A Double-blind, Randomized, Placebo-controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Macitentan in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 178
- 试验地点
- 53
- 主要终点
- Forced Vital Capacity (FVC) at Baseline and End of Period 1
研究概览
简要总结
The AC-055B201/MUSIC study is a Phase II study, comparing one dose of ACT-064922 (macitentan) 10 mg with placebo in patients with idiopathic pulmonary fibrosis (IPF). The main study objective is to demonstrate that macitentan positively affects the forced vital capacity (FVC) in comparison with placebo in patients with idiopathic pulmonary fibrosis (IPF).
The secondary objectives are to evaluate the effect of macitentan on the time to disease worsening or death in patients with IPF, and to evaluate the benefit/risk profile of macitentan in the treatment of patients with IPF.
详细描述
The study included two treatment periods: Period 1 (fixed duration) from randomization up to the primary endpoint evaluation (Month 12 or earlier in case of premature discontinuation of study drug) and Period 2 (variable duration) from the primary endpoint evaluation visit up to the end of study (EOS). EOS occurred when the last patient randomized and not prematurely discontinued completed Period 1.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent.
- •Male or female patients of at least 18 years of age (females of child-bearing potential must use a reliable method of contraception).
- •IPF diagnosis within 3 years prior to randomization, proven according to the American Thoracic Society/European Respiratory Society consensus conference criteria, with surgical lung biopsy.
排除标准
- •Interstitial lung disease due to conditions other than IPF.
- •Presence of extensive honeycombing on Baseline high-resolution computed tomography (HRCT) scan performed within 3 months prior to randomization.
- •Severe concomitant illness limiting life expectancy (< 1 year).
- •Severe restrictive lung disease: forced vital capacity (FVC) < 50% predicted, or FVC < 1.2 liter.
- •Diffusing capacity of the lung for carbon monoxide (DLCO) < 30% predicted.
- •Residual volume ≥ 120% predicted.
- •Obstructive lung disease: forced expiratory volume in 1 second (FEV1)/FVC) < 0.
- •Documented sustained improvement of the patient's IPF condition up to 12 months prior to randomization with or without IPF-specific therapy.
- •Recent pulmonary or upper respiratory tract infection (up to 4 weeks prior to randomization).
- •Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., pulmonary function tests).
- •Chronic heart failure with New York Heart Association class III/IV or known left ventricular ejection fraction < 25%.
- •Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- •Estimated creatinine clearance < 30 mL/min.
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase > 1.5 x upper limit of normal.
- •Hemoglobin < 75% of the lower limit of the normal range.
- •Systolic blood pressure < 100 mmHg.
- •Pregnant or breast-feeding.
- •Current drug or alcohol dependence.
- •Chronic treatment with the following drugs (within 4 weeks of randomization):
- •Oral corticosteroids (> 20 mg/day of prednisone or equivalent),
- •Immunosuppressive or cytotoxic drugs including cyclophosphamide and azathioprine,
- •Antifibrotic drugs including pirfenidone, D penicillamine, colchicine, tumor necrosis factor α blockers, imatinib and interferon γ,
- •Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day).
- •Oral anticoagulants prescribed for IPF.
- •Treatment with endothelin receptor antagonists within 4 weeks prior to randomization.
- •Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors).
- •Treatment with Cytochrome P450 3A inducers within 4 weeks prior to randomization.
- •Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
- •Planned treatment, or treatment with another investigational drug within 4 weeks prior to randomization.
研究组 & 干预措施
ACT-064922
ACT-064922 tablet (macitentan), 10 mg, once daily
干预措施: ACT-064992 (macitentan) (Drug)
Placebo
Matching placebo, once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Forced Vital Capacity (FVC) at Baseline and End of Period 1
时间窗: 12 months
FVC was measured at baseline and at the end of Period 1. The same equipment and tester were used during the course of the study. The equipment was calibrated and the calibration documented prior to each patient's measurement. The person responsible for conducting the pulmonary function tests was required to comply with the study guidelines and the American Thoracic Society/European Respiratory Society joint criteria on lung function testing.
次要结局
- Number of Patients at Risk of Event of Disease Worsening or Death up to the End of Study(Up to end of study (Up to 24 months))