A Randomized, Participant- and Investigator-blinded, Placebo-controlled Study to Investigate Efficacy, Safety, and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 47
- 试验地点
- 18
- 主要终点
- Change From Baseline in Right Heard Catheterization Pulmonary Vascular Resistance (PVR) at Week 25
研究概览
简要总结
The purpose of this study was to explore the efficacy and safety of LTP001 in participants with pulmonary arterial hypertension (PAH) to determine if LTP001 had an adequate clinical profile to warrant further clinical development in this indication.
详细描述
This study was a non-confirmatory, randomized, participant- and investigator-blinded, placebo controlled trial evaluating the efficacy and safety of LTP001 on top of standard of care in participants with PAH.
The study included a screening period of up to 8 weeks, followed by a 24-week treatment phase with daily dosing and visits scheduled approximately every 4 weeks. One follow-up visit, which also served as the end-of-study visit, was conducted approximately 30 days after the conclusion of the treatment phase. The total duration of the study, from the beginning of the screening period to the end-of-study visit, was approximately 37 weeks.
A total of 44 participants were planned to be randomized in a 3:1 ratio to receive either LTP001 6 mg or placebo.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of PAH belonging to one of the following subgroups of the Clinical Classification Group 1 (WHO):
- •participants with idiopathic pulmonary arterial hypertension (IPAH)
- •Hereditary pulmonary arterial hypertension
- •Congenital heart disease (surgically repaired at least 12 months prior to screening)
- •drug or toxin induced (for example, anorexigen, or methamphetamine use).
- •Resting mean pulmonary arterial pressure (mPAP) > 25 mmHg; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure < 15 mmHg, as determined by right heart catheterization within 20 days of randomization.
- •Pulmonary Vascular Resistance > 6 Wood units (480 dynes s/cm-5), as determined by right heart catheterization within 20 days of randomization.
- •WHO Functional Class II-III
- •6MWD must be between 150 and 550 m (inclusive). The qualifying test needs to be within 20 days of randomization. To meet the above criterion additional six minute walk test (6MWT) may be performed up to a maximum of 3 tests in total prior to dosing; the minimal time difference between two tests should be at least 4 h.
- •Standard of care therapy which is stable at least 6 weeks prior to RHC and qualifying 6MWT assessment within 20 days of randomization. Standard of care includes one or more of the following treatments:
- •prostacyclin analogues and receptor agonists (if I.V., dose adjustments must be within 20% of initial stable dose)
- •endothelin receptor antagonists (ERAs)
- •phosphodiesterase type 5 inhibitors (PDE5i)
- •soluble guanylate cyclase (sGC) stimulators
排除标准
- •Participants with pulmonary hypertension (PH) in the Clinical Classification Groups 2-5 (WHO), and any PAH Group 1 subgroups not covered by Inclusion Criterion #
- •Participants with a history of left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease compromising left ventricular function and/or pulmonary venous hypertension or symptomatic coronary disease (non-symptomatic, revascularized coronary artery disease would be acceptable).
- •Participants with obstructive lung disease defined as: FEV1/FVC < 60% and FEV1 < 60% of predicted value after bronchodilator administration as well as participants with moderate or severe restrictive lung disease: Total Lung Capacity < 70% of predicted value. Testing must have occurred within 24months of screening. If historical testing is not available, then lung function testing must be conducted during the screening period.
- •Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity and execution of study procedures such as 6MWT (e.g., angina pectoris, claudication, musculoskeletal disorder, multiple sclerosis, need for walking aids).
研究组 & 干预措施
LTP001
Participants received LTP001, 6 mg, oral capsules, once daily in the morning for approximately 24 weeks
干预措施: LTP001 (Drug)
Placebo
Participants received LTP001 placebo capsules matching LTP001 orally once daily in the morning for approximately 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Right Heard Catheterization Pulmonary Vascular Resistance (PVR) at Week 25
时间窗: Baseline, Week 25
PVR was defined as the resistance against blood flow from the pulmonary artery to the left atrium measured in dyn.s.cm-5
次要结局
- Change From Baseline in Six Minute Walk Distance (6MWD)(Baseline, Weeks 13 and 25)
- Change From Baseline in Right Atrium (RA) Pressures at Week 25(Baseline, Week 25)
- Change From Baseline in Pulmonary Capillary Wedge Pressure at Week 25(Baseline, Week 25)
- Change From Baseline in Mean Pulmonary Artery Pressure at Week 25(Baseline, Week 25)
- Change From Baseline in Average Cardiac Output (CO) at Week 25(Baseline, Week 25)
- Change From Baseline in Fractional Area Change (FAC)(Baseline, Weeks 5, 13, and 25)
- Change From Baseline in Peak Velocity of Excursion (RV S')(Baseline, Weeks 5, 13, and 25)
- Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)(Baseline, Weeks 5, 13, and 25)
- Change From Baseline in Tricuspid Annular Systolic Velocity (TASV)(Baseline, Weeks 5, 13 and 25)
- Change From Baseline in EmPHasis-10(Baseline, Weeks 13 and 25)
- Change From Baseline in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT)(Baseline, Weeks 13 and 25)
- Maximum Observed Blood Concentrations (Cmax) for LTP001(Day 1 and Week 25 at 15, 45, and 120 minutes post-dose)
- Time to Reach Maximum Blood Concentrations (Tmax) of LTP001(Day 1 and Week 25 at 15, 45, and 120 minutes post-dose)
- Time to Clinical Worsening(Baseline up to approximately 30 weeks)
- Change From Baseline in N-terminal Fragment of the Prohormone B-type Natriuretic Peptide (NT-ProBNP)(Baseline to Week 29)