A 24 Week, Randomized, Double Blind, Multicenter, Placebocontrolled Efficacy, Safety, Tolerability and PK Trial of Nilotinib (Tasigna®, AMN107) in Pulmonary Arterial Hypertension (PAH)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Change in Pulmonary Vascular Resistance (PVR)
研究概览
简要总结
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months treatment with nilotinib will significantly reduce pulmonary artery resistance.
详细描述
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •World Health Organization (WHO) Functional Class II or III
- •6MWD ≥ 150 m and ≤ 450 m at screening
- •Current diagnosis of PAH according to Dana Point 2008 Meeting
- •Inadequate clinical response on one or more class(es) of PAH drug
- •Stabilization of pulmonary hypertension medications for ≥ 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.
排除标准
- •Women of child-bearing potential not practicing birth control
- •In treatment with chronic nitric oxide therapy
- •Pre-existing lung disease
- •Use of drugs prolonging the QT interval or strong CYP3A4 inhibitors
- •Long QT syndrome or QTc > 450 ms males; > 470 ms females.
- •WHO Class IV
- •Pulmonary capillary wedge pressure > 15 mm Hg
- •Other diagnosis of PAH in WHO Diagnostic Group 1
- •PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels)
- •Thrombocytopenia < 50 x109/L (50 x 103/µL)
- •Uncontrolled systemic arterial hypertension, systolic > 160 mm Hg or diastolic >90 mm Hg
- •Any advanced, severe, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Nilotinib
Participants in cohort 1 were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days. Participants in cohort 2 were assigned to receive nilotinib 300 mg during 168 days
干预措施: Nilotinib (Drug)
Placebo
Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
干预措施: Placebo to nilotinib (Drug)
结局指标
主要结局
Change in Pulmonary Vascular Resistance (PVR)
时间窗: 168 days
Change in pulmonary vascular resistance is measured via right heart catheter assessment according to local hospital procedures. It assesses several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Vascular Resistance (PVR). Study was prematurely terminated and not powered for efficacy.
次要结局
- Change in Six-Minute Walk Distance (6MWD) From Baseline(Baseline, 168 days)
- Total Number of Adverse Events and Serious Adverse Events(168 days)