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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACT-246475; Drug: Clopidogrel; Drug: Placebo; Drug: Prasugrel; Drug: Ticagrelor

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Biotrial Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Group 1; Clopidogrel will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Clopidogrel; Tablet for oral administration (300 or 600 mg); Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
Experimental: Part A: Group 2; Clopidogrel will be administered 12 h after ACT-246475 or placebo	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Clopidogrel; Tablet for oral administration (300 or 600 mg); Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
Experimental: Part A: Group 3; Any time interval up to 24 h between the administration of ACT-246475 or placebo and clopidogrel may be studied	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Clopidogrel; Tablet for oral administration (300 or 600 mg); Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
Experimental: Part B: Group 1; Prasugrel will be administered 12 h after ACT-246475 or placebo	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution; Drug: Prasugrel; Tablet for oral administration (60 mg)
Experimental: Part B: Group 2; Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution; Drug: Prasugrel; Tablet for oral administration (60 mg)
Experimental: Part B: Group 3; Any time interval up to 24 h between the administration of ACT-246475 or placebo and prasugrel may be studied	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution; Drug: Prasugrel; Tablet for oral administration (60 mg)
Experimental: Part C: Group 1; Ticagrelor will be administered 0.5 h after ACT-246475 or placebo, i.e., at the time of tmax	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution; Drug: Ticagrelor; Tablet for oral administration (180 mg)
Experimental: Part C: Group 2; Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution; Drug: Ticagrelor; Tablet for oral administration (180 mg)
Experimental: Part C: Group 3; Any time interval up to 24 h between the administration of ACT-246475 or placebo and ticagrelor may be studied	Drug: ACT-246475; Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection; Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution; Drug: Ticagrelor; Tablet for oral administration (180 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): May 20, 2019
• Study Completion (Actual): May 29, 2019

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: ID-076-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No