An Open-Label Extension Study to Assess the Safety, Tolerability, and Effectiveness of the Long-Term Use of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 91
- 试验地点
- 60
- 主要终点
- Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity
研究概览
简要总结
The primary purpose of the study is to evaluate the safety and tolerability of the long-term use of TPIP in participants with PAH from studies INS1009-201 (NCT04791514), INS1009-202 (NCT05147805) and other lead-in studies of TPIP in participants with PAH.
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
- •Male and female participants who completed end of treatment study visit in Study INS1009-201, INS1009-202, or any other lead-in PAH TPIP study. Participants for whom the OLE study was not available at the time of their completion of the lead-in study are eligible for enrolment within one year of their lead-in end of treatment visit.
- •Complete baseline screening assessments to confirm eligibility to participate if more than 30 days have elapsed since the end of the study visit in Study INS1009-201, INS1009-202, or any other lead-in PAH TPIP study.
排除标准
- •Initiation of parenteral administration of prostacyclin analogues (eg, TRE, epoprostenol) since the completion of studies INS1009-201, INS1009-202 or other TPIP studies. Initiation of inhaled prostacyclin analogues (eg, TRE [Tyvaso] or iloprost) and oral prostacyclin analogues (eg, TRE [Orenitram]) or receptor agonists (eg, selexipag) are permitted if stopped 24 hours prior to the start of study drug administration.
- •Any new ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any new symptomatic bradycardia.
- •New-onset of heart disease including left ventricular ejection fraction (LVEF) ≤40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heart disease (eg, stable angina, myocardial infarction, etc).
- •New evidence of thromboembolic disease as assessed by ventilation/perfusion (VQ) scan, pulmonary angiography, or pulmonary computed tomography (CT) scan.
- •Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-
- •Interval organ transplantation.
- •New active liver disease or hepatic dysfunction.
- •Interval malignancy with exception of completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
- •Use of any investigational drug/device or participation in any investigational study within 30 days prior to screening, not including TPIP of the lead-in study.
- •Current use of cigarettes (as defined by Centers for Disease Control and Prevention [CDC]) or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime, who smokes either every day or some days.
- •Participants who currently inhale marijuana (recreational or medical).
- •Note: Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Treprostinil Palmitil Inhalation Powder (TPIP)
Participants who are not transitioning immediately from other TPIP studies:INS1009-201(NCT04791514), INS1009-202(NCT05147805) and other lead-in studies, will be given TPIP, once daily (QD), starting with 80 micrograms (μg), up-titrated to highest tolerated dose between 80 μg and 640 μg during 3-week titration period that maybe increased upto maximum dose of 1280 μg QD post initial titration, per investigator's assessment. Overall treatment period=24 months.
Participants transitioning immediately from randomized blinded lead-in TPIP study and who previously received:
- TPIP- will be given placebo QD(80 μg upto achieved TPIP dose from previous study)along with achieved TPIP dose from previous study in blinded manner during 3-week titration period.
- Placebo- will be given TPIP QD (80 μg up to achieved placebo dose from previous study)along with achieved placebo dose from previous study in blinded manner during 3-week titration period.Overall treatment period=24 months.
干预措施: Treprostinil Palmitil (Drug)
Treprostinil Palmitil Inhalation Powder (TPIP)
Participants who are not transitioning immediately from other TPIP studies:INS1009-201(NCT04791514), INS1009-202(NCT05147805) and other lead-in studies, will be given TPIP, once daily (QD), starting with 80 micrograms (μg), up-titrated to highest tolerated dose between 80 μg and 640 μg during 3-week titration period that maybe increased upto maximum dose of 1280 μg QD post initial titration, per investigator's assessment. Overall treatment period=24 months.
Participants transitioning immediately from randomized blinded lead-in TPIP study and who previously received:
- TPIP- will be given placebo QD(80 μg upto achieved TPIP dose from previous study)along with achieved TPIP dose from previous study in blinded manner during 3-week titration period.
- Placebo- will be given TPIP QD (80 μg up to achieved placebo dose from previous study)along with achieved placebo dose from previous study in blinded manner during 3-week titration period.Overall treatment period=24 months.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity
时间窗: From screening up to last follow up visit (Up to approximately 26 months)
次要结局
- Change From Pre-OLE Baseline in the Concentration of N-Terminal Fragment B-Type Natriuretic Peptide (NT-proBNP) in Blood(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Change From Pre-OLE Baseline in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 Score(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Change From Pre-OLE Baseline in New York Heart Association/ World Health Organization (NYHA/WHO) Functional Capacity Class(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Annualized Clinical Worsening Event Rate(OLE Baseline (Day 1) up to Month 24 or early discontinuation)
- Absolute Change From Pre-Open Label Extension (OLE) Baseline in 6-Minute Walk Distance (6MWD)(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Relative Change From Pre-OLE Baseline in 6MWD(Pre-OLE baseline (baseline of the lead-in TPIP study), Months 6, 12, 18, and 24)
- Plasma Concentration Levels of Treprostinil Palmitil (TP) and Treprostinil (TRE)(OLE Baseline (Day 1), Months 6, 12, 18, and 24)