An Open-Label Extension Trial of UT-15C Sustained-release (SR) in Subjects With Pulmonary Arterial Hypertension (FREEDOM-EXT)

April 14, 2021 updated by: United Therapeutics

An Open-Label Extension Trial of UT-15C SR in Subjects With Pulmonary Arterial Hypertension

This study provided/continued to provide oral treprostinil (UT-15C SR; treprostinil diethanolamine) to eligible subjects who participated in Studies TDE-PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, and TDE-PH-308. The study assessed the long term safety of oral treprostinil and the effect of continued treatment with oral treprostinil on exercise capacity after 1 year of treatment.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This was an international, multicenter, open-label study designed to provide oral treprostinil for eligible subjects who participated in Studies TDE-PH-301, TDE-PH-302, TDE-PH-308, TDE-PH-202, TDE PH 203, and TDE-PH-205. Subjects randomly allocated to receive oral treprostinil in Studies TDE-PH-301, TDE-PH-302, or TDE-PH-308 and enrolled in this open-label study completed visits at Months 6, 12, 24, 36, and yearly visits thereafter. Subjects randomly allocated to receive placebo in Studies TDE-PH-301, TDE-PH-302, or TDE-PH-308 completed visits at Months 3, 6, 12, 24, 36, and yearly visits thereafter. Subjects that transitioned from Studies TDE-PH-202, TDE-PH-203, and TDE-PH-205 (that had an open-label study design) followed the regimen for subjects receiving oral treprostinil. A 6-Minute Walk Test (6MWT) and Borg dyspnea score were conducted at the visit which occurred 12 months after the subject's first exposure to oral treprostinil.

Adverse events (AEs) were reported continuously throughout the study; any AEs ongoing at the time of discharge from Studies TDE PH-301, TDE PH-302, TDE-PH-308, TDE-PH-202, TDE-PH-203, and TDE-PH-205 were recorded as AEs and marked as "ongoing from previous study" in the subject's electronic Case Report Form (eCRF). Study drug dosing and pulmonary arterial hypertension (PAH) concomitant medication usage were assessed at each scheduled study visit and recorded in the subject's eCRF.

Study Type

Interventional

Enrollment (Actual)

