A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension

Phase 2

Active, not recruiting

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Treprostinil Palmitil; Drug: Placebo

• Registration Number: NCT05147805
• Lead Sponsor: Insmed Incorporated

Brief Summary

The main objective of the study is to assess the effect of treprostinil palmitil inhalation powder (TPIP) compared with placebo on pulmonary vascular resistance.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-24
• Study First Submitted QC: 2021-11-24
• Study First Posted: 2021-12-07
• Study Start: 2022-08-24
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2025-07-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

• Participants must be ≥ 18 to ≤ 75 years at the time of signing the informed consent form (ICF).

• Participants must have a diagnosis of World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH) [pulmonary arterial hypertension (PAH)] in any of the following subtypes:

  1. Idiopathic
  2. Heritable
  3. Drug/toxin-induced or connective tissue disease (CTD)-associated PAH
  4. Congenital heart disease-related with simple systemic-to-pulmonary shunt at least 1 year following repair.

• PAH diagnosis for at least 3 months.

• Participants must be on stable PH therapy consisting of up to 2 medications from the following classes:

  1. Endothelin receptor antagonists (eg, ambrisentan, bosentan, macitentan)
  2. Phosphoesterase type 5 inhibitors (eg, sildenafil, tadalafil)
  3. Guanylate cyclase stimulator (eg, riociguat)

• No change in PH medications (eg, ambrisentan, bosentan, macitentan, sildenafil, tadalafil, riociguat) or dosage for at least 30 days prior to Screening.

• No change in long-term diuretic use or dosage for at least 30 days prior to Screening.

• Body Mass Index (BMI) within the range 18.0-37.0 kg/m^2 (inclusive).

• Male participants: Male participants who are not sterile and have female partners of childbearing potential, must be using effective contraception from Day 1 to at least 90 days after the last dose of study drug.

• Female participants: Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, (ie, post-tubal ligation for at least 12 months) or using highly effective contraception methods (ie, methods that alone or in combination achieve <1% unintended pregnancy rates per year when used consistently and correctly) from Day 1 to at least 90 days after the last dose of study drug.

• Male participants with pregnant or non-pregnant woman of childbearing potential partner must use a condom in order to avoid potential exposure to embryo/fetus.

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.

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Exclusion Criteria

• History of PH other than idiopathic, hereditary, drug/toxin-induced, repaired simple congenital heart disease, or CTD-associated PAH (eg, complex, congenital heart disease-associated PAH, portal hypertension-associated PAH, PH belonging to Groups 2 through 5).
• Allergy, or documented hypersensitivity or contraindication, to TPIP or Treprostinil or mannitol (an excipient of the TPIP formulation).
• Any known ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any symptomatic bradycardia.
• History 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).
• Participation in a cardio-pulmonary rehabilitation program within 1 month of Screening Visit.
• Evidence of thromboembolic disease as assessed by ventilation-perfusion (VQ) scan, pulmonary angiography, or pulmonary computed tomography (CT) scan.
• Active liver disease or hepatic dysfunction.
• History of HIV infection.
• Established diagnosis of hepatitis B viral infection, or positive for hepatitis B surface antigen (HBsAg) at the time of Screening.
• Established diagnosis of hepatitis C viral infection at the time of screening.
• Active and current symptomatic coronavirus disease 2019 (COVID-19) or previous severe disease and/or hospitalization due to COVID-19.
• Use of live attenuated vaccines within 30 days of the Screening Visit.
• Participants with Down's Syndrome.
• History of abnormal bleeding or bruising.
• History of solid organ transplantation.
• Known or suspected immunodeficiency disorder, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immune compromised status, as judged by the Investigator.
• History of alcohol or drug abuse within 6 months prior to Screening.
• Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6-minute walk test (eg, angina pectoris, claudication, musculoskeletal disorder, need for walking aids).
• Participants with current or recent (past 30 days) lower respiratory tract infection.
• History of malignancy in the past 5 years, with exception of completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
• Change in PH medication (endothelin receptor agonists, phosphoesterase type 5 inhibitors, and guanylate cyclase stimulators or diuretics) between Screening and Baseline.
• Have participated in any other interventional clinical studies within 30 days prior to Screening.
• Current use of cigarettes (as defined by Centers for Disease Control and Prevention) or e-cigarettes.
• Participants who currently inhale marijuana (recreational or medical).
• Pregnant or breastfeeding.

