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

Study Overview
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Brief Summary
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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).

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

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Treprostinil Palmitil


Participation Criteria
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Eligibility Criteria
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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 Etiology of idiopathic, heritable, drug/toxin-induced or connective tissue disease (CTD)-related PAH 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: Elevated liver function test results (ALT or AST > 2 × ULN) at Screening Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN; ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) at Screening. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treprostinil Palmitil Inhalation Powder<br>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<br>* Administered by oral inhalation using a Plastiape capsule-based dry powder inhaler<br>* Other names: INS1009;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Arterial Hypertension, Treprostinil Palmitil Inhalation Powder, Treprostinil Palmitil