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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 346
- 试验地点
- 33
- 主要终点
- Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
Selatogrel 16 mg
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.
干预措施: Selatogrel (Drug)
Selatogrel 8 mg
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.
干预措施: Selatogrel (Drug)
结局指标
主要结局
Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
时间窗: 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".
次要结局
- Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)(Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours)
- Maximum 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)(Pre-dose, and from 15 minutes after administration of the subcutaneous injection up to 24 hours post-dose)