A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Assess the Safety, Tolerability and Pharmacokinetics of Serelaxin When Added to Standard Therapy in Japanese Acute Heart Failure Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy
研究概览
简要总结
This is a multicenter, randomized, double-blind, placebo-controlled study to assess safety, tolerability and pharmacokinetics and to explore efficacy of IV infusion of 10 µg/kg/day and 30 µg/kg/day serelaxin for 48 hours compared to placebo, when added to the standard therapy, in approximately 45 Japanese AHF patients.
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)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent must be obtained before any study-specific assessment is performed.
- •Male or female ≥20 years of age, with body weight ≥30 kg and ≤160 kg
- •Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening:
- •Dyspnea at rest or with minimal exertion
- •Pulmonary congestion on chest radiograph
- •BNP ≥350 pg/mL or NT-proBNP ≥1,400 pg/mL
- •SBP ≥125 mmHg at the start and at the end of screening
- •Able to be randomized within 16 hours from presentation to the hospital, including the emergency department
- •Received intravenous (IV) furosemide of at least 40 mg (or equivalent) at any time between presentation (this include outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute heart failure (HF) episode.
- •Impaired renal function defined as an estimated glomerular filtration rate (eGFR) between presentation and randomization of ≥ 25 and≤ 75 mL/min/1.73 m2, calculated using the Japanese formula
排除标准
- •Dyspnea primarily due to non-cardiac causes
- •Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
- •Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.
- •AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate <45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of >130 beats per minute.
研究组 & 干预措施
Serelaxin 10 mcg/kg/Day
Participants received 10 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours.
干预措施: Serelaxin (Drug)
Serelaxin 30 mcg/kg/Day
Participants received 30 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours.
干预措施: Serelaxin (Drug)
Placebo
Participants received continuous i.v. infusion of placebo matched to serelaxin for 48 hours.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy
时间窗: From start of study treatment up to Day 5 (for AEs); From start of study treatment up to Day 14 (for SAEs)
AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. AEs leading to discontinuations, or requiring dose adjustment or interruptions and additional therapy were assessed.
Maximum Plasma Concentration (Cmax) of Serelaxin
时间窗: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Maximum plasma concentration (Cmax) was defined as the peak level of serelaxin, derived from plasma concentration-time data, using a non-compartmental model approach.
Weight Adjusted Clearance (CL) of Serelaxin
时间窗: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Weight adjusted clearance (CL) was defined as the total body clearance of serelaxin after drug administration. CL was calculated as nominal infusion rate divided by Css, using a non-compartmental model approach.
Concentration at Steady-state (Css) of Serelaxin
时间窗: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Concentration at steady-state (Css) was defined as concentration at the state of equilibrium obtained at the end of a certain number of administrations. Css of serelaxin in plasma was calculated by using a non-compartmental model approach.
次要结局
- Change From Baseline in Area Under the Curve (AUC) for Systolic Blood Pressure (SBP) Through 48 Hours of Infusion at Day 5(Baseline, 48 hours, Day 5)
- Change From Baseline in Aldosterone Levels Through Day 14(Baseline, Day 1, Day 2, Day 5, Day 14)
- Change From Baseline in Cystatin-C Levels Through Day 14(Baseline, Day 1, Day 2, Day 5, Day 14)
- Change From Baseline in High Sensitivity Troponin-T Levels Through Day 14(Baseline, Day 1, Day 2, Day 5, Day 14)
- Change From Baseline in NT-proBNP Levels Through Day 14(Baseline, Day 1, Day 2, Day 5, Day 14)
- Change From Baseline in Neutrophil Gelatinase-asc Lipocalin (NGAL) Levels Through Day 14(Baseline, Day 1, Day 2, Day 5, Day 14)