An Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) for Pulmonary Arterial Hypertension (PAH)
- Conditions
- Pulmonary Arterial Hypertension
- Interventions
- Drug: Placebo
- Registration Number
- NCT05649748
- Lead Sponsor
- Insmed Incorporated
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 91
- 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.
- 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-19.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treprostinil Palmitil Inhalation Powder (TPIP) Placebo 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: 1. 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. 2. 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. Treprostinil Palmitil Inhalation Powder (TPIP) Treprostinil Palmitil 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: 1. 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. 2. 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.
- Primary Outcome Measures
Name Time Method Number of Participants Who Experience at Least one Treatment Emergent Adverse Event (TEAE) and TEAEs by Severity From screening up to last follow up visit (Up to approximately 26 months)
- Secondary Outcome Measures
Name Time Method 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 Annualized clinical worsening event rate is defined as the total number of clinical worsening events that occurred during the treatment period divided by the total number of participant-years during the treatment period. Clinical worsening events are one of the following: All-cause death, or onset of TEAE with a fatal outcome occurring ≤ 14 days after study drug discontinuation; Hospitalization for right heart failure (for \> 48 hours), heart-lung or lung transplant, or atrial septostomy; Addition (or increase in dose) of specified PAH-specific medications; Combined occurrence of events including ≥20% decrease in 6MWD, worsening WHO/NYHA functional capacity class, and appearance of or worsening of signs/symptoms of right heart failure from baseline.
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
Trial Locations
- Locations (45)
GBR001
🇬🇧Bath, Avon, United Kingdom
SRB003
🇷🇸Belgrade, Serbia
ESP003
🇪🇸Sevilla, Spain
USA005
🇺🇸Jacksonville, Florida, United States
USA011
🇺🇸Tampa, Florida, United States
USA006
🇺🇸Chicago, Illinois, United States
USA001
🇺🇸Chicago, Illinois, United States
USA102
🇺🇸New York, New York, United States
USA016
🇺🇸Dallas, Texas, United States
ARG009
🇦🇷Quilmes, Buenos Aires, Argentina
ARG006
🇦🇷Rosario, Santa Fe, Argentina
ARG007
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
ARG004
🇦🇷Córdoba, Argentina
ARG001
🇦🇷Córdoba, Argentina
AUT002
🇦🇹Linz, Oberösterreich, Austria
AUT001
🇦🇹Wien, Austria
BEL003
🇧🇪Brussels, Belgium
BRA004
🇧🇷Belo Horizonte, Minas Gerais, Brazil
BRA006
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
BRA002
🇧🇷Blumenau, Santa Catarina, Brazil
DNK001
🇩🇰Aarhus, Central Jutland, Denmark
GER005
🇩🇪Heidelberg, Baden-Württemberg, Germany
GER003
🇩🇪München, Bavaria, Germany
GER002
🇩🇪Lübeck, Schleswig-Holstein, Germany
ITA002
🇮🇹Pavia, Lombardia, Italy
ITA005
🇮🇹Monza, Italy
ITA001
🇮🇹Palermo, Italy
ITA004
🇮🇹Roma, Italy
JPN005
🇯🇵Sapporo-shi, Hokkaido, Japan
JPN004
🇯🇵Sapporo, Hokkaido, Japan
JPN007
🇯🇵Kurume-shi, Hukuoka, Japan
JPN006
🇯🇵Tsukuba, Ibaraki, Japan
JPN002
🇯🇵Okayama-Shi, Okayama, Japan
JPN003
🇯🇵Suita-Shi, Osaka, Japan
MYS005
🇲🇾Alor Setar, Kedah, Malaysia
MYS002
🇲🇾Kuantan, Pahang, Malaysia
MYS004
🇲🇾Sungai Buloh, Selangor, Malaysia
MEX005
🇲🇽Lomas De Guevara, Jalisco, Mexico
MEX001
🇲🇽Monterrey, Nuevo León, Mexico
MEX003
🇲🇽Mexico City, Mexico
MEX004
🇲🇽San Luis Potosi, Mexico
PHL002
🇵🇭Makati City, Philippines
SRB001
🇷🇸Belgrade, Serbia
PHL001
🇵🇭Quezon City, National Capital Region, Philippines
ESP001
🇪🇸Santander, Spain