Note: Other inclusion/exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treprostinil Palmitil Inhalation Powder	Treprostinil Palmitil	Participants will be administered TPIP once per day at a starting dose of 80 micrograms (μg). Participants will be up-titrated to the highest tolerated dose for each individual participant of between 80 μg and 640 μg during the initial 3 weeks of treatment. The overall treatment period will be 16 weeks.
Placebo	Placebo	Participants will be administered a placebo matching TPIP once per day for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Pulmonary Vascular Resistance at Week 16	Baseline to Week 16

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16	Baseline and Week 5, Week 10 and Week 16
Percent Change from Baseline in 6-Minute Walk Test Distance at Week 5, Week 10 and Week 16	Baseline and Week 5, Week 10 and Week 16
Number of Participants Who Experience a Treatment-emergent Adverse Event (AE)	Day 1 up to Week 20
Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Evaluations	Baseline to Week 16
Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurements	Baseline to Week 16
Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements	Baseline to Week 16
Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Time to Maximum Plasma Concentration (Tmax) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Area Under the Concentration-time Curve from Time 0 to 24 Hours Post-Dose (AUC24) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Area Under the Concentration-time Curve from Time 0 to Infinity (AUC∞) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Area Under the Concentration-time Curve from Time 0 to Infinity (AUC∞) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Area Under the Concentration-time Curve from Time 0 to Last Measurable Concentration (AUClast) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Elimination Half-Life (t1/2) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Number of Participants Who Experience a Clinically Significant Change from Baseline in Physical Examinations	Baseline to Week 16
Change from Baseline in the Concentration of N-Terminal-Pro Hormone Brain Natriuretic Peptide (NT-proBNP) Levels at Week 5, Week 10 and Week 16	Baseline and Week 5, Week 10 and Week 16 or end of study
Maximum Plasma Concentration (Cmax) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Apparent Total Clearance (CL/F) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Apparent Total Clearance (CL/F) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Apparent Volume of Distribution After Non-Intravenous Administration (Vd/F) of Treprostinil Palmitil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose
Elimination Half-Life (t1/2) of Treprostinil	Day 1, Weeks 2, 3, 5, 10, and 16: Predose and 0.5, 1, 2 ,4 and 6 hours post-dose

Trial Locations

Locations (81)

