Multicenter, Open-label, Single-group Study to Assess the Tolerability and the Safety of the Transition From Inhaled Treprostinil to Oral Selexipag in Adult Patients With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 34
- 试验地点
- 15
- 主要终点
- Time to Discontinuation of Inhaled Treprostinil.
研究概览
简要总结
This study enrolls patients with pulmonary arterial hypertension (PAH) treated with inhaled treprostinil. During the study, the treatment with inhaled treprostinil will be tapered off and simultaneously replaced with an oral treatment (selexipag) targeting the disease in a similar way. The purpose of the study is i) to investigate the safety and tolerability of oral selexipag in patients who transition from inhaled treprostinil, ii) to investigate the effects of oral selexipag on PAH severity and exercise ability before and after transition, and iii) to gain new information about the patients experience taking oral selexipag compared to inhaled treprostinil. Study participants may stay in the study until the FDA has granted marketing authorization.
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
- •Male and female patients aged from 18 to 75 years (inclusive) with pulmonary arterial hypertension (PAH).
- •Etiology of PAH belonging to one of the following subgroups: idiopathic PAH, Heritable PAH, drug or toxin induced, associated with connective tissue disease, associated with HIV infection, associated with congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair.
- •Women of childbearing potential are eligible only if the following apply: Negative serum pregnancy test at Visit 1 and a negative urine pregnancy test at Visit on Day 1, agreement to undertake monthly urine pregnancy tests during the study and up to 30 days after study drug discontinuation, agreement to use efficient methods of birth control from Visit 1 up to at least 30 days after study treatment discontinuation.
- •Documented hemodynamic diagnosis of PAH by right heart catheterization (RHC).
- •Inhaled treprostinil treatment ongoing for at least 90 days and at stable dose for at least 30 days prior to Day
- •WHO functional class (FC) II or III at Visit 1 and Visit
- •6-minute walk distance (6MWD) ≥ 300 m at Visit
- •On background oral PAH therapy for at least 90 days and on a stable dose for 30 days prior to Visit
- •Acceptable concomitant PAH therapies are one or two of the following: a) Endothelin receptor antagonist (ERA), b) Phosphodiesterase type 5 (PDE-5) inhibitor or soluble guanylate cyclase (sGC) stimulator.
排除标准
- •Treatment with any prostacyclin or prostacyclin analogs other than inhaled treprostinil within 90 days before Day 1, or patients scheduled to receive any of these treatments within the duration of the study.
- •Any hospitalization within 90 days before Day
- •Worsening in WHO FC within 30 days prior to Day
- •At any time prior to Day 1, documented moderate or severe obstructive or restrictive lung disease.
- •Known or suspicion of pulmonary veno-occlusive disease (PVOD).
- •Anemia: < 80 g/L (5.0 mmol/L) hemoglobin.
- •Clinically relevant thyroid disease (hypo- or hyperthyroidism).
- •Known and documented severe hepatic impairment.
- •Uncontrolled hypertension.
- •Sitting systolic blood pressure < 85 mmHg.
- •Acute myocardial infarction within the last 90 days prior to Visit
- •History of left-sided heart disease.
- •Left ventricular disease/dysfunction risk factors.
- •Documented pericardial effusion within 90 days prior to Visit
- •Documented severe renal insufficiency.
- •Receiving or having received any investigational drugs within 90 days before Day
- •Having received selexipag at any time before Day
- •Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements.
- •Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training during the study.
- •Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
- •Known concomitant life-threatening disease with a life expectancy < 12 months.
- •Females who are lactating or pregnant or plan to become pregnant during the study.
- •Known hypersensitivity to any of the excipients of the drug formulation.
研究组 & 干预措施
Selexipag, Open Label
Subjects on inhaled treprostinil treatment participate in a 16-week main treatment period including down-titration of treprostinil to end of Week 8 and parallel up-titration of selexipag to the maximum tolerated dose (MTD) up to Week 12, for each individual patient but not above 1600 mcg twice daily.
From Week 12 up to Week 16, patients continue selexipag at their individual MTD. Patients could continue the study drug selexipag during the extended treatment period from Week 16 until commercial availability of selexipag.
干预措施: Selexipag (Drug)
结局指标
主要结局
Time to Discontinuation of Inhaled Treprostinil.
时间窗: Baseline to Week 16
Median time from baseline (Day1) to the end of down-titration of inhaled treprostinil is calculated
Percentage of Subjects With Sustained Treatment Transition
时间窗: At Week 16
A sustained treatment transition is considered if the 3 following criteria are met a) being on study treatment (selexipag) at Week 16, and b) not having a study treatment interruption(s) of a total of 8 days or more prior to Week 16, and c) absence of inhaled treprostinil or any prostanoid treatment after Week 8 up to Week 16. The percentage of subjects with a sustained treatment transition is calculated with 95% confidence interval (CI) using the Clopper-Pearson method.
Number of Subjects With Adverse Events Leading to Premature Discontinuation of Selexipag
时间窗: Up to 22 weeks on average
Number of subjects with adverse events leading to premature discontinuation of selexipag is determined from the first dose of selexipag up to the last dose of selexipag
Absolute Change From Baseline Over Time in Heart Rate (HR)
时间窗: Baseline, Week 4, Week 12, Week 16
Pulse rate is measured after at least 5 minutes of rest in a sitting position. Median change from baseline to pre-specified post-baseline visits are calculated.
Maximal Tolerated Dose
时间窗: At Week 12, in subjects still on selexipag at Week 16
This is the individual maximal tolerated dose (MTD) observed at Week 12 in the subjects still on selexipag at Week 16. MTD is defined as the dose of selexipag reached with the last dose change up to Week 12
Percentage of Subjects With Treatment-emergent Adverse Events (AEs),
时间窗: 26 weeks on average (from the first dose of selexipag up to 30 days after the last dose of selexipag)
Percentage of subjects with treatment-emergent AEs (serious and non serious), regardless of relationship to selexipag
Absolute Change From Baseline Over Time in Blood Pressure
时间窗: Baseline, Week 4, Week 12, Week 16
Both systolic(SBP) and diastolic (DBP) arterial blood pressure were measured in a sitting position after at least 5 minutes of rest at scheduled time points. Median change from baseline to pre-specified post-baseline visits are calculated
次要结局
- Percentage of Subjects With WHO Functional Class (FC) Change From Baseline(Baseline and Week 16)
- Absolute Change in 6-minute Walk Distance (6MWD) at Trough(Baseline and Week 16)
- Geometric Mean of the Ratio in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) of Week 16 to Baseline(Baseline and Week 16)
- Percentage of Patients With Change in 6-minute Walk Distance (6MWD)(Baseline and Week 16)