894

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Chermside West, Australia, 4032
        • The Prince Charles Hospital
      • Darlinghurst, Australia, 2010
        • Heart/Lung Transplant Unit - St. Vincent's Hospital
      • Melbourne, Australia, 3004
        • The Alfred Hospital
      • Perth, Australia
        • Royal Perth Hospital
      • Wein, Austria
        • Medical University Graz
      • Wien, Austria
        • Medizininische Universitaet Wien
      • Wien, Austria
        • Universitaetsklinik für Innere Medizin Innsbruck
      • Brussels, Belgium
        • Department of Cardiology Erasme University Hospital
      • Leuven, Belgium
        • University Hospital Gasthuisberg
    • Alberta
      • Calgary, Alberta, Canada, T1Y 6J4
        • Peter Lougheed Centre
      • Edmonton, Alberta, Canada, T6G 2B7
        • University of Alberta Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Vancouver Coastal Health Authority Vancouver General Hospital
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • Toronto General Hospital
      • Toronto, Ontario, Canada, N6A 4G5
        • London Health Sciences Center Victoria Hospital
    • Quebec
      • Montréal, Quebec, Canada, H3T 1E2
        • Sir Mortimer B. Davis Jewish General Hospital
      • Beijing, China
        • Beijing Shijitan Hospital, Cadres Respiratory Department
      • Beijing, China
        • Peking Union Medical College Hospital, Respiratory Medicine Department
      • Shanghai, China
        • Shanghai Pulmonary Hospital, Respiratory Medicine Department
      • Bernin, France
        • PMAC, Clinique de Pneumologie
      • Brest, France
        • Centre d'Investigation Clinique Hôpital La Cavale Blanche - CHU Brest
      • Clamart, France
        • Hospital Antoine Beclere
      • Lille Cedex, France
        • Hospital Claude Huriez
      • Lyon, France
        • Hopital Louis Pradel
      • Montpellier cedex 5, France, 34295
        • CHU Arnaud de Villeneuve - Service maladies respiratoires
      • Toulouse, France
        • Service de Pneumologie Centre de Competence pour l'HTAP- Pole des Voies Respiratoires Hôpital Larrey
    • Pessac Cedex
      • Pessac, Pessac Cedex, France, 33604
        • Service Chirurgie Thoracique, Hôpital Haut Levêque
      • Dresden, Germany, 01307
        • Universitätsklinikum Dresden Abtl. Pneumologie
      • Greifswald, Germany, 17475
        • University Hospital Greifswald
      • Hamburg, Germany
        • DRK Kliniken Berlin Köpenick
      • Hamburg, Germany
        • Universitätsklinikum Hamburg Eppendorf
      • Hamburg, Germany
        • Universitätsklinkium Köln Klinik III für Innere Medizin
      • Hamburg, Germany
        • Zentrum für Lungenhochdruck Thoraxklinik am Universitätsklinikum Heidelberg
      • Hannover, Germany
        • Medizinische Hochschule Hannover (MHH)
      • Heidelberg, Germany, 69120
        • Dept. of Internal Medicine III University Heidelberg
      • Ahmedabad, India, 380054
        • Life Care Institute of Medical Sciences & Research
      • Chennai, India
        • Sri Ramachandra MedicaL College & Research Institute
      • Coimbatore, India
        • G. Kuppuswamy Naidu Memorial Hospital
      • Hyderabad, India, 500038
        • PRIME Hospitals
      • New Delhi, India, 110060
        • Sir Ganga Ram Hospital
      • Pune, India
        • Ruby Hall Clinic
      • Visakhapatnam, India
        • Queen's NRI Hospital
    • Gujarat
      • Ahmedabad, Gujarat, India, 380054
        • Care Institute of Medical Sciences
    • Karnataka
      • Bangalore, Karnataka, India, 560034
        • Narayana Hrudayalaya Hospitals
    • Maharashtra
      • Mumbai, Maharashtra, India, 400012
        • Asian Heart Institute & Research Centre Pvt. Ltd.
      • Pune, Maharashtra, India, 411030
        • Poona hospital and research centre
      • Dublin, Ireland
        • Pulmonary Hypertension Unit Centre for Lung Health Mater Misericordiae University Hospital
      • Haifa, Israel, 31096
        • Rambam Medical Center
      • Haifa, Israel
        • The Lady Davis Carmel Medical Center
      • Jerusalem, Israel
        • Hadassah Hebrew University Medical Center
      • Petah Tiqva, Israel
        • Pulmonary Institute Rabin Medical Center (Belinson Kampus)
      • Ramat Gan, Israel
        • Pulmonary Institute Chaim Sheba Medical Center
      • Bologna, Italy
        • Policlinico S. Orsola Malpighi - Università degli studi di Bologna
      • Naples, Italy
        • Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.
      • Napoli, Italy
        • Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.
      • Rome, Italy
        • Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
      • Mexico City, Mexico, 14080
        • Instituto Nacional de Cardiologia
      • Monterrey, Mexico, 64460
        • Hospital Universitario de la UANL
      • Monterrey, Mexico, 64718
        • Unidad de Investigacion Clinica en Medicina S.C.
      • Amsterdam, Netherlands
        • Radboud University Nijmegen Medical Center
      • Amsterdam, Netherlands
        • VU Medish Centrum
      • Kraków, Poland, 31-202
        • Klinika Chorób Serca i Naczyń, Krakowski Szpital Specjalistyczny im. Jana Pawla II
      • Warsaw, Poland
        • Europejskie Centrum Zdrowia Otwock
      • Wroclaw, Poland, 51-124
        • Oddzial Kardiologiczny
      • Lisbon, Portugal
        • Servico de Cardiologia Hospital de Santa Marta
      • Guaynabo, Puerto Rico, 00968
        • Auxilio Mutuo Hospital CardioPulmonary Research Center
      • Barcelona, Spain
        • Hospital Clinic I Provincial
      • Barcelona, Spain
        • Hospital Vall d'Hebron
      • Madrid, Spain
        • Hospital 12 de Octubre
      • Lund, Sweden, SE 22185
        • Skåne University Hospital
      • Cambridge, United Kingdom
        • Papworth Hospital
      • Glasgow, United Kingdom
        • Papworth Hospital NHS Foundation Trust
      • London, United Kingdom
        • Royal Free Hospital
      • Newcastle, United Kingdom
        • Freeman Hospital
      • Sheffield, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • The Kirklin Clinic
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Phoenix
      • Phoenix, Arizona, United States, 85013
        • Arizona Pulmonary Specialists, Ltd.
      • Phoenix, Arizona, United States
        • St. Joseph's Hospital and Medical Center
      • Tucson, Arizona, United States, 85724
        • University Medical Center
      • Tucson, Arizona, United States, 85724
        • University of Arizona Clinical and Translational Science (CATS) Research Center
    • California
      • Fresno, California, United States, 93701
        • University of California, San Francisco-Fresno
      • Los Angeles, California, United States, 90095
        • David Geffen School of Medicine at UCLA
      • Los Angeles, California, United States, 90073
        • West Los Angeles VA Healthcare Center
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
      • San Diego, California, United States, 30322
        • UCSD Medical Center
      • San Francisco, California, United States, 94118
        • University of California San Francisco Medical Center
      • Stanford, California, United States, 94305-5351
        • Stanford University, Pulmonary and Critical Care Medicine
      • Torrance, California, United States, 90502
        • Harbor-UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • The Children's Hospital
      • Aurora, Colorado, United States, 80045
        • University of Colorado Health Science Center
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida College of Medicine Jacksonville
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • The Emory Clinic
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Hospitals
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Kentuckiana Pulmonary Associates
    • Louisiana
      • Alexandria, Louisiana, United States, 71301
        • Alexandria Cardiology Clinic
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Outpatient Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02114
        • Brigham And Woman's Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48103
        • University of Michigan Health System
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center, Fairview
      • Rochester, Minnesota, United States, 55902
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110-1093
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68198-5300
        • University of Nebraska Medical Center
    • New Jersey
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
    • New York
      • Mineola, New York, United States, 11501
        • Winthrop University Hospital
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Rochester, New York, United States, 14643
        • Mary Parkes Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina Hospitals
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • The Carl and Ethyl Linder Center for Research and Education at the Christ Church
      • Cincinnati, Ohio, United States, 45267-0564
        • University of Cincinnati
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
      • Columbus, Ohio, United States, 43210
        • Ohio State University
      • Toledo, Ohio, United States, 43614
        • The University of Toledo Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Sciences University
      • Portland, Oregon, United States, 97210
        • Legacy Pulmonary Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Presbyterian Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2650
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77030
        • University of Texas Medical School
      • San Antonio, Texas, United States, 78229
        • The University of Texas Health Science Center at San Antonio
    • Utah
      • Murray, Utah, United States, 84157-7000
        • Intermountain Medical Center
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Fairfax Hospital
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Cardiovascular Services

