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

Phase 2

Completed

• Conditions: Stable Coronary Artery Disease
• Interventions: Drug: Placebo; Drug: Selatogrel

• Registration Number: NCT03384966
• Lead Sponsor: Idorsia Pharmaceuticals Ltd.

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.

Detailed Description

To investigate the pharmacodynamic (PD) and pharmacokinetic (PK) properties of selatogrel in patients with atherosclerotic disease, the present study will be conducted in patients with chronic coronary syndromes (CCS). Assessment in a population of patients with CCS allows better control and stability of concomitant treatments, and therefore more accurate characterization of the pharmacodynamic and pharmacokinetic profiles of selatogrel in the presence of background antiplatelet therapies.

The study will have 3 periods: a screening period of up to 21 days prior to randomization, a treatment period of 2 days from randomization (Day 1) to 24 hours post dose (Day 2), and a follow-up period from Day 3 to the safety follow-up telephone call 28 to 35 days after single administration of study drug (End-of-Study).

Study Timeline

• Study First Submitted: 2017-12-20
• Study First Submitted QC: 2017-12-20
• Study First Posted: 2017-12-28
• Study Start: 2018-01-24
• Primary Completion: 2018-08-18
• Study Completion: 2018-09-18
• Disposition First Submitted: 2019-07-11
• Disposition First Submitted QC: 2019-07-11
• Disposition First Posted: 2019-07-17
• Results First Submitted: 2021-04-23
• Results First Submitted QC: 2021-04-23
• Results First Posted: 2021-05-17
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-15
• Last Update Posted: 2022-11-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 346

Inclusion Criteria

1. Signed informed consent prior to any study-mandated procedure.

2. Male and female subjects aged from 18-85 years, inclusive.

3. For women of childbearing potential: Negative urine pregnancy test at Visit 1 and at Visit 2 before randomization.

4. Stable Coronary artery disease (CAD) defined by the presence of any of the following conditions:

   1. History of CAD with coronary artery stenosis on coronary angiogram ≥50%.
   2. Previously documented myocardial infarction occurring more than 3 months prior to randomization.

5. Antiplatelet background therapy stable for at least 1 month prior to randomization.

6. Body weight ≥ 40.0 kg (88.2 lbs).

Main

Exclusion Criteria

1. Acute coronary syndrome, percutaneous coronary intervention or any intervention for peripheral artery disease within 3 months prior to randomization.
2. Acute ischemic stroke or transient ischemic attack (TIA) within 3 months prior to randomization.
3. 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).
4. Hemoglobin ≤ 10 g/dL at screening.
5. Loss of at least 250 mL of blood within 3 months of screening.
6. Use of anticoagulants (oral, parenteral) or fibrinolytic therapy within 24 h prior to screening (Visit 1).
7. Known platelet disorders (e.g., thrombasthenia, thrombocytopenia, von Willebrand disease).
8. Pregnant or breastfeeding women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
Selatogrel 8 mg	Selatogrel	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.
Selatogrel 16 mg	Selatogrel	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation	From 15 minutes after administration of the subcutaneous injection up to 24 hours	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".

Secondary Outcome Measures

Name	Time	Method
Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)	Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours	Time after subcutaneous injection to reach the maximum observed selatogrel plasma concentration (Cmax).
Maximum Selatogrel Plasma Concentration (Cmax)	Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours	The Cmax is the peak concentration of selatogrel in the plasma after subcutaneous injection.; The pharmacokinetic parameters of selatogrel (ACT-246475) were derived by non-compartmental analyses of the plasma concentration-time profiles.
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	The area under the plasma concentration-time curve is the integral of the concentration-time curve after subcutaneous injection of selatogrel.; The plasma pharmacokinetic parameters of selatogrel (ACT-246475) were derived by non-compartmental analyses of the plasma concentration-time profiles.

Trial Locations

Locations (20)

University of Florida (UF) Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Florida Hospital Tampa - Pepin Heart Institute; 🇺🇸 Tampa, Florida, United States

NorthShore University; 🇺🇸 Chicago, Illinois, United States

Indiana University School of Medicine - Krannert Institute of Cardiology; 🇺🇸 Indianapolis, Indiana, United States

Institut de Cardiologie de Montréal; 🇨🇦 Montréal, Quebec, Canada

Inova Cardiology; 🇺🇸 Lutherville, Maryland, United States

Inova Center for Thrombosis Research and Translational Medicine; 🇺🇸 Falls Church, Virginia, United States

Mount Sinai Hospital (New York); 🇺🇸 New York, New York, United States

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Universitats-Herzzentrum; 🇩🇪 Bad Krozingen, Germany

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands

Maastricht UMC; 🇳🇱 Maastricht, Netherlands

National Heart Centre Singapore; 🇸🇬 Singapore, Singapore

St. Antonius Ziekenhuis; 🇳🇱 Nieuwegein, Netherlands

Sahlgrenska University Hospital; 🇸🇪 Göteborg, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Freeman Hospital - Cardiothoracic Department; 🇬🇧 Newcastle Upon Tyne, United Kingdom

Sheffield Teaching Hospitals; 🇬🇧 Sheffield, United Kingdom

East & North Hertfordshire NHS Trust - Lister Hospital; 🇬🇧 Stevenage, United Kingdom

Rigshospitalet; 🇩🇰 Copenhagen, Denmark