A Study to Evaluate the Efficacy and Safety of Once Daily Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Arterial Hypertension (PAH)

NCT07481981 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: INS1009-3012026-525265-48-00
• Study Type: interventional
• Target: 344
• Locations: 6 countries
• Sites: 26

Brief Summary

The primary objective of this study is to evaluate the effect of 24-weeks of once daily treatment with TPIP compared with placebo on exercise capacity in adults with PAH.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in 6-Minute Walk Distance (6MWD) Measured at 1 to 3 Hours Post-Dose From Baseline at Week 24

  Baseline, Week 24

Secondary Outcomes (11)

• Percentage of Participants With an Improvement From Baseline in World Health Organization (WHO) Functional Class at Week 24

  Baseline, Week 24

• Change in 6MWD Measured at 24 Hours (±2) Since the Last Dose From Baseline at Week 22

  Baseline, Week 22

• Change From Baseline in the Concentration of N-Terminal Pro Hormone Brain Natriuretic Peptide (NT-proBNP) at Week 24

  Baseline, Week 24

• Change From Baseline at Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) Physical Impacts Domain Score

  Baseline, Week 24

• Change From Baseline at Week 24 in PAH-SYMPACT Cardiopulmonary Symptoms Domain Score

  Baseline, Week 24

Study Arms (2)

Treprostinil Palmitil Inhalation Powder

EXPERIMENTAL

Participants will receive TPIP, once daily (QD), at a starting dose of 80 micrograms (μg) up to maximum tolerated dose (up to 1280 μg) for 24 weeks.

Drug: Treprostinil Palmitil Inhalation Powder

Placebo

PLACEBO COMPARATOR

Participants will receive a TPIP-matching placebo, QD, for 24 weeks.

Drug: Placebo

Interventions

Placebo DRUG

Oral inhalation using a capsule-based dry powder inhaler device.

Placebo

Treprostinil Palmitil Inhalation Powder DRUG

Oral inhalation using a capsule-based dry powder inhaler device.

Also known as: INS1009

Treprostinil Palmitil Inhalation Powder

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a diagnosis of World Health Organisation (WHO) Group 1 pulmonary hypertension (PAH) in any of the following subtypes, in accordance with European Society of Cardiology European Respiratory Society (ESC/ERS) Guidelines:
• Idiopathic PAH
• Heritable PAH
• Drug/toxin-induced PAH
• Connective tissue disease (CTD)-associated PAH
• PAH associated with congenital heart disease-related to simple systemic-to-pulmonary shunt at least 1 year following repair.
• PAH diagnosis for at least 3 months prior to Screening.
• New York Heart Association (NYHA) or World Health Organization (WHO) functional class II-IV.
• Participants must be on stable PAH therapy consisting of 1 to 3 medications from the following classes:
• Endothelin receptor antagonists (eg, ambrisentan, bosentan, macitentan) for at least 90 days prior to Screening with the last 30 days on stable dose
• Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil) for at least 90 days prior to Screening with the last 30 days on stable dose
• Guanylate cyclase stimulator (eg, riociguat) for at least 90 days prior to Screening with the last 30 days on stable dose
• Activin signaling inhibitor (e.g., sotatercept) for at least 6 months prior to Screening, with the last 3 months on stable dose and meeting all the following conditions:
• no active clinically significant bleeding (eg, epistaxis and gingival bleeding requiring medical interventions) within the past 3 months.
• no history of major bleeding events or risks (eg, gastrointestinal or intracranial bleeding) within the past 6 months.

You may not qualify if:

• Clinically significant left heart disease, including left-sided valvular disease, left ventricular systolic or diastolic dysfunction, echocardiographic findings suggestive of post-capillary pulmonary hypertension, unstable ischemic heart disease, or unstable arrhythmias.
• Evidence of airflow obstruction defined by forced expiratory volume in 1 second (FEV1) per forced vital capacity (FVC) \<0.7.
• Evidence of significant restrictive lung disease as evidenced by FVC \<70% predicted normal.
• Evidence of chronic thromboembolic disease or recent (within 6 months of Screening) acute pulmonary embolism.
• Known hypersensitivity or contraindication to treprostinil or TPIP or TPIP formulation excipients (e.g., mannitol, leucine).
• Any other medical or psychological condition including relevant laboratory abnormalities at Screening that, in the opinion of the Investigator, suggest a new and/or insufficiently understood disease and/or may present an unreasonable risk to the study participant as a result of his/her participation in this clinical trial, may impede their ability complete the study or the study assessments or confound the outcomes of the trial.

Sponsors & Collaborators

• Insmed Incorporated: lead

Study Sites (26)

USA012

Los Angeles, California, 90027, United States

RECRUITING

USA008

Santa Barbara, California, 93105, United States

RECRUITING

USA005

Torrance, California, 90502, United States

RECRUITING

USA010

Kansas City, Kansas, 66160, United States

RECRUITING

USA028

Omaha, Nebraska, 68198-6450, United States

RECRUITING

USA013

Rochester, New York, 14642, United States

RECRUITING

USA006

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

USA007

Anderson, South Carolina, 29621, United States

RECRUITING

ARG001

Buenos Aires, Buenos Aires F.D., C1425AIN, Argentina

RECRUITING

ARG004

Río Cuarto, Córdoba Province, X5080AEV, Argentina

RECRUITING

AUS002

Camperdown, New South Wales, 2050, Australia

RECRUITING

AUS003

Westmead, New South Wales, 2145, Australia

RECRUITING

ISR001

Jerusalem, 9112001, Israel

RECRUITING

ISR004

Petah Tikva, 4941492, Israel

RECRUITING

ISR005

Ramat Gan, 5265601, Israel

RECRUITING

ISR003

Tel Aviv, 6423906, Israel

RECRUITING

JPN011

Narashino, Chiba, 275-8580, Japan

RECRUITING

JPN015

Yahatanishi-ku, Kita Kyushu-shi, Fukuoka, 807-8556, Japan

RECRUITING

JPN007

Sapporo, Hokkaido, 060-8543, Japan

RECRUITING

JPN002

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

JPN014

Kobe, Hyōgo, 650-0017, Japan

RECRUITING

JPN003

Okayama, Okayama-ken, 701-1192, Japan

RECRUITING

JPN017

Minato-ku, Tokyo, 108-8329, Japan

RECRUITING

NZL001

Auckland, 2025, New Zealand

RECRUITING

NZL003

Dunedin, 9016, New Zealand

RECRUITING

NZL002

Hamilton, 3240, New Zealand

RECRUITING

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Insmed Medical Information

CONTACT

18444467633; medicalinformation@insmed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2026
• First Posted: March 19, 2026
• Study Start: July 21, 2026
• Primary Completion (Estimated): December 28, 2028
• Study Completion (Estimated): January 28, 2029
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3); AR (2); IL (4); AU (2); US (8); JP (7)