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Completed

NCT Number: NCT03384966

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

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.

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Key information

Conditions

Stable Coronary Artery Disease

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Institut de Cardiologie de Montréal, Montreal, Quebec, Canada

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Other names: ACT-246475

Placebo

Drug

Matching placebo for subcutaneous administration.

Primary outcomes

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

    Time frame: 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 outcomes

  1. Maximum Selatogrel Plasma Concentration (Cmax)

    Time frame: 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.

  2. Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)

    Time frame: 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).

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

    Time frame: 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.

Other outcomes

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

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

    The inhibition of platelet aggregation based on the route of administration, i.e. whether the pharmacodynamic response was different if selatogrel was administered subcutaneously in the thigh or in the abdomen, was analyzed.

    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".

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

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

    To assess the robustness of results for the pharmacodynamic response, the main analysis was repeated for the per protocol participants. 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".

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

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

    Light transmission aggregometry was used as complementary method to the VerifyNow® to evaluate the effect of selatogrel on platelet aggregation. Platelet aggregation was triggered by addition of Adenosine diphosphate (ADP) 20 µM (micromole per liter) and monitored over 6 minutes. Maximum Platelet Aggregation (MPA) to 20 μM ADP was assessed by light transmission aggregometry (LTA), an assay that measures platelet aggregation by determining the amount of light transmitted through a cuvette containing platelet-rich plasma stimulated with 20 µM ADP, relative to platelet-poor plasma (100% light transmittance). A lower MPA % reflects stronger platelet inhibition, whereas a higher MPA % reflects weaker inhibition.

  4. Number of Participants With Bleeding Events

    Time frame: From study treatment administration on Day 1 up to 48 hours

    Treatment-emergent adverse events in the category "Haemorrhage (excluding laboratory terms)" were of special interest and their incidence listed below.

    The role of the Independent Safety Event Committee was to monitor unblinded safety data obtained in the study, with a specific focus on study-drug-related clinically relevant major bleeding events, occurring within 48 hours after dosing (i.e. the treatment period).

Sponsors and collaborators

Lead sponsor

Viatris Innovation GmbH

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2018
Study completion
2018
First posted
Dec 28, 2017
Registry last updated
Jul 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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