Clinical trial NCT03384966: A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Coronary Artery Disease
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stable Coronary Artery Disease
Keywords: Chronic coronary syndrome
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2017-12-28
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Main 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.

Primary outcomes:
measure: Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
timeFrame: From 15 minutes after administration of the subcutaneous injection up to 24 hours
Secondary outcomes:
measure: Maximum Selatogrel Plasma Concentration (Cmax)
timeFrame: Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours
measure: Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)
timeFrame: Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours
measure: Area Under the Plasma Concentration-time Curve of Selatogrel From Time Zero to 24 Hour Time Point (AUC0-24)
timeFrame: Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours post-dose
Other outcomes:
measure: Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation by Site of Treatment Administration (Thigh or Abdomen)
timeFrame: From 15 minutes after administration of the subcutaneous injection up to 24 hours
measure: Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation - Sensitivity Analysis
timeFrame: From 15 minutes after administration of the subcutaneous injection up to 24 hours
measure: Change From Baseline in Maximum Platelet Aggregation (MPA) as Measured by Light Transmission Aggregometry (LTA)
timeFrame: Pre-dose, and from 30 minutes after administration of the subcutaneous injection up to 8 hours
measure: Number of Participants With Bleeding Events
timeFrame: From study treatment administration on Day 1 up to 48 hours
Locations:
city: Jacksonville
country: United States
facility: University of Florida (UF) Jacksonville
state: Florida
city: Tampa
country: United States
facility: Florida Hospital Tampa - Pepin Heart Institute
state: Florida
city: Chicago
country: United States
facility: NorthShore University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine - Krannert Institute of Cardiology
state: Indiana
city: Lutherville
country: United States
facility: Inova Cardiology
state: Maryland
city: New York
country: United States
facility: Mount Sinai Hospital (New York)
state: New York
city: Falls Church
country: United States
facility: Inova Center for Thrombosis Research and Translational Medicine
state: Virginia
city: Montréal
country: Canada
facility: Institut de Cardiologie de Montréal
state: Quebec
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bad Krozingen
country: Germany
facility: Universitats-Herzzentrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Singapore
country: Singapore
facility: National Heart Centre Singapore
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital - Cardiothoracic Department
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals
city: Stevenage
country: United Kingdom
facility: East & North Hertfordshire NHS Trust - Lister Hospital
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.