A Randomized, Placebo-controlled, Investigator- and Participant-blinded Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of HSY244 in Participants With Atrial Fibrillation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Number of Participants With Conversion to Sinus Rhythm for at Least 1 Minute Within 90 Minutes From the Start of Study Drug Administration.
研究概览
简要总结
This was a randomized, placebo-controlled, investigator- and participant-blinded study to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of HSY244 in participants with atrial fibrillation (AF), with and without heart failure (HF).
详细描述
A screening period of up to 3 days (72 hours) was used to assess eligibility. After eligibility was confirmed, patients were randomized to either HSY244 or placebo. Prior to study drug administration, pre-dose assessments were completed. After the start of study drug administration, the participant was monitored for cardioversion to sinus rhythm. If a participant was still in AF at 90 minutes after the start of study drug administration, direct current cardioversion was planned to be applied at a time deemed appropriate by the investigator.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At screening, written informed consent were required to be obtained before any assessment was performed and only participants able to provide written informed consent themselves were included in this study.
- •Hemodynamically stable men and women (either of non-child-bearing potential or child bearing potential with highly effective contraception) between 18 and 80 years of age (inclusive) at screening with a clinical indication for direct current cardioversion of AF.
- •At screening, current episode of AF had been ongoing for ≥6 hours and ≤60 days
- •Successful initiation and achievement of therapeutic levels of national guideline and institution-specific anticoagulation therapy as appropriate for the duration of the AF episode and risk for the participant.
- •Completion of national guideline and institution-specific imaging evaluation for left atrial thrombi as appropriate for the duration of AF episode and risk for the participant.
- •At screening, participants were required to weigh at least 60 kg to participate in the study and were required to have a body mass index (BMI) within the range of 18 - 45 kg/m^
- •BMI = Body weight (kg) / [Height (m)]^2
- •At screening, vital signs (systolic blood pressure and pulse rate) were assessed in the sitting position. Sitting vital signs were required to be within the following ranges (exclusive):
- •systolic blood pressure between 100-160 mmHg and diastolic blood pressure 60-100 mmHg
- •pulse rate (ventricular rate) between 60-120 bpm.
排除标准
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 4 days after stopping of investigational drug.
- •Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for 96 hours after study drug administration. A condom was required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of the investigational drug via seminal fluid to their partner. In addition, male participants could not donate sperm for the time period specified above.
- •Use of any anti-arrhythmic class I or III drug (including Ranolazine [Ranexa]) within 5 half lives before randomization; including use of amiodarone within 3 months before randomization.
- •At screening, history of current diagnosis of ECG abnormalities or cardiac rhythm disorders as determined by the Investigator's interpretation of the ECG findings indicating a significant risk for participating in the study, such as:
- •History of Torsades de Pointes (TdP), any other polymorphic ventricular tachycardia, sustained monomorphic ventricular tachycardia, long QT syndrome, or Brugada syndrome.
- •Wolfe-Parkinson-White (WPW) syndrome
- •In the absence of a complete bundle branch block a resting QTcF >460 msec for men and >470 msec for women (mean of ≥ 5 consecutive QT intervals)
- •In the presence of a complete bundle branch block, a prolonged QTcF or JTc that, in the opinion of the investigator, may pose a risk to patient safety
- •Third-degree (complete) heart block, or second-degree Mobitz type II heart block
- •Attempted or unsuccessful cardioversion within 2 weeks prior to randomization.
- •Presence of known severe mitral regurgitation and/or known severely dilated left atrium.
- •Pre-existing or tachycardia-induced moderate to severe cardiac dysfunction (New York Heart Association Class III and IV).
- •History within the preceding 3 months prior to randomization of: myocardial infarction, unstable angina, cardiac surgery, or a percutaneous coronary intervention.
- •History of a confirmed stroke or transient ischemic attack (TIA).
- •History or current diagnosis of any seizure disorder, epilepsy, significant head trauma, or other disorders increasing the risk for seizures.
- •History or current diagnosis of a major neurologic or psychiatric disorder that, in the opinion of the investigator, poses a risk to patient safety to participate.
研究组 & 干预措施
HSY244
HSY244 150 mg concentrate solution for injection via intravenous infusion
干预措施: HSY244 (Drug)
Placebo
Placebo concentrate solution for injection via intravenous infusion
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Conversion to Sinus Rhythm for at Least 1 Minute Within 90 Minutes From the Start of Study Drug Administration.
时间窗: 90 minutes from the start of study drug administration
Conversion to sinus rhythm was monitored using a Holter monitoring device through 90 minutes after the start of study drug administration. If a participant had been monitored for at least 45 minutes and did not convert to sinus rhythm for at least one minute, the primary endpoint was defined as 'no'. If a participant converted to sinus rhythm for at least one minute at any time during the post-treatment 90 minutes observation period, regardless of the length of time monitored, the primary endpoint was to be defined as 'yes'.
次要结局
- Time to Reach the Maximum Concentration After Drug Administration (Tmax)(Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5)
- Area Under the Plasma Concentration-time Curve (AUClast)(Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5)
- Maximum Observed Plasma Concentration (Cmax)(Day 1 (0 min (pre-dose), 15 min (end of infusion), 30 min , 60 min, 90 min and 180 min) and Day 5)