Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis

Study Overview
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Brief Summary
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This multicenter, randomized, open-label study will assess the safety and efficacy of oral treprostinil in subjects diagnosed with pulmonary hypertension associated with pulmonary fibrosis.

Detailed Description
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This study will evaluate how oral treprostinil can affect pulmonary vascular resistance, as assessed by right heart catheterization, and exercise capacity, as assessed by the Six-Minute Walk Test. This is a 16-week study that will involve at least 10 clinical trial centers. The expected enrollment period is around 24 months and 52 subjects will be entered into the study.

Official Title
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Multicenter, Randomized, Open Label Trial to Evaluate the Safety and Efficacy of Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis

Conditions
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Pulmonary Hypertension, Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Oral treprostinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily gives informed consent Must meet criteria for lung transplant referral but is not required to be on an active lung transplant list Stable and significant diffuse parenchymal lung disease with a diagnosis of interstitial lung disease 6MWD greater than or equal to 75 meters Right heart catheterization with a mean pulmonary arterial pressure >= 30 mgHg, pulmonary capillary wedge pressure <= 15 mmHg and pulmonary vascular resistance > 240 dynes Echo-Doppler examination showing evidence of right ventricular dysfunction and normal left diastolic ventricular function Either not receiving any PAH-approved oral therapy, or is receiving monotherapy (ERA, PDE-5I, or riociguat) for > 60 days and receiving a stable dose for > 30 days prior to enrollment Able to communicate effectively with study personnel and will to be cooperative with protocol requirements Exclusion Criteria: History of repaired or unrepaired congenital heart disease Received prostanoid therapy in the past 30 days, or has shown an intolerance or lack of efficacy to prostanoid therapy resulting in discontinuation or inability to titrate prostacyclins Diagnosis of sarcoidosis History of thromboembolic disease Chronic renal insufficiency Pregnancy or lactating Currently receiving an investigational drug, has an investigational device in place, or has participated in an investigational drug or device study within 30 days prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individual Maximum Tolerated Dose (iMTD)<br>Subjects are allowed to titrate oral treprostinil up to a maximum dose of 12 mg TID. | Drug: Oral treprostinil<br>* Oral treprostinil will be administered as TID dosing for up to 16 Weeks.<br>* Other names: Orenitram;|
| Experimental: Fixed Dose (FD)<br>Subjects are allowed to titrate oral treprostinil up to a maximum dose of 1 mg TID. | Drug: Oral treprostinil<br>* Oral treprostinil will be administered as TID dosing for up to 16 Weeks.<br>* Other names: Orenitram;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulmonary vascular resistance (PVR) | Change in PVR between iMTD and fixed dose groups | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Six-minute walk distance (6MWD) | Change in 6MWD between iMTD and fixed dose groups | Baseline to Week 16 | 
| Change in N-terminal pro-brain natriuretic peptide (NT-ProBNP) | Change in NT-ProBNP between iMTD and fixed dose groups | Baseline to Week 16 |