A Study of Treprostinil Palmitil Inhalation Powder (TPIP) In Pulmonary Arterial Hypertension (PAH)

An Open-Label Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Arterial Hypertension

The main purpose of this study is to evaluate the safety and tolerability of single dose of treprostinil palmitil inhalation powder (TPIP) in participants with pulmonary arterial hypertension (PAH).

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Treprostinil Palmitil

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021-9800
      • USA002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be ≥ 18 years of age at the time of signing the informed consent

• Participants must have a diagnosis of World Health Organization Group 1 Pulmonary Hypertension (PH) (PAH) with the following characteristics

  1. Etiology of idiopathic, heritable, drug/toxin-induced or connective tissue disease (CTD)-related PAH
  2. Right heart catheterization with the following hemodynamic findings:
• Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest,
• Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg, and
• Pulmonary vascular resistance (PVR) of ≥ 3 Wood Units (WU)
• No change in pulmonary hypertension medications (eg, ambrisentan, bosentan, macitentan, sildenafil, tadalafil, riociguat) or dosage for at least 90 days prior to Screening
• No change in diuretic use or dosage for at least 30 days prior to Screening
• Body mass index (BMI) within the range 18.0 - 32.0 kg/m^2 (inclusive)
• Male participants: Male participants and their female partners of childbearing potential must agree to use highly effective contraception from Study Day 1 to at least 90 days after dosing
• Female participants: Women of child-bearing potential (WOCPB, defined as premenopausal, not surgically sterile for at least 3 months prior to Screening) must use a highly effective contraception method and agree to be tested for pregnancy from at Screening, Baseline, and 30 days after dosing
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

Exclusion Criteria:

• Any PH other than idiopathic, hereditary, drug/toxin-induced, or connective tissue disease (CTD) associated PAH (eg, congenital heart disease-associated PAH, portal hypertension-associated PAH, PH belonging to Groups 2 through 5)
• Allergy, or documented hypersensitivity or contraindication, to the ingredients of treprostinil palmitil inhalation powder (TPIP) or treprostinil (TRE)
• Previous intolerance to prostacyclin analogs or receptor agonists (eg, selexipag) per investigator discretion
• History of anaphylaxis or previously documented hypersensitivity reaction to any drug per Investigator discretion
• History of heart disease including left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant valvular, constrictive, or atherosclerotic heart disease (myocardial infarction, etc)

• Active liver disease or hepatic dysfunction manifested as:

  1. Elevated liver function test results (ALT or AST > 2 × ULN) at Screening
  2. Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN; ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) at Screening.
  3. Known hepatic or biliary abnormalities, not including Gilbert's syndrome or asymptomatic gallstones at Screening.
• History of HIV infection/positive HIV serology test result at Screening
• History of active/chronic Hepatitis B or C/ positive hepatitis B or C serology test result at Screening
• History of abnormal bleeding or bruising
• 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
• Active and current symptomatic infection by SARS CoV 2
• Participants with current or recent (past 4 weeks) 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
• Participants receiving triple combination therapy for PAH consisting of endothelin receptor agonists, phosphoesterase type 5 inhibitors, and guanylate cyclase stimulators (riociguat)
• Participants receiving prostanoids/prostacyclin agonists
• Participants receiving potent CYP2C8 inhibitors, such as gemfibrozil
• Have participated in any other interventional clinical studies within 30 days of Baseline
• Current or history of substance and/or alcohol abuse
• Current user of cigarettes or e-cigarettes
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treprostinil Palmitil Inhalation Powder; Participant received a single dose of TPIP 112.5 micrograms (μg) via oral inhalation on Day 1. The participant then entered into a 16-week Extended Use Treatment (EUT) Period during which TPIP, administered via oral inhalation, was titrated up to a mean daily dose of 320 μg.	Drug: Treprostinil Palmitil; Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler; Other Names: INS1009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Experience a Treatment Emergent Adverse Event (TEAE)	Up to 150 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Pulmonary Vascular Resistance (PVR) After TPIP Administration	Day 1: Pre-treatment (Baseline), 8 and 24 hours post-treatment
Maximum Observed Concentration (Cmax) of Treprostinil (TRE) in Plasma	Pre-dose and multiple timepoints post-dose up to Day 2
Time to Maximum Concentration (Tmax) of Treprostinil (TRE) in Plasma	Pre-dose and multiple timepoints post-dose up to Day 2
Area Under the Concentration-time Curve From Time 0 to Time of the Last Measurable Concentration (AUClast) of Treprostinil (TRE) in Plasma	Pre-dose and multiple timepoints post-dose up to Day 2
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of Treprostinil (TRE) in Pasma	Pre-dose and multiple timepoints post-dose up to Day 2
Elimination Half-life (t1/2) of Treprostinil (TRE) in Plasma	Pre-dose and multiple timepoints post-dose up to Day 2

Collaborators and Investigators

• Sponsor: Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): August 26, 2022

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Arterial Hypertension; Treprostinil Palmitil; Treprostinil Palmitil Inhalation Powder
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Hypertension, Pulmonary; Hypertension; Respiratory Aspiration; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: INS1009-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No