A 12-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 349
- 试验地点
- 77
- 主要终点
- Six Minute Walk Distance (6MWD)
研究概览
简要总结
This study was an international, multicenter, randomized (2:1 active:placebo), double-blind, placebo-controlled study in subjects with PAH who were NOT currently receiving approved therapy for their PAH. Study visits occurred at 4 week intervals for 12 weeks (with an additional visit at Week 11) with the key measure of efficacy being the 6-minute walk test. Study procedures included routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. Two optional substudies were also a part of FREEDOM-M at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 12 and a genetics and biomarkers substudy with blood samples collected at Baseline and Week 12.
Patients who completed all assessments for 12 weeks were also eligible to enter an open-label, extension phase study (FREEDOM - EXT).
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
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between 12 and 75 years of age, inclusive.
- •Body weight at least 40 kg with a Body Mass Index < 45
- •PAH that is either idiopathic/heritable; associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); associated with collagen vascular disease; associated with HIV.
- •Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
- •Baseline 6-minute walk distance between 200 and 425 meters, inclusive.
- •Reliable and cooperative with protocol requirements.
排除标准
- •Nursing or pregnant.
- •Currently receiving an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, or prostacyclin within 30 days of Baseline.
- •PAH due to conditions other than noted in the above inclusion criteria.
- •History of uncontrolled sleep apnea, renal insufficiency, anemia, left sided heart disease, uncontrolled systemic hypertension, or parenchymal lung disease.
- •Use of an investigational drug within 30 days of Baseline.
研究组 & 干预措施
UT-15C (oral treprositnil)
Subjects receive UT-15C (oral treprostinil) twice daily.
干预措施: Oral treprostinil (UT-15C) Sustained Release Tablets (Drug)
Placebo
Subjects receive placebo (sugar pill) twice daily.
干预措施: Placebo (Other)
结局指标
主要结局
Six Minute Walk Distance (6MWD)
时间窗: Baseline and Week 12
Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 12, correlates with the historical clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS). The six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug. The Hodges-Lehmann median difference between treatment groups was used to estimate the treatment effect on 6MWD from Baseline to Week 12. A rank-based methodology was used instead of parametric-based methodology to avoid statistical bias caused by extreme outliers resulting from the handling of data that are missing due to death or clinical worsening of PAH. It is a more robust estimator than the between-treatment difference in medians.
次要结局
- Symptoms of PAH(Baseline and Week 12)
- Six Minute Walk Distance (6MWD)(Baseline and Week 4)
- Clinical Worsening Assessment(Baseline and Week 12)
- Borg Dyspnea Score(Baseline and Week 12)
- Dyspnea-Fatigue Index(Baseline and Week 12)
- World Health Organization Functional Classification for PAH(Baseline and Week 12)