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

Phase 2

Terminated

Conditions: Pulmonary Arterial Hypertension

Interventions: Drug: Treprostinil Palmitil

Registration Number: NCT04791514

Lead Sponsor: Insmed Incorporated

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treprostinil Palmitil Inhalation Powder	Treprostinil Palmitil	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experience a Treatment Emergent Adverse Event (TEAE)	Up to 150 days

Secondary Outcome Measures

Name	Time	Method
Time to Maximum Concentration (Tmax) of Treprostinil (TRE) in Plasma	Pre-dose and multiple timepoints post-dose up to Day 2
Maximum Observed Concentration (Cmax) of Treprostinil (TRE) in Plasma	Pre-dose and multiple timepoints post-dose up to Day 2
Change From Baseline in Pulmonary Vascular Resistance (PVR) After TPIP Administration	Day 1: Pre-treatment (Baseline), 8 and 24 hours post-treatment
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
Elimination Half-life (t1/2) 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