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

NCT ID: NCT05147805

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-24
• Study Completion Date: 2025-03-27

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.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treprostinil Palmitil Inhalation Powder

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.

Group Type: EXPERIMENTAL

Treprostinil Palmitil

Intervention Type: DRUG

Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.

Placebo

Participants will be administered a placebo matching TPIP once per day for 16 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.

Interventions

Treprostinil Palmitil

Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.

Intervention Type: DRUG

Placebo

Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler.

Intervention Type: DRUG

Other Intervention Names

INS1009

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insmed Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

USA010

Winter Park, 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

USA017

New York, New York, United States

USA016

Dallas, Texas, United States

USA012

Denison, Texas, United States

USA018

Houston, Texas, United States

ARG009

Quilmes, Buenos Aires, Argentina

ARG002

Rosario, Santa Fe Province, Argentina

ARG006

Rosario, Santa Fe Province, Argentina

ARG007

San Miguel de Tucumán, Tucumán Province, Argentina

ARG004

Córdoba, , Argentina

ARG001

Córdoba, , Argentina

ARG008

Cuiudad Autónoma de Buenos Aires, , Argentina

AUS005

New Lambton Heights, New South Wales, Australia

AUS004

Milton, Queensland, Australia

AUS001

Woolloongabba, Queensland, Australia

AUS003

Adelaide, South Australia, Australia

AUS002

Hobart, Tasmania, Australia

AUT002

Linz, Upper Austria, Austria

AUT001

Vienna, , Austria

BEL003

Anderlecht, Brussels Capital, 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-Wurttemberg, Germany

GER006

Dresden, Saxony, Germany

GER001

Halle, Saxony-Anhalt, Germany

GER002

Lübeck, Schleswig-Holstein, Germany

GER007

Berlin, , Germany

GER003

Munich, , Germany

ITA003

Napoli, Campania, Italy

ITA006

Milan, Lombardy, Italy

ITA005

Monza, Lombardy, Italy

ITA002

Pavia, Lombardy, Italy

ITA001

Palermo, Sicily, Italy

ITA004

Roma, , Italy

JPN005

Sapporo, Hokkaidô, Japan

JPN004

Sapporo, Hokkaidô, Japan

JPN007

Kurume-Shi, Hukuoka, Japan

JPN006

Tsukuba, Ibaraki, Japan

JPN001

Kagoshima, Kagoshima-ken, Japan

JPN009

Nagasaki, Nagasaki, Japan

JPN002

Okayama, Okayama-ken, Japan

JPN008

Shinjuku-Ku, Tokyo, Japan

JPN003

Suita-Shi, Ôsaka, Japan

MYS005

Alor Star, Kedah, Malaysia

MYS002

Kuantan, Pahang, Malaysia

MYS003

Kajang, Selangor, Malaysia

MYS004

Sungai Buloh, Selangor, Malaysia

MEX005

Lomas de Guevara, Jalisco, Mexico

MEX003

Mexico City, Mexico City, Mexico

MEX004

San Luis Potosí City, , Mexico

MEX001

Sertoma, , Mexico

PHL001

Quezon City, National Capital Region, Philippines

PHL002

Makati City, , Philippines

SRB004

Belgrade, Belgrade, Serbia

SRB001

Belgrade, , Serbia

SRB003

Belgrade, , Serbia

ESP006

Palma de Mallorca, Balearic Islands, Spain

ESP001

Santander, Cantabria, Spain

ESP002

Barcelona, , Spain

ESP007

Las Palmas, , Spain

ESP008

Madrid, , Spain

ESP003

Seville, , Spain

ESP004

Toledo, , Spain

CHE002

Lausanne, Vaud (fr), Switzerland

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

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Denmark; Germany; Italy; Japan; Malaysia; Mexico; Philippines; Serbia; Spain; Switzerland; United Kingdom

Other Identifiers

2021-001528-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505541-99-00

Identifier Type: OTHER

Identifier Source: secondary_id

INS1009-202

Identifier Type: -

Identifier Source: org_study_id