed by a single oral dose of clopidogrel (300 mg).
Treatment B1: single s.c. dose administration of ACT-246475-matching placebo followed by a single oral dose of prasugrel (60 mg).
Treatment B2: single s.c. dose administration (16 mg) of ACT-246475 followed by a single oral dose of prasugrel (60 mg).
Treatment C1: single s.c. dose administration of ACT-246475-matching placebo followed by a single oral dose of ticagrelor (180 mg).
Treatment B2: single s.c. dose administration (16 mg) of ACT-246475 followed by a single oral dose of ticagrelor (180 mg).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Biotrial Inc
🇺🇸Newark, New Jersey, United States