USA025; 🇺🇸 Phoenix, Arizona, United States

USA022; 🇺🇸 Scottsdale, Arizona, United States

USA021; 🇺🇸 Tucson, Arizona, United States

USA023; 🇺🇸 Sacramento, California, United States

USA002; 🇺🇸 West Hollywood, California, United States

USA008; 🇺🇸 Gainesville, Florida, United States

USA005; 🇺🇸 Jacksonville, Florida, United States

USA007; 🇺🇸 Orlando, Florida, United States

USA011; 🇺🇸 Tampa, Florida, United States

USA009; 🇺🇸 Atlanta, Georgia, United States

USA006; 🇺🇸 Chicago, Illinois, United States

USA001; 🇺🇸 Chicago, Illinois, United States

USA013; 🇺🇸 Indianapolis, Indiana, United States

USA014; 🇺🇸 Iowa City, Iowa, United States

USA003; 🇺🇸 Kansas City, Kansas, United States

USA102; 🇺🇸 New York, New York, United States

USA016; 🇺🇸 Dallas, Texas, United States

USA018; 🇺🇸 Houston, Texas, United States

ARG009; 🇦🇷 Quilmes, Buenos Aires, Argentina

ARG006; 🇦🇷 Rosario, Santa Fe, Argentina

ARG007; 🇦🇷 San Miguel de Tucuman, Tucumán, Argentina

ARG008; 🇦🇷 Cuiudad Autónoma De Buenos Aires, Argentina

ARG001; 🇦🇷 Córdoba, Argentina

AUS001; 🇦🇺 Woolloongabba, Queensland, Australia

AUT002; 🇦🇹 Linz, Oberösterreich, Austria

AUT001; 🇦🇹 Wien, Austria

BEL003; 🇧🇪 Anderlecht, Brussels, Belgium

BEL002; 🇧🇪 Leuven, Vlaams Brabant, Belgium

BEL001; 🇧🇪 Liège, Belgium

BRA003; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

BRA004; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

BRA007; 🇧🇷 Passo Fundo, Rio Grande Do Sul, Brazil

BRA006; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

BRA002; 🇧🇷 Blumenau, Santa Catarina, Brazil

BRA001; 🇧🇷 São Paulo, Brazil

DNK001; 🇩🇰 Aarhus N, Central Jutland, Denmark

GER005; 🇩🇪 Heidelberg, Baden-Württemberg, Germany

GER006; 🇩🇪 Dresden, Sachsen, Germany

GER002; 🇩🇪 Lübeck, Schleswig-Holstein, Germany

GER007; 🇩🇪 Berlin, Germany

GER003; 🇩🇪 Munich, Germany

ITA003; 🇮🇹 Napoli, Campania, Italy

ITA006; 🇮🇹 Milano, Lombardia, Italy

ITA005; 🇮🇹 Monza, Lombardia, Italy

ITA002; 🇮🇹 Pavia, Lombardia, Italy

ITA001; 🇮🇹 Palermo, Sicilia, Italy

ITA004; 🇮🇹 Roma, Italy

JPN005; 🇯🇵 Sapporo-Shi, Hokkaidô, Japan

JPN004; 🇯🇵 Sapporo-Shi, Hokkaidô, Japan

JPN007; 🇯🇵 Kurume-Shi, Hukuoka, Japan

JPN006; 🇯🇵 Tsukuba-Shi, Ibaraki, Japan

JPN001; 🇯🇵 Kagoshima-Shi, Kagosima, Japan

JPN009; 🇯🇵 Nagasaki-Shi, Nagasaki, Japan

JPN002; 🇯🇵 Okayama-Shi, Okayama, Japan

JPN008; 🇯🇵 Shinjuku-Ku, Tokyo, Japan

JPN003; 🇯🇵 Suita-Shi, Ôsaka, Japan

MYS005; 🇲🇾 Kota Setar, Kedah, Malaysia

MYS002; 🇲🇾 Kuantan, Pahang, Malaysia

MYS003; 🇲🇾 Kajang, Selangor, Malaysia

MYS004; 🇲🇾 Sungai Buloh, Selangor, Malaysia

MEX003; 🇲🇽 Ciudad de México, Distrito Federal, Mexico

MEX005; 🇲🇽 Lomas De Guevara, Jalisco, Mexico

MEX004; 🇲🇽 San Luis Potosí, Mexico

MEX001; 🇲🇽 Sertoma, Mexico

PHL001; 🇵🇭 Quezon City, National Capital Region, Philippines

PHL002; 🇵🇭 Makati City, Philippines

SRB004; 🇷🇸 Beograd, Belgrade, Serbia

SRB001; 🇷🇸 Belgrade, Serbia

SRB003; 🇷🇸 Beograd, Serbia

ESP006; 🇪🇸 Palma de Mallorca, Baleares, Spain

ESP001; 🇪🇸 Santander, Cantabria, Spain

ESP002; 🇪🇸 Barcelona, Spain

ESP007; 🇪🇸 Las Palmas, Spain

ESP008; 🇪🇸 Madrid, Spain

ESP003; 🇪🇸 Sevilla, Spain

ESP004; 🇪🇸 Toledo, Spain

GBR001; 🇬🇧 Bath, Avon, United Kingdom

GBR002; 🇬🇧 Glasgow, Lanarkshire, United Kingdom

GBR006; 🇬🇧 London, London, City Of, United Kingdom

GBR003; 🇬🇧 Newcastle Upon Tyne, Tyne And Wear, United Kingdom

GBR004; 🇬🇧 London, United Kingdom