A Multi-center, Open-label, Single-arm, Phase 3b Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the French, Italian and Spanish Versions of the PAH-SYMPACT™
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 160
- 试验地点
- 39
- 主要终点
- Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT
研究概览
简要总结
Prospective, multi-center, open-label, single-arm, Phase 3b psychometric validation study.
Primary objectives: To evaluate the psychometric characteristics of reliability and construct validity of the French, Italian and Spanish versions of the PAH-SYMPACT™.
To evaluate the ability of the French, Italian and Spanish versions of the PAH SYMPACT™ to detect change.
Secondary objective: To assess the safety of macitentan in patients with pulmonary arterial hypertension (PAH).
Exploratory objective: To explore the effects of macitentan on PAH symptoms and their impact (as measured by the PAH-SYMPACT™) in patients with PAH in France, Italy and Spain.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to initiation of any study-mandated procedure.
- •Patients with symptomatic PAH in WHO Functional Class (FC) II or III.
- •Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:
- •Idiopathic, or,
- •Heritable, or,
- •Drug or toxin induced, or,
- •Associated with one of the following:
- •i. Connective tissue disease, ii. Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, iii. HIV infection.
- •Documented hemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to Screening showing:
- •Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and,
- •Resting pulmonary vascular resitance (PVR) > 240 dyn.s.cm-5 and,
- •Pulmonary capillary wede pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg.
- •6-minute walk distance (6MWD) ≥ 150 m at Screening.
- •Able to fluently speak and read the local language.
- •Men or women aged 18-80; women of childbearing potential (as defined below) must:
- •Have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly serum pregnancy tests, and,
- •Agree to use two reliable methods of contraception in parallel, from Screening Visit 1 until 1 month after study drug discontinuation (see details below).
- •A female is considered to have childbearing potential unless she meets at least one of the following criteria:
- •Previous bilateral salpingo and/or oophorectomy, or hysterectomy.
- •Premature ovarian failure confirmed by a specialist.
- •Pre-pubescence, XY genotype, Turner syndrome, uterine agenesis.
- •Postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause.
- •Of the two contraceptive methods that must be used, one must be from Group 1, and one must be from Group 2, defined as follows:
- •Group 1: Oral, implantable, transdermal or injectable hormonal contraceptives, intrauterine devices, female sterilization (tubal ligation or non surgical sterilization, e.g., permanent contraception with Essure procedure), or partner's sterilization (vasectomy). If a hormonal contraceptive is chosen from this group, it must be taken for at least 1 month prior to enrollment. Alternatively, if the Essure procedure is chosen as a contraceptive method, a hysterosalpingogram must have been performed to confirm correct location of the microinserts and tubal occlusion (as per manufacturer's recommendations).
- •Group 2: Female or male condoms, diaphragm or cervical cap, any of them in combination with a spermicide.
- •Sexual abstinence, rhythm methods, or contraception by the partner alone are not considered as acceptable methods of contraception for this study.
排除标准
- •Known moderate-to-severe obstructive lung disease (i.e., forced expiratory volume in one second [FEV1] < 80 % of predicted, with FEV1 / forced vital capacity [FVC] < 70%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
- •Known moderate-to-severe restrictive lung disease (i.e., total lung capacity [TLC] < 60% of predicted value).
- •Hemoglobin < 100g/L at Screening.
- •Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 X upper limit of the normal range (ULN) at Screening.
- •Patients undergoing dialysis.
- •Systolic blood pressure (SBP) < 90 mmHg at Screening.
- •Body weight < 40 kg at Screening.
- •Known concomitant life-threatening diseases with a life expectancy of < 12 months.
- •Treatment with ERAs within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial.
- •Treatment with intravenous or subcutaneous prostacyclin or prostacyclin analogs within 3 months prior to Visit 2, or scheduled to receive any of these compounds during the trial.
- •Treatment with soluble guanylate cyclase stimulator (riociguat) within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial.
- •Patients who changed the dose of or discontinued phosphodiesterase type-5 inhibitor (PDE5i), inhaled prostacyclin analogues, or calcium channel blockers within 3 months prior to Visit
- •Initiation of diuretics within 1 week prior to the Baseline period.
- •Patients on oral diuretics in whom the dose has not been stable for at least 1 week prior to the Baseline period.
- •Treatment with cytochrome P4500 (CYP) 3A inducers within 4 weeks prior to Visit
- •Recently started (< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise.
- •Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study.
- •Known hypersensitivity to macitentan or its excipients or drugs of the same class.
- •Treatment with another investigational drug within 3 months prior to Visit
- •Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
研究组 & 干预措施
Macitentan
Macitentan tablet, dose of 10 mg, once daily
干预措施: Macitentan (Drug)
结局指标
主要结局
Evaluation of the Reliability and the Construct Validity of the Cardiopulmonary Symptoms Domain of the PAH-SYMPACT
时间窗: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms".The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
Evaluation of the Reliability and the Construct Validity of the Cardiovascular Symptoms Domain of the PAH-SYMPACT
时间窗: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
The Cardiovascular Symptoms domain consists of 5 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT was administered daily over a 7 day period. The recall period of symptom items is the last 24 hours. An average Cardiovascular Symptoms domain score is determined based on the daily scores of the 5 items. It was administered two times (daily during 7 days each time) prior to administration of Macitentan (Visit 2, Baseline) and daily during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
Evaluation of the Reliability and the Construct Validity of the Cognitive/Emotional Impacts Domain of the PAH-SYMPACT
时间窗: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
The Cognitive/Emotional Impacts domain consists of 4 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "not at all"/"with no difficulty at all" and value 4 corresponds to "very much"/"extremely"/ "not able at all". The impacts part of the PAH-SYMACT was administered on Day 7 of the symptoms part administration. Items in the impact part have a 7 day recall period. An average Cognitive/Emotional Impacts domain score is determined based on the 4 items in the domain. It was administered two times prior to administration of Macitentan (Visit 2, Baseline) and during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16)."
Evaluation of the Reliability and the Construct Validity of the Physical Impacts Domain of the PAH-SYMPACT
时间窗: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16)
The Physical Impacts domain consists of 7 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "not at all"/"with no difficulty at all" and value 4 corresponds to "very much"/"extremely"/ "not able at all". The impacts part of the PAH-SYMACT was administered on Day 7 of the symptoms part administration. Items in the impact part have a 7 day recall period. An average Physical Impacts domain score is determined based on the 7 items in the domain. It was administered two times prior to administration of Macitentan (Visit 2, Baseline) and during the 7-day period in the treatment period prior to Visit 3 (Week 8) and Visit 4 (Week 16).
次要结局
未报告次要终点