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

NCT03430661 | Completed Phase 1 FDA Drug

• 1 other identifier: ID-076-103
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (9)

Part A: Group 1

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Clopidogrel; Drug: Placebo

Part A: Group 2

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Clopidogrel; Drug: Placebo

Part A: Group 3

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Clopidogrel; Drug: Placebo

Part B: Group 1

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Prasugrel; Drug: Placebo

Part B: Group 2

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Prasugrel; Drug: Placebo

Part B: Group 3

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Prasugrel; Drug: Placebo

Part C: Group 1

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Placebo; Drug: Ticagrelor

Part C: Group 2

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Placebo; Drug: Ticagrelor

Part C: Group 3

EXPERIMENTAL

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

Drug: ACT-246475; Drug: Placebo; Drug: Ticagrelor

Interventions

ACT-246475 DRUG

Lyophilized ACT-246475A to be reconstituted with 1 mL of water for injection

Part A: Group 1; Part A: Group 2; Part A: Group 3; Part B: Group 1; Part B: Group 2; Part B: Group 3; Part C: Group 1; Part C: Group 2; Part C: Group 3

Clopidogrel DRUG

Tablet for oral administration (300 or 600 mg)

Part A: Group 1; Part A: Group 2; Part A: Group 3

Prasugrel DRUG

Tablet for oral administration (60 mg)

Part B: Group 1; Part B: Group 2; Part B: Group 3

Placebo DRUG

Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution

Part A: Group 1; Part A: Group 2; Part A: Group 3; Part B: Group 1; Part B: Group 2; Part B: Group 3; Part C: Group 1; Part C: Group 2; Part C: Group 3

Ticagrelor DRUG

Tablet for oral administration (180 mg)

Part C: Group 1; Part C: Group 2; Part C: Group 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Viatris Innovation GmbH: lead

Study Sites (1)

Biotrial Inc

Newark, New Jersey, 07103, United States

Location

Related 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):755-766. doi: 10.1055/s-0040-1721773. Epub 2021 Jan 7.

  PMID: 33412611 RESULT

MeSH Terms

Interventions

selatogrel; Clopidogrel; Prasugrel Hydrochloride; Ticagrelor

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Clinical Trials

  Viatris Innovation GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 13, 2018
• Study Start: January 24, 2018
• Primary Completion: May 20, 2019
• Study Completion: May 29, 2019
• Last Updated: July 3, 2025

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)