A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Coronary Artery Disease

NCT03384966 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ID-076A2012017-003332-36
• Study Type: interventional
• Target: 346
• Locations: 8 countries
• Sites: 20

Brief Summary

The goal of this study is to find out if a drug called selatogrel (ACT-246475) can prevent platelets from binding together when administered by an injection under the skin in the thigh or in the belly. Another goal is to know how fast and for how long selatogrel (ACT-246475) works and if there is a difference if the drug is injected in the thigh or in the belly. This study will also help to find out more about the safety of this new drug.

Conditions

Stable Coronary Artery Disease

Keywords

Chronic coronary syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation

  The pharmacodynamic response was determined by measuring the inhibition of platelet aggregation, using VerifyNow®. The VerifyNow® is a point-of-care test measuring platelet reactivity. The results are expressed as P2Y12 reaction units (PRU). The target of 100 PRU corresponds to 80% inhibition of ADP-induced platelet aggregation. A participant with a PRU of less than 100 starting from 30 minutes after the administration of study treatment and lasting for at least 3 hours was considered a "responder".

  From 15 minutes after administration of the subcutaneous injection up to 24 hours

Secondary Outcomes (3)

• Maximum Selatogrel Plasma Concentration (Cmax)

  Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours

• Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)

  Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours

• Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24)

  Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours post-dose

Other Outcomes (4)

• Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen)

  From 15 minutes after administration of the subcutaneous injection up to 24 hours

• Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis

  From 15 minutes after administration of the subcutaneous injection up to 24 hours

• Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA)

  Pre-dose, and from 30 minutes after administration of the subcutaneous injection up to 8 hours

Study Arms (3)

Selatogrel 8 mg

EXPERIMENTAL

Selatogrel (ACT-246475) is given as a single subcutaneous dose of 8 mg administered in a volume of 0.8 mL. Administration will be performed at the investigational site by qualified personnel.

Drug: Selatogrel

Selatogrel 16 mg

EXPERIMENTAL

Selatogrel (ACT-246475) is given as a single subcutaneous dose of 16 mg administered in a volume of 0.8 mL. Administration will be performed at the investigational site by qualified personnel.

Drug: Selatogrel

Placebo

PLACEBO COMPARATOR

Placebo matching ACT-246475 is supplied in sealed glass vials for reconstitution with water for injection. Placebo will be given as a single subcutaneous dose matching selatogrel to be administered in a volume of 0.8 mL. Administration will performed at the investigational site by qualified personnel.

Drug: Placebo

Interventions

Selatogrel DRUG

Selatogrel is a reversible P2Y12 receptor antagonist for subcutaneous administration. It is supplied in sealed glass vials at a strength of 20 mg. The vials with ACT-246475A (hydrochloride salt of ACT-246475) or matching placebo will be reconstituted with 1 mL of water for injection. Further dilution with 1 mL sodium chloride (NaCl) 0.9% will be performed for preparation of the dose of 8 mg selatogrel.

Also known as: ACT-246475

Selatogrel 8 mg

Placebo DRUG

Matching placebo for subcutaneous administration.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to any study-mandated procedure.
• Male and female subjects aged from 18-85 years, inclusive.
• For women of childbearing potential: Negative urine pregnancy test at Visit 1 and at Visit 2 before randomization.
• Stable Coronary artery disease (CAD) defined by the presence of any of the following conditions:
• History of CAD with coronary artery stenosis on coronary angiogram ≥50%.
• Previously documented myocardial infarction occurring more than 3 months prior to randomization.
• Antiplatelet background therapy stable for at least 1 month prior to randomization.
• Body weight ≥ 40.0 kg (88.2 lbs).

You may not qualify if:

• Acute coronary syndrome, percutaneous coronary intervention or any intervention for peripheral artery disease within 3 months prior to randomization.
• Acute ischemic stroke or transient ischemic attack (TIA) within 3 months prior to randomization.
• Active internal bleeding, or medical history of recent (\< 1 month) bleeding disorders or conditions associated with high risk of bleeding (e.g., clotting disturbances, gastrointestinal bleed, hemoptysis).
• Hemoglobin ≤ 10 g/dL at screening.
• Loss of at least 250 mL of blood within 3 months of screening.
• Use of anticoagulants (oral, parenteral) or fibrinolytic therapy within 24 h prior to screening (Visit 1).
• Known platelet disorders (e.g., thrombasthenia, thrombocytopenia, von Willebrand disease).
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Viatris Innovation GmbH: lead

Study Sites (20)

University of Florida (UF) Jacksonville

Jacksonville, Florida, 32209, United States

Location

Florida Hospital Tampa - Pepin Heart Institute

Tampa, Florida, 33613, United States

Location

NorthShore University

Chicago, Illinois, 73104, United States

Location

Indiana University School of Medicine - Krannert Institute of Cardiology

Indianapolis, Indiana, 46202, United States

Location

Inova Cardiology

Lutherville, Maryland, 21093, United States

Location

Mount Sinai Hospital (New York)

New York, New York, 10029, United States

Location

Inova Center for Thrombosis Research and Translational Medicine

Falls Church, Virginia, 22042, United States

Location

Institut de Cardiologie de Montréal

Montreal, Quebec, H1T 1C8, Canada

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Universitats-Herzzentrum

Bad Krozingen, 79189, Germany

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Maastricht UMC

Maastricht, 6229 HX, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, 3435 CM, Netherlands

Location

National Heart Centre Singapore

Singapore, 169609, Singapore

Location

Sahlgrenska University Hospital

Gothenburg, 40530, Sweden

Location

Uppsala University Hospital

Uppsala, 18288, Sweden

Location

Freeman Hospital - Cardiothoracic Department

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Sheffield Teaching Hospitals

Sheffield, S5 7AU, United Kingdom

Location

East & North Hertfordshire NHS Trust - Lister Hospital

Stevenage, SG14AB, United Kingdom

Location

Related Publications (1)

• Storey RF, Gurbel PA, Ten Berg J, Bernaud C, Dangas GD, Frenoux JM, Gorog DA, Hmissi A, Kunadian V, James SK, Tanguay JF, Tran H, Trenk D, Ufer M, Van der Harst P, Van't Hof AWJ, Angiolillo DJ. Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes. Eur Heart J. 2020 Sep 1;41(33):3132-3140. doi: 10.1093/eurheartj/ehz807.

  PMID: 31994703 DERIVED

MeSH Terms

Interventions

selatogrel

Limitations and Caveats

Blood was collected with phenylalanine-proline-arginine-chloromethyl ketone as anticoagulant. Any direct comparison of absolute PRU values obtained in this study with those published from studies of other P2Y12 inhibitors should take this into account.

Results Point of Contact

• Title: Viatris Innovation Clinical Trial Information
• Organization: Viatris Innovation GmbH

viatrisinnovationclinicaltrials@viatris.com

+41 58 844 07 44

Study Officials

• Clinical Trials

  Viatris Innovation GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinding will apply to treatment (ACT-246475 vs placebo). The dose (8 mg vs 16 mg) will be single blinded (subject blinded). The site for the sub-cutaneous injection (thigh vs abdomen) will not be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: December 28, 2017
• Study Start: January 24, 2018
• Primary Completion: August 18, 2018
• Study Completion: September 18, 2018
• Last Updated: July 9, 2025
• Results First Posted: May 17, 2021

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); GB (3); DK (2); DE (1); SE (2); SG (1); CA (1); US (7)