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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Multi-center, Double-blind, Randomized, Placebo-controlled Study to Assess the Pharmacodynamics, Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Injection of ACT-246475 in Adults With Stable Coronary Artery Disease

Conditions
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Stable Coronary Artery Disease

Intervention / Treatment
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* Drug: Selatogrel
* Drug: Placebo
* Drug: Selatogrel


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: 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). Main Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selatogrel 8 mg<br>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<br>* 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.<br>* Other names: ACT-246475;|
| Experimental: Selatogrel 16 mg<br>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<br>* 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) will be reconstituted with 1 mL of water for injection.<br>* Other names: ACT-246575;|
| Placebo Comparator: Placebo<br>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<br>* Matching placebo for subcutaneous administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Selatogrel Plasma Concentration (Cmax) | 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. | Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours | 
| Time to Reach Maximum Selatogrel Plasma Concentration (Tmax) | Time after subcutaneous injection to reach the maximum observed selatogrel plasma concentration (Cmax). | 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) | 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. | Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic coronary syndrome