A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 85
- 主要终点
- Change From Baseline in Six-minute Walk Distance (6MWD).
研究概览
简要总结
Ambrisentan is an endothelin receptor antagonist used for the treatment of pulmonary hypertension (PH). Based on research suggesting a role for endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the poor prognosis for patients with IPF who are also diagnosed with PH, this study was designed to evaluate the effectiveness and safety of ambrisentan in that patient population.
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
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Weight ≥ 40 kg at screening
- •Diagnosis of IPF based on modified American Thoracic Society-European Respiratory Society guidelines
- •Diagnosis of PH based on the following hemodynamic requirements: mean pulmonary artery pressure (mPAP ≥ 25 mm Hg; pulmonary vascular resistance > 240 dyne.sec/cm^5; pulmonary capillary wedge pressure or left ventricular end-diastolic pressure ≤ 15 mm Hg
- •Forced vital capacity (FVC) ≥ 40%
- •Able to walk at least 50 meters during two 6-minute walk tests
- •If receiving calcium channel blockers, low-dose oral corticosteroids, immunosuppressive, cytoxic, or antifibrotic drugs dose must have been stable.
排除标准
- •Diagnosis of PH primarily due to an etiology other than IPF
- •Surgical lung biopsy diagnosis other than Usual Interstitial Pneumonia
- •Other known cause of interstitial lung disease
- •Evidence of significant obstructive lung disease
- •Recent hospitalization for an acute exacerbation of IPF
- •Recent active pulmonary or upper respiratory tract infection
- •Left ventricular ejection fraction < 40%
- •Serum creatinine ≥ 2.5 mg/dL
- •Required hemodialysis, peritoneal dialysis, or hemofiltration
- •Female subject who was pregnant or breastfeeding
- •Recent treatment for PH with an endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor, or prostacyclin derivative
- •Recent treatment with high dose oral corticosteroids
- •Recent treatment (within 4 weeks prior to screening) with imatinib mesylate (Gleevec)
- •Alanine aminotransferase or aspartate aminotransferase lab value that was greater than 1.5 x the upper limit of the normal range
- •Discontinued other ERA treatment for any adverse reaction other than those associated with liver function test abnormalities
研究组 & 干预措施
Ambrisentan
Participants were randomized to receive ambrisentan treatment at an initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 52 weeks
干预措施: Ambrisentan (Drug)
Placebo
Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks.
干预措施: Ambrisentan (Drug)
Placebo
Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Six-minute Walk Distance (6MWD).
时间窗: Baseline to Week 16
The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.
次要结局
- Long-term Survival(Week 48)
- Transition Dyspnea Index (TDI)(Baseline to Week 16)
- Change From Baseline in WHO Functional Class(Baseline to Week 16)
- Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted(Baseline to Week 16)
- Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)(Baseline to Week 16)
- Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise(Baseline to Week 16)
- Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted(Baseline to Week 16)
- Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36)(Baseline to Week 16)
- Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ)(Baseline to Week 16)