Clinical trial NCT03430661: A Study to Investigate the Interaction Between ACT-246475 and Clopidogrel, Prasugrel, and Ticagrelor in Healthy Subjects
Official title: Single-center, Double-blind (ACT-246475), Open-label (Clopidogrel, Prasugrel, and Ticagrelor), Placebo-controlled, Randomized, Two-way Crossover Study to Investigate the Pharmacodynamics, Safety, and Tolerability of a Single Oral Dose of Clopidogrel or, Prasugrel, or Ticagrelor When Administered After a Single Subcutaneous Dose of the P2Y12 Antagonist ACT-246475 in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-02-13
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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


Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: From baseline up to 48 hours
measure: 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.
timeFrame: From baseline up to 48 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Newark
country: United States
facility: Biotrial Inc
state: New Jersey
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Schilling U, Dingemanse J, Dobrow M, Baumann M, Riederer MA, Juif PE, Ufer M. Insights from In Vitro and Clinical Data to Guide Transition from the Novel P2Y12 Antagonist Selatogrel to Clopidogrel, Prasugrel, and Ticagrelor. Thromb Haemost. 2021 Jun;121(6):755-766. doi: 10.1055/s-0040-1721773. Epub 2021 Jan 7.