A Phase 2a, Double-Blind, Placebo-Controlled Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of RVT-1201 in Patients With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 23
- 主要终点
- Adverse events (AEs) and discontinuations due to AEs
研究概览
简要总结
This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of RVT-1201 in patients with pulmonary arterial hypertension (PAH).
详细描述
This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of RVT-1201 in patients with pulmonary arterial hypertension (PAH).
Study participation for each patient will last approximately 3 months and will consist of a screening period (up to 28 days in duration), a baseline period (day 1, pre-dose), a 6-week treatment period, and a 2-week follow-up period.
The study will enroll approximately 36 patients at approximately 20 centers across the United States and Canada.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic PAH belonging to one of the following types:
- •Idiopathic
- •Heritable
- •Drug- or toxin- induced
- •Associated with one of the following: connective tissue disease or congenital heart disease
- •World Health Organization (WHO) Functional Class (FC) II or III
- •PAH diagnosed by right heart cardiac catheterization prior to Screening
- •Receiving standard of care treatment for PAH with oral monotherapy or dual therapy for at least 12 weeks prior to Screening at a dose which has been stable for at least 8 weeks prior to Screening
- •If on a diuretic, dose must be stable for at least 4 weeks prior to Screening, with no changes anticipated during study participation
- •6-Minute Walk Distance (6MWD) between 150 and 500 meters at Screening and Baseline visits
- •Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) level ≥ 300 pg/mL at Screening
- •Ability and willingness to give written informed consent and to comply with the requirements of the study
排除标准
- •PAH associated with human immunodeficiency virus (HIV) infection, portal hypertension or schistosomiasis
- •Other types of pulmonary hypertension (PH):
- •Pulmonary hypertension due to left heart disease (WHO PH Group 2)
- •Pulmonary hypertension due to lung diseases and/or hypoxia (WHO PH Group 3)
- •Chronic thromboembolic pulmonary hypertension (WHO PH Group 4)
- •Pulmonary hypertension with unclear multifactorial mechanisms (WHO PH Group 5)
- •Hospitalization for pulmonary hypertension within 12 weeks of screening
- •Cardiopulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Screening)
- •Prostanoid or prostacyclin receptor agonist therapy within 12 weeks of screening
- •Evidence of left-sided heart disease
- •If Pulmonary function tests were done prior to screening, Pulmonary function tests demonstrate obstructive or restrictive lung disease
- •Use of telotristat (Xermelo®) within the last 6 months
- •Use of any investigational drug within 30 days or five half-lives (whichever is longer) prior to Screening, or 90 days if an investigational drug for PAH
- •Have uncontrolled atrial fibrillation (AFib) or other uncontrolled arrhythmias
- •Body mass index (BMI) >45 kg/m2
- •Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception
研究组 & 干预措施
RVT-1201
RVT-1201 600 mg immediate-release tablet, administered orally twice daily with food for 6 weeks, in addition to the patient's current standard of care medication(s) for PAH (n=24 [Anticipated])
干预措施: RVT-1201 (Drug)
Placebo
Matching placebo tablet, administered orally twice daily with food for 6 weeks, in addition to the patient's current standard of care medication(s) for PAH (n=12 [Anticipated])
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse events (AEs) and discontinuations due to AEs
时间窗: 8 weeks
Incidence of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), and discontinuations due to AEs
次要结局
- Concentration of biomarkers of serotonin biosynthesis in urine(8 weeks)
- Area under the plasma concentration versus time curve (AUC) of KAR5417 (the active metabolite of RVT-1201)(6 weeks)
- Relationship between KAR5417 exposure and percent change from baseline in plasma concentrations of the serotonin-related biomarkers(6 weeks)
- Concentration of biomarkers of serotonin biosynthesis in plasma(8 weeks)
- Study drug (RVT-1201) and active metabolite (KAR5417) plasma concentrations(6 weeks)
- Relationship between KAR5417 exposure and percent change from baseline in urine concentrations of the serotonin-related biomarkers(6 weeks)