A Study to Investigate the Interaction Between ACT-246475 and Clopidogrel, Prasugrel, and Ticagrelor in Healthy Subjects

Viatris Innovation GmbH

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: ACT-246475; Drug: Clopidogrel; Drug: Ticagrelor; Drug: Placebo; Drug: Prasugrel

Study type: Interventional

Funder types: Industry

Identifiers

NCT03430661

ID-076-103

Details and patient eligibility

About

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

Enrollment: 77 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Main 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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77 participants in 9 patient groups

Part A: Group 1

Experimental group

Description:

Clopidogrel will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax

Treatment:

Drug: Placebo

Drug: Clopidogrel

Drug: ACT-246475

Part A: Group 2

Experimental group

Description:

Clopidogrel will be administered 12 h after ACT-246475 or placebo

Treatment:

Drug: Placebo

Drug: Clopidogrel

Drug: ACT-246475

Part A: Group 3

Experimental group

Description:

Any time interval up to 24 h between the administration of ACT-246475 or placebo and clopidogrel may be studied

Treatment:

Drug: Placebo

Drug: Clopidogrel

Drug: ACT-246475

Part B: Group 1

Experimental group

Description:

Prasugrel will be administered 12 h after ACT-246475 or placebo

Treatment:

Drug: Prasugrel

Drug: Placebo

Drug: ACT-246475

Part B: Group 2

Experimental group

Description:

Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied

Treatment:

Drug: Prasugrel

Drug: Placebo

Drug: ACT-246475

Part B: Group 3

Experimental group

Description:

Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied

Treatment:

Drug: Prasugrel

Drug: Placebo

Drug: ACT-246475

Part C: Group 1

Experimental group

Description:

Ticagrelor will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax

Treatment:

Drug: Placebo

Drug: Ticagrelor

Drug: ACT-246475

Part C: Group 2

Experimental group

Description:

Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied

Treatment:

Drug: Placebo

Drug: Ticagrelor

Drug: ACT-246475

Part C: Group 3

Experimental group

Description:

Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied

Treatment:

Drug: Placebo

Drug: Ticagrelor

Drug: ACT-246475