A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of Different Doses of IW-1973 Over 12 Weeks in Patients With Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 196
- 试验地点
- 60
- 主要终点
- Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12
研究概览
简要总结
The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973 compared with placebo when administered daily for approximately 12 weeks to patients with HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in patients with HFpEF, with or without permanent or persistent atrial fibrillation.
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
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is an ambulatory male or female ≥45 years old at the Screening Visit
- •Patient has heart failure with ejection fraction (EF) of ≥40%
- •Patient has a peak VO2 measuring <80% of age- and sex-adjusted normal values
- •Patient has evidence in medical history supporting clinical heart failure syndrome consisting of at least 1 of the following:
- •Hospitalization or emergency department visit for heart failure within the past year
- •Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months
- •Echocardiographic evidence within the past 12 months of at least 2 of the following: left ventricular (LV) hypertrophy, left atrial (LA) enlargement, or diastolic dysfunction
- •Hemodynamic evidence of elevated filling pressures
- •Patient meets at least 2 of the following criteria at the Screening Visit:
- •Diagnosis of type 2 diabetes mellitus or prediabetes
- •History of hypertension
- •Body mass index (BMI) >30 kg/m2
- •Age ≥70 years
排除标准
- •Patient has had acute coronary syndrome or percutaneous coronary intervention within 30 days before Randomization
- •Patient has had cardiac transplantation or has cardiac transplantation planned during the study
- •Patient has had cardiac artery bypass graft, cardiac mechanical support implantation, or other cardiac surgery in the 3 months before the Screening Visit or planned during the study
- •Patient has severe chronic obstructive coronary disease as defined by chronic oxygen dependence
- •Patient had had heart failure hospitalization with discharge within 30 days before the Screening Visit
- •Patient has a history of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products
- •Patient has previously received IW-1973 in a study, or received an investigational drug during the 30 days or 5 half lives of that investigational drug (whichever is longer) before the Screening Visit, or is planning to receive another investigational drug at any time during the study
- •Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form
- •Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors
- •Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug
- •Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug
- •Other exclusion criteria per protocol
研究组 & 干预措施
IW-1973 High Dose
干预措施: IW-1973 (Drug)
Placebo
Placebo to match experimental drug
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Change From Baseline in Peak Oxygen Consumption (VO2) at Week 12
时间窗: Baseline and Week 12
Peak VO2 was obtained from Cardiopulmonary Exercise Test (CPET), which was used to evaluate the effect of praliciguat on peak exercise capacity. Baseline is defined as the last non-missing measurement prior to the first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the Week 12 value. Data were analyzed using an analysis of covariance (ANCOVA) model with treatment group and atrial fibrillation stratification factors as categorical variable terms and Baseline peak VO2 value as a covariate. Milliliter O2 per kilogram per minute = mL O2/kg/min
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Study Drug-related TEAEs
时间窗: Day 1 up to Day 113
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as those adverse events (AEs) that started or worsened in severity after the administration of study drug. Causality relationship to study drug was per Investigator assessment. Number of participants with TEAEs and study drug-related TEAEs is presented.
次要结局
- Change From Baseline in Ventilatory Efficiency at Week 12(Baseline and Week 12)
- Change From Baseline in 6-minute Walk Test (6MWT) Distance at Week 12(Baseline and Week 12)
- CPET Responders at Week 12(At Week 12)