Oral Treprostinil in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Fibrosis; Pulmonary Hypertension
• Intervention / Treatment: Drug: Oral treprostinil

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center Phoenix Advanced Lung Disease
  • California
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles - Pulmonary Division
    • Sacramento, California, United States, 95817
      • University of California - Davis Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Maryland
    • Baltiomore, Maryland, United States, 21205
      • Johns Hopkins University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • CLC Pulmonary Hypertension Clinic Division of Pulmonary, Allergy and Critical Care Medicine UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: United Therapeutics
• Investigators: Principal Investigator: Rajan Saggar, MD, University of California, Los Angeles - Pulmonary Division

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Estimate): February 9, 2016
• Last Update Submitted That Met QC Criteria: February 5, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Hypertension; Pulmonary Fibrosis; Hypertension, Pulmonary; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study is withdrawn. There is no data to share.