A Multi-center, Open-label, Single-arm, Phase 3b Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the PAH-SYMPACT Instrument
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 284
- 试验地点
- 80
- 主要终点
- Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT)
研究概览
简要总结
SYMPHONY is prospective, multi-center, open-label, single-arm, Phase 3b psychometric validation study of the PAH-SYMPACT, a new quality of life questionnaire for patients with pulmonary arterial hypertension. Patients will be in the study for 5 1/2 months, 4 months of which they will receive macitentan, 10 mg, once daily.
The primary objectives are to demonstrate the final content validity of the PAH SYMPACT instrument, to demonstrate the psychometric characteristics of reliability and construct validity of the PAH-SYMPACT instrument, and to demonstrate the ability of the PAH SYMPACT instrument to detect change. The secondary objective is to assess the safety of macitentan in patients with pulmonary arterial hypertension. The exploratory objective is to explore the effects of macitentan on PAH symptoms and their impact (as measured by the PAH-SYMPACT) in patients with pulmonary arterial hypertension.
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 —（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 World Health Organization (WHO) Functional Class (FC) II to IV
- •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 one 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 resistance (PVR) > 240 dyn•s•cm-5 and
- •Pulmonary capillary wedge 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 English
- •For patients on phosphodiesterase type-5 inhibitors (PDE5i), inhaled prostacyclin analogues, or calcium channel blockers, stable doses for at least 3 months prior to Visit 2
- •For patients on oral diuretics, stable doses for at least 4 weeks prior to Visit 2
- •Men or women aged 18 or older
- •A woman is considered to be of childbearing potential unless she:
- •Has not yet entered puberty, or
- •Does not have a uterus, or
- •Has gone through menopause (has not had a period for at least 12 months for natural reasons, or who has had their ovaries removed)
- •A women of childbearing potential is eligible only if she meets both criteria below:
- •Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
- •Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation
排除标准
- •Moderate to severe obstructive lung disease: forced expiratory volume in one second (FEV1) / forced vital capacity < 70% and FEV1 < 65% of predicted value after bronchodilator administration
- •Moderate to severe restrictive lung disease: total lung capacity < 60% of predicted value
- •Hemoglobin < 75% of the lower limit of the normal range at screening
- •Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN) at screening
- •Estimated creatinine clearance < 30 mL/min at screening
- •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
- •Any condition that prevents compliance with the protocol or adherence to therapy
- •Treatment with endothelin receptor antagonists (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 riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
- •Treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors within 4 weeks prior to Visit 2
- •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 2
- •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
Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT)
时间窗: From Screening Visit (Day -14) to End of Treatment (EOT) Visit (Visit 4, Week 16)
Content validity of the PAH-SYMPACT was assessed using item performance, exploratory and confirmatory factor analysis. The final item content and domain structure of PAH-SYMPACT was determined based on these analyses from the Steering Committee (expert clinicians) and findings from the qualitative research done with patients previously.
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability.
时间窗: From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.
The reliability of the PAH-SYMPACT is assessed by internal consistency reliability. This was determined using Cronbach's alpha-a value on an internal level scale from 0 to 1.0 with higher scores indicating a more-reliable (precise) instrument.
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability.
时间窗: From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.
The reliability of the PAH-SYMPACT is assessed by test-retest reliability. Intra-class correlation coefficients (ICCs) assess test-retest reliability for the symptom and impact part scores as well as domains. ICCs equal to or greater than 0.70 are considered to demonstrate good test-retest reliability for total and domain scores.
次要结局
- Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits)(From Day 1 (Baseline Visit) to End of Study visit (EoS).)