A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of LTP001 in Healthy Adult Participants (Part A) and to Evaluate the Efficacy and Safety of LTP001 for the Treatment of Participants With Pulmonary Arterial Hypertension (Part B)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 232
- 试验地点
- 87
- 主要终点
- Part A- Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
研究概览
简要总结
A study to learn about the treatment LTP001 in healthy participants (Part A) and in participants with PAH (Part B)
详细描述
The CLTP001A12202 study will explore the safety, tolerability, and pharmacokinetics of LTP001 in healthy volunteers (Part A) and will evaluate the safety and efficacy (Part B) followed by safety extension in participants with pulmonary arterial hypertension.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part A Inclusion Criteria:
- •Healthy males and non-child-bearing potential females
排除标准
- •Clinically significant ECG or cardiac abnormalities, any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in the study Other protocol-defined inclusion/exclusion criteria may apply.
- •For Japanese cohorts: participants per protocol should be first generation Japanese or up to third generation Japanese as defined in inclusion criteria 7 of the protocol.
- •Part B Inclusion Criteria:
- •Confirmed diagnosis of PAH, pre-randomization PVR ≥400 dyn.sec.cm-5, treatment with stable doses of standard-of-care PAH therapies, 6-minute walk distance ≥ 150 m and ≤450 m.
- •Part B Exclusion Criteria:
- •Any surgical or medical condition which may place the participant at higher risk from his/her participation in the study Women of child-bearing potential unless they are using highly effective methods of contraception Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 24 hours after stopping study treatment.
- •History of hypersensitivity to any of the study treatments or excipients
- •Other protocol-defined inclusion / exclusion criteria may apply
研究组 & 干预措施
LTP001 Dose 1
干预措施: LTP (Drug)
LTP001 Dose 2
干预措施: LTP (Drug)
LTP001 Dose 3
干预措施: LTP (Drug)
Placebo
matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Part A- Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
时间窗: Baseline to Day 35
Safety endpoints, including vital signs, ECG, clinical laboratory evaluations and adverse events up to and including the end-of-study visit.
Part B-Treatment Period 1: Change in pulmonary vascular resistance (PVR)
时间窗: Baseline to Week 24
PVR is a hemodynamic variable of pulmonary circulation and is measured by right heart catheterization.
Part B-Treatment Period 2: Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
时间窗: From Day 1 until Week 106
Safety endpoints, including vital signs, ECG, clinical laboratory evaluations, treatment-emergent adverse events and discontinuations due to adverse events.
次要结局
- Part A- Maximum observed plasma concentrations (Cmax)(Baseline to Day 35)
- Part A- Time to reach maximum plasma concentration (Tmax)(Baseline to Day 35)
- Part A- Area under plasma concentration-time curve from time zero to the last measurable concentration sampling time (AUClast)(Baseline to Day 35)
- Part A- Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-inf])(Baseline to Day 35)
- Part A- Terminal elimination half-life (T1/2)(Baseline to Day 35)
- Part B-Treatment Period 1: Change in the Six-minute Walk Test (6MWT)(Baseline to Week 24)
- Part B-Treatment Period 1: Change in N-terminal pro-brain natriuretic peptide (NT-proBNP)(Baseline to Week 24)
- Part B-Treatment Period 1: Change in World Health Organization (WHO) functional class (FC)(Baseline to Week 24)
- Part B-Treatment Period 2: Change in the Six-minute Walk Test (6MWT)(Baseline to Month 18)
- Part B-Treatment Period 2: Change in World Health Organization (WHO) functional class (FC)(Baseline to Month 18)