A Study to Evaluate the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and tolerability of treprostinil palmitil inhalation powder (TPIP) compared with placebo

Official Title
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A Phase 2, Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Evaluate the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Treprostinil Palmitil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females must be ≥ 18 to ≤ 80 years of age at the time of signing the informed consent form (ICF). Diagnosis of pulmonary hypertension (PH) associated with interstitial lung disease (ILD) (including idiopathic interstitial pneumonia [IIP], idiopathic pulmonary fibrosis [IPF], connective tissue disease [CTD], sarcoidosis). Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: Male participants who are not sterile, with 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. Male participants with women of child bearing potential (WOCBP) partner must use a condom in order to avoid potential exposure to embryo/fetus. - Female participants: Women must be postmenopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile, (ie,hysterectomy and/or bilateral salpingo-oophorectomy) 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. - Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Exclusion Criteria: Primary diagnosis of chronic obstructive pulmonary disease (COPD). Allergy, or documented hypersensitivity or contraindication to TPIP or treprostinil (TRE) or mannitol (an excipient of the TPIP formulation). Received or currently treated with riociguat, endothelin receptor antagonists, selexipag, phosphodiesterase 5 (PDE5) inhibitors and/or prostacyclin analogues within 30 days prior to Screening. Started therapy with pirfenidone or nintedanib < 90 days prior to Screening, OR, if already receiving either medication, there is a dose change within 30 days of Screening Visit. Any known ventricular or supraventricular tachyarrhythmia (except for paroxysmal atrial fibrillation), and/or 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 cardiopulmonary rehabilitation program within 30 days of the first Screening Visit. Participation in the maintenance program of a cardiopulmonary rehabilitation program is allowed. Acutely decompensated heart failure within 30 days of Screening Visit. Active and current symptomatic coronavirus disease 2019 (COVID-19) and/or previous diagnosis of moderate to severe disease, or hospitalization due to COVID-19. Supplemental oxygen requirement > 10L/min at rest at Screening. Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of the first dose of study drug (may be rescreened at appropriate time). Current or recent (past 30 days) lower respiratory tract infection (may be rescreened at appropriate time). Any form of congenital heart disease or congenital heart defect (repaired or unrepaired) other than a patent foramen ovale. History of alcohol or drug abuse within 6 months prior to Screening. Current use of cigarettes (as defined by Center for Disease Control (CDC)) or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime and who currently smokes either every day or some days. Participants who currently inhale marijuana (recreational or medical). Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6-minute walk test (6MWT) (eg, angina pectoris, claudication, musculoskeletal disorder, need for walking aids).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treprostinil Palmitil<br>Participants will be administered TPIP once per day at a starting dose of 80 micrograms (μg). Participants will be titrated up 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. | Drug: Treprostinil Palmitil<br>* Oral inhalation using a capsule-based dry powder inhaler device.<br>* Other names: INS1009;|
| Placebo Comparator: Placebo<br>Participants will be administered a placebo matching TPIP once daily. | Drug: Placebo<br>* Oral inhalation using a capsule-based dry powder inhaler device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience Any Number of Treatment Emergent Adverse Events (TEAEs) |  | Up to Day 140 | 
| Number of Participants Who Experience Any Number of Serious Adverse Events (SAEs) |  | Up to Day 140 | 
| Change from Baseline in Saturation of Peripheral Capillary Oxygenation (SpO2) Levels |  | Pre-, during, and post- 6-minute walk test (6MWT) at Baseline, Week 5, Week 10, and Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| Cmax of Treprostinil |  | Day 1 to Week 16 | 
| Time to Maximum Plasma Concentration (Tmax) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| Tmax of Treprostinil |  | Day 1 to Week 16 | 
| Area Under Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUCtau) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| AUCtau of Treprostinil |  | Day 1 to Week 16 | 
| Area Under Concentration-time Curve From 0 to Infinity (AUC∞) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| AUC∞ of Treprostinil |  | Day 1 to Week 16 | 
| Area Under Concentration-time Curve From Time 0 to Last Measurable Concentration (AUClast) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| AUClast of Treprostinil |  | Day 1 to Week 16 | 
| Apparent Total Clearance (CL/F) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| CL/F of Treprostinil |  | Day 1 to Week 16 | 
| Elimination Half-life (t1/2) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| t1/2 of Treprostinil |  | Day 1 to Week 16 | 
| Apparent Volume of Distribution After Terminal Phase (Vd/F) of Treprostinil Palmitil |  | Day 1 to Week 16 | 
| Vd/F of Treprostinil |  | Day 1 to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Hypertension, Interstitial Lung Disease, Treprostinil Palmitil