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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03430661
• Other study ID #: ID-076-103
• Status: Completed
• Phase: Phase 1
• Start date: January 24, 2018
• Est. completion date: May 29, 2019

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: May 29, 2019
• Est. primary completion date: May 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ACT-246475
Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection
• Clopidogrel
Tablet for oral administration (300 or 600 mg)
• Prasugrel
Tablet for oral administration (60 mg)
• Placebo
Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
• Ticagrelor
Tablet for oral administration (180 mg)

Locations

Country	Name	City	State
United States	Biotrial Inc	Newark	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	- IPA%[MPA] will be calculated as mean change in percentage from baseline for each time point.	From baseline up to 48 hours
Primary	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.	- 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).	From baseline up to 48 hours