A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 383
- 试验地点
- 22
- 主要终点
- Frequently Reported (15% or More Overall) Adverse Events by Severity
研究概览
简要总结
AMB-320/321-E was designed to provide long-term, controlled monitoring of pulmonary arterial hypertension (PAH) patients treated with ambrisentan (AMB) in order to properly define the adverse event profile associated with this endothelin receptor antagonist (ERA), including the incidence and severity of elevated serum liver function tests (LFTs). In addition, this study continued the efficacy assessments of the previous studies, examined long-term AMB treatment success, and compared long-term survival of subjects treated with AMB to the NIH registry of patients with PAH.
详细描述
AMB-320 (ARIES-1; NCT00423748) and AMB-321 (ARIES-2; NCT00423202) were 12-week, Phase 3, randomized, double-blind, placebo-controlled, multicenter, efficacy studies of AMB in subjects with PAH. The objectives of these studies were to determine the effect of three doses of AMB (2.5, 5.0, and 10.0 mg) on exercise capacity, as well as several clinical measures of PAH. The current study (NCT00578786) was unblinded (by design) prior to completion. The ARIES studies were identical except for the dose groups assessed and the geographic locations where the studies were conducted. Both studies evaluated placebo and 5.0-mg AMB dose groups; however, AMB-320 (NCT00423748) also examined an AMB dose of 10.0 mg, while AMB-321 (NCT00423202) included an AMB dose of 2.5 mg. AMB-320/321-E was an optional study for subjects who had participated in AMB-320 (NCT00423748) or AMB-321 (NCT00423202) that allowed continued long-term treatment with AMB.
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
- Triple (Participant, 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
- •Subject must have completed Week 12 of AMB-320 (NCT00423748) or AMB-321 (NCT00423202) or must have received placebo during AMB-320 (NCT00423748) or AMB-321 (NCT00423202) and met two or more early escape criteria;
- •Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form and must sign the form prior to the initiation of any study procedures.
- •Female subject of childbearing potential must agree to use two reliable methods of contraception until study completion and for at least four weeks following their final study visit. Reliable methods include: birth control pills/implants/injections, intrauterine devices (IUDs), spermicide, diaphragms, or condoms.
排除标准
- •Subjects must have met the exclusion criteria of the AMB-320 (NCT00423748) and AMB-321 (NCT00423202)studies. In addition, a subject who meets any one of the following criteria is ineligible for participation in the study:
- •Subject receiving bosentan, sildenafil, or iv inotropes at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit;
- •Subject receiving chronic prostanoid therapy (epoprostenol, treprostinil, iloprost, beraprost, or any other investigational prostacyclin derivative) within four weeks prior to the AMB-320/321-E Screening/RandomizationVisit;
- •Female subject who is pregnant or breastfeeding;
- •Subject with cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject;
- •Subject who has demonstrated noncompliance with previous medical regimens;
- •Subject who has a recent history of abusing alcohol or illicit drugs;
- •Subject who has participated in a clinical study involving another investigational drug or device at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit.
研究组 & 干预措施
Ambrisentan
2.5, 5 or 10 mg ambrisentan
干预措施: ambrisentan (Drug)
结局指标
主要结局
Frequently Reported (15% or More Overall) Adverse Events by Severity
时间窗: Baseline to Week 295
The primary endpoint of this study is the incidence and severity of adverse events associated with long-term exposure to AMB in participants with PAH. The most frequently occurring adverse events (occurring in 15% or more of the participants in the combined group) are presented, by severity, that began after entering this extension study. Adverse events that were serious are included. Adverse events are coded according to the Medical Dictionary for Regulatory Activities (MedDRA) Version 6.1 and are presented by MedDRA preferred term. Severity was graded as follows: mild (AE did not interfere with routine activities; subject may have experienced slight discomfort), moderate (AE interfered with routine activities; subject may have experienced significant discomfort), and severe (AE made it impossible to perform routine activities; subject may have experienced intolerable discomfort or pain).
Serum Aminotransferases Relative to the Upper Limit of the Normal Range (ULN)
时间窗: Baseline to Week 295
The number of participants with serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) falling into the following categories: \>3.0 and \</= 5.0 x ULN, \>5.0 and \</= 8.0 x ULN, and \>8.0 x ULN. Includes the highest value per participant across all visits as well as values from early termination visits.
次要结局
- Baseline Exercise Capacity as Measured by the 6-Minute Walk Distance Test(Baseline)
- Change From Baseline to Week 24 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test(Baseline to Week 24)
- Change From Baseline to Week 48 (Year 1) in Exercise Capacity as Measured by the 6-Minute Walk Distance Test(Baseline to Week 48)
- Change From Baseline to Year 2 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test(Baseline to Year 2)
- Change From Baseline to Year 3 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test(Baseline to Year 3)
- Baseline Borg Dyspnea Index(Baseline)
- Change From Baseline to Year 1 in Borg Dyspnea Index(Baseline to Year 1)
- Change From Baseline to Year 2 in Borg Dyspnea Index(Baseline to Year 2)
- Change From Baseline to Year 3 in Borg Dyspnea Index(Baseline to Year 3)
- Baseline World Health Organization (WHO) Functional Class(Baseline)
- Change From Baseline to Year 1 in World Health Organization (WHO) Functional Class(Baseline to Year 1)
- Change From Baseline to Year 2 in World Health Organization (WHO) Functional Class(Baseline to Year 2)
- Change From Baseline to Year 3 in World Health Organization (WHO) Functional Class(Baseline to Year 3)
- Baseline SF-36 Health Survey Scales for the Combined Ambrisentan Group(Baseline)
- Change From Baseline to Week 12 in SF-36 Health Survey Scales for the Combined Ambrisentan Group(Baseline to Week 12)
- Change From Baseline to Week 24 in SF-36 Health Survey Scales for the Combined Ambrisentan Group(Baseline to Week 24)
- Change From Baseline to Week 36 in SF-36 Health Survey Scales for the Combined Ambrisentan Group(Baseline to Week 36)
- Percentage of Participants With No Clinical Worsening of PAH(Baseline to Year 3)
- Percentage of Participants With Failure-Free Treatment Status(Baseline to Year 4)
- Long-term Survival(Baseline to Year 4)