Open-label Extension of Oral Treprostinil in Subjects With PH Associated With HFpEF

An Open-label Extension Study of Oral Treprostinil in Subjects With Pulmonary Hypertension (PH) Associated With Heart Failure With Preserved Ejection Fraction (HFpEF) - A Long-term Follow-up to Study TDE-HF-301

This was an open-label study to evaluate the safety of continued therapy with oral treprostinil in subjects who completed Study TDE-HF-301. This study provided long-term, open-label data regarding the effect of continued long-term oral treprostinil therapy for the treatment of pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF). Subject visits occurred at Baseline, Weeks 6, 12, 18, 24, and every 12 weeks thereafter until either oral treprostinil was commercially available to treat PH associated with HFpEF or the study was discontinued by the Sponsor.

The Sponsor terminated Studies TDE-HF-301 and TDE-HF-302 on 14 October 2019 due to slow enrollment. Safety data from the final subject in Study TDE-HF-302 were recorded on 02 March 2020. Due to the lower than expected number of subjects enrolled, the planned secondary efficacy-related endpoints were not analyzed.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Hypertension Associated With HFpEF
• Intervention / Treatment: Drug: Oral treprostinil

Detailed Description

Study TDE-HF-302 was a multicenter, open-label study in subjects participating and completing all required visits for Study TDE-HF-301. This study assessed the long-term safety of oral treprostinil in subjects with PH associated with HFpEF.

Subjects received oral treprostinil as 0.125-, 0.25-, 1-, and 2.5-mg sustained-release tablets. For subjects who were randomly allocated to receive oral treprostinil in Study TDE-HF-301, the initial dose of oral treprostinil was the same as the final dose in Study TDE-HF-301. Subjects randomly allocated to receive placebo in Study TDE-HF-301 were administered the initial dose of oral treprostinil at 0.125 mg 3 times daily (TID). Dose increases could occur in 0.125-mg increments every 72 hours at the discretion of the Investigator up to 6 mg TID, the maximum allowable dose determined by the Data Monitoring Committee during Study TDE-HF-301. Doses of study drug were to be increased in the absence of dose-limiting drug-related adverse events (AEs) to ensure that each subject received the optimal dose throughout the study. Subjects returned for visits at Weeks 6, 12, 18, and 24, and every 12 weeks thereafter. Subjects who terminated the study early were asked to return to the study center for a final evaluation.

Safety assessments consisted of AEs, clinical laboratory parameters, and clinical assessment of heart failure signs and symptoms.

Due to the lower than expected number of subjects enrolled, the planned secondary efficacy-related endpoints were not analyzed.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center Phoenix
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Los Angeles, California, United States, 90211
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90073
      • VA Healthcare System of Greater Los Angeles
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles Pulmonary Division
    • Sacramento, California, United States, 95817
      • University of California - Davis Medical Center
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Aurora, Colorado, United States, 80012
      • Aurora Denver Cardiology Associates
    • Denver, Colorado, United States, 80206
      • National Jewish Health
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
    • Washington, District of Columbia, United States, 20037
      • Medical Faculty Associates, George Washington University
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Cardiology Associates
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Jacksonville, Florida, United States, 33204
      • St. Vincent's Lung, Sleep, and Critical Care Specialists
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, P.A.
    • Orlando, Florida, United States, 32806
      • Florida Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida ; Tampa General Hospital
    • Weston, Florida, United States, 33331
      • Cleveland Clinic of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Augusta, Georgia, United States, 30912
      • Augusta University
    • Austell, Georgia, United States, 30309
      • Piedmont Physicians Georgia Lung
    • Marietta, Georgia, United States, 30060
      • Wellstar Medical Group
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
    • Peoria, Illinois, United States, 61614
      • OSF Healthcare
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Saint Vincent Hospital and Health Services
    • Indianapolis, Indiana, United States, 46250
      • Community Heart and Vascular Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Methodist Research Institute, INC
  • Iowa
    • Iowa City, Iowa, United States, 55242
      • University of Iowa Hospitals and Clinics
    • West Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Physicians Outpatient Center
  • Maine
    • South Portland, Maine, United States, 04106
      • Chest Medicine Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Brighton, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Medical Group
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Luke's Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Barnabas Health Lung Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Syracuse, New York, United States, 13066
      • Pulmonary Health Physicians, PC
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Cardiology Associates
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Pinehurst, North Carolina, United States, 28374
      • Pinehurst Medical Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center The Christ Hospital Health Network
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
    • Toledo, Ohio, United States, 43614
      • University of Toldedo Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • The Oregon Clinic
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17601
      • Lancaster General Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Vitalink Research - Anderson
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Pulmonary and Sleep Medicine
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation
    • Knoxville, Tennessee, United States, 37909
      • Summit Medical Group
    • Nashville, Tennessee, United States, 37232-2650
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
    • Lubbock, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
  • Utah
    • Murray, Utah, United States, 84143
      • Intermountain Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Heart and Vascular Institute
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Roanoke, Virginia, United States, 24014
      • Carilion Clinic
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject participated in Study TDE-HF-301, remained on study drug, was compliant with study procedures and assessments during Study TDE-HF-301, and completed through Week 24 of that study.

Exclusion Criteria:

1. The subject was pregnant or lactating.
2. The subject was prematurely discontinued from Study TDE-HF-301 for any reason.
3. The subject developed a concurrent illness or condition during Study TDE-HF-301, which, in the opinion of the Investigator, represented a risk to the subject's overall health if they enrolled in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral treprostinil; Sustained-release tablets for TID administration	Drug: Oral treprostinil; Sustained-release oral tablets for TID administration; Other Names: Treprostinil diethanolamine, Treprostinil diolamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Safety of Oral Treprostinil in Subjects With PH Associated With HFpEF for Subjects Who Completed Study TDE-HF-301	The primary objective of this study was to evaluate the long-term safety of oral treprostinil in subjects with PH associated with HFpEF for subjects who completed Study TDE-HF-301. The number of subjects with adverse events during the study is reported as the primary outcome measure, which was the only outcome measurement reported for this Sponsor-terminated study.	Baseline through study completion, up to approximately 25 months

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2018
• Primary Completion (Actual): March 2, 2020
• Study Completion (Actual): March 2, 2020

Study Registration Dates

• First Submitted: January 31, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: September 25, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; HFpEF; Oral Treprostinil; 6-Minute Walk Test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-HF-302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No