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

• Sponsor: Idorsia Pharmaceuticals Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03430661
• Collaborator: (none)
• Enrollment: 77
• Location: 1
• Arms: 9
• Actual Duration (Months): 16.1
• Patients Per Site Per Month: 4.8

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ACT-246475; Drug: Clopidogrel; Drug: Prasugrel; Drug: Placebo; Drug: Ticagrelor	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Jan 24, 2018
• Actual Primary Completion Date: May 20, 2019
• Actual Study Completion Date: May 29, 2019

Arms and Interventions

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: Prasugrel; Tablet for oral administration (60 mg); Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
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: Prasugrel; Tablet for oral administration (60 mg); Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
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: Prasugrel; Tablet for oral administration (60 mg); Drug: Placebo; Matching ACT-246475 placebo will consist of sterile 0.9% w/v sodium chloride solution
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)

Outcome Measures

Primary Outcome Measures

1. 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. [From baseline up to 48 hours]

   - IPA%[MPA] will be calculated as mean change in percentage from baseline for each time point.

2. 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. [From baseline up to 48 hours]

   - 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Biotrial Inc	Newark	New Jersey	United States	07103

Sponsors and Collaborators

• Idorsia Pharmaceuticals Ltd.

Investigators

• Study Director: Clinical Trials, Idorsia Pharmaceuticals Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Idorsia Pharmaceuticals Ltd.
• ClinicalTrials.gov Identifier: NCT03430661
• Other Study ID Numbers: ID-076-103
• First Posted: Feb 13, 2018
• Last Update Posted: Jul 9, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Clopidogrel; Ticagrelor; Prasugrel Hydrochloride

Study Results

No Results Posted as of Jul 9, 2021