An Open-label Extension Study of Ralinepag in Patients With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 46
- 主要终点
- Change From Baseline in Pulmonary Vascular Resistance
研究概览
简要总结
This study was an open-label extension study to determine the long-term safety and tolerability of ralinepag in subjects with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) who have completed Study APD811-003, or who were assigned to receive placebo and were discontinued due to clinical worsening.
详细描述
This study was an open-label extension study to determine the long-term safety and tolerability of ralinepag in subjects with WHO Group 1 PAH who completed Study APD811-003. Subjects who completed Study APD811-003 and met eligibility criteria for Study APD811-007 were enrolled. Additionally, placebo-treated subjects who discontinued study drug treatment due to clinical worsening in Study APD811-003 were permitted to enroll in Study APD811-007, upon approval of the medical monitor, provided that all end of study procedures including right heart catheterization (RHC) were performed per the study protocol. The Week 25 Visit in Study APD811-003 served as the Baseline Visit for Study APD811-007.
All subjects enrolled in Study APD811-007 received open-label treatment with ralinepag. The starting dose and titration schedule were individually determined and in accordance with the starting dose and titration schedule optimized from Study APD811-003. Adjustments in the dose and titration schedule were made according to subject tolerability.
After an individual subject completed Study APD811-003 and that subject's database was locked, subject unblinding occurred. Subjects on active treatment (ralinepag) remained on their current dose and had onsite clinical assessments performed every 3 months until the subject was discontinued from the study.
Subjects in the placebo treatment group underwent a dose titration period until a stable, maximum tolerated dose (MTD) was reached (up to 9 weeks), followed by a treatment period after the MTD was determined during which monthly onsite clinic assessments were performed for the first 3 months and then every 3 months until the subject was discontinued from the study or the study was terminated. Dose reductions could be made at any time for safety reasons. Incremental dose increases were also allowed during the Treatment Period at the discretion of the Investigator (as clinically indicated) and according to the stepwise titration scheme.
Subjects were assessed for clinical worsening during each clinic visit. If clinical worsening was confirmed, the Investigator could have opted to either continue treatment with ralinepag at the current dose, increase the dose of ralinepag, interrupt treatment, or discontinue the subject at his/her discretion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of a personally signed and dated informed consent document.
- •Was willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures and was deemed an appropriate candidate for participation in a long-term extension study.
- •Female subjects were nonpregnant, nonlactating, surgically sterile or postmenopausal, or agreed to use an accepted method of birth control for at least 3 months prior to the first dose, during, and for at least 30 days after the last dose of study drug.
- •Male subjects were either surgically sterile or agreed to use a condom with spermicide when sexually active with a female partner who was not using an acceptable method of birth control during the study and for 30 days after the last dose of study drug.
- •Male and female subjects agreed not to participate in a conception process during the study and for 30 days after the last dose of study drug.
- •Fulfilled all eligibility criteria for Study APD811-003 and completed the study as planned.
- •Subjects who were assigned to placebo in Study APD811-003 and experienced clinical worsening in that study could enroll in Study APD811-007 after completing all end of study procedures per protocol, including RHC, for Study APD811-003 and had their data locked.
排除标准
- •Subjects who enrolled in Study APD811-003 and were withdrawn from study drug treatment due to any adverse event (AE), serious adverse event (SAE), or subjects who did not complete Study APD811003, with the exception made for placebo-treated subjects who experienced a clinical worsening event.
- •Female •subjects who wished to become pregnant.
- •Systolic blood pressure <90 mmHg at Baseline.
- •Other severe acute or chronic medical or laboratory abnormalities that could have increased the risk associated with study participation or investigational product administration or interfered with the interpretation of study results and, in the judgment of the investigator, would have made the subject inappropriate for entry into this study.
研究组 & 干预措施
Oral Ralinepag
Ralinepag immediate-release (IR) capsules of 10, 20, 30, 40, and 100 mcg or extended-release (XR) tablets of 50, 250, and 400 mcg for oral administration.
干预措施: Ralinepag (Drug)
结局指标
主要结局
Change From Baseline in Pulmonary Vascular Resistance
时间窗: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.
Pulmonary vascular resistance was collected by right heart catheterization (RHC).
Change From Baseline in Cardiac Output
时间窗: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.
Cardiac output was collected by right heart catheterization (RHC).
Change From Baseline in Mean Pulmonary Arterial Pressure
时间窗: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.
Mean pulmonary arterial pressure was collected by right heart catheterization (RHC).
Change From Baseline in Cardiac Index
时间窗: At 1 or 2 years after the subject enrolled into the study, pending their last RHC prior to Protocol Amendment 2.
Cardiac index was collected by right heart catheterization (RHC).
次要结局
- Time From Randomization to the First Protocol-defined Clinical Worsening Event(From Baseline to 28 days following discontinuation of study drug, up to 235 weeks.)
- Change From Baseline in 6MWD(From Baseline to discontinuation of study drug, up to 235 weeks)
- Change From Baseline in WHO/NYHA FC(From Baseline to 28 days following discontinuation of study drug, up to 235 weeks)