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The subject remained on study drug and completed all assessments during the Treatment Phase of the previous study (TDE-PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE PH-302, or TDE-PH-308) OR the subject permanently discontinued study drug during the Treatment Phase of the previous study due to clinical worsening (as defined in the protocol of the previous study), completed premature termination assessments prior to discontinuing study drug, completed all remaining scheduled study visits, AND received placebo during the Treatment Phase of the previous studies OR the subject was randomized into Group 1 or Group 2 in Study TDE PH 202, permanently discontinued study drug during the 12-week Treatment Phase due to clinical worsening, completed all premature termination assessments prior to discontinuing study drug, and completed all remaining scheduled study visits and assessments (with the exception of the hemodynamic measurements) through Week 12. Such subjects should have started treatment with oral treprostinil in the open-label study at 0.25 mg twice daily (BID).
  2. The subject voluntarily gave informed consent to participate in the study.
  3. Women of childbearing potential includes any female who had experienced menarche and who had not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or was not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Sexually active women of childbearing potential must have used 2 effective forms of contraception during the length of the study. Medically acceptable forms of effective contraception included: (1) approved hormonal contraceptives (such as birth control pills), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, (3) an intrauterine device, (4) partner vasectomy, or (5) abstinence. Males participating in the study must have used a condom during the length of the study, and for at least 48 hours after discontinuing study medication. Protocol Amendment A.1AU included the required assessment for Austrian subjects to perform urine pregnancy tests every 4 weeks during the study.

Exclusion Criteria:

  1. The subject permanently discontinued study drug during the previous study (TDE PH 202, TDE-PH-203, TDE PH 205, TDE-PH-301, TDE-PH-302, or TDE PH 308) due to treatment-related adverse events (AEs).
  2. The subject permanently discontinued study drug during the Treatment Phase of the previous study (TDE-PH-202, TDE-PH-203, TDE-PH-205, TDE-PH-301, TDE-PH-302, or TDE-PH-308) due to clinical worsening (as defined in those study protocols) and did not undergo premature termination assessments prior to discontinuing study drug, and/or did not complete all remaining study visits through the final scheduled visit.
  3. The subject prematurely discontinued study drug during the Treatment Phase of the previous study due to clinical worsening (as defined in those study protocols), completed premature termination assessments prior to discontinuing study drug, completed all remaining scheduled study visits AND received oral treprostinil during the Treatment Phase of the previous study (TDE PH-202, TDE-PH-203, TDE-PH-301, TDE-PH-302, or TDE PH-308). Subjects enrolled in Study TDE-PH-202 who were randomized into the individual maximum tolerated dose (iMTD) group who clinically worsened could not participate. Subjects who permanently discontinued study drug during the 12-week Treatment Phase due to treatment-related AEs were not eligible even if they completed all remaining scheduled study visits. Subjects who permanently discontinued study drug during the 12 week Treatment Phase and did not undergo premature termination assessments prior to discontinuing study drug and/or who did not complete all remaining study visits through the Week 12 visit were also not eligible.
  4. The subject developed any concurrent illness or condition during the conduct of the previous study, including but not restricted to: sleep apnea, chronic renal insufficiency, anemia, uncontrolled systemic hypertension, or left sided heart disease, unless their physician felt that entry into this study would not be detrimental to their overall health.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Treprostinil
Subjects from previous studies TDE-PH-202 (NCT01104870), TDE-PH-203 (NCT01477333), and TDE-PH-205 (NCT01588405), TDE-PH-301 (NCT00325442), TDE-PH-302 (NCT00325403), or TDE PH-308 (NCT00887978). Subjects were instructed to take the appropriate amount of 0.125, 0.25, 0.5, 1, and/or 2.5 mg tablets based upon their prescribed dose. Investigators were instructed to increase the dose of oral treprostinil in the absence of dose limiting drug-related AEs to ensure each subject received the optimal clinical dose throughout the study
Oral sustained release tablet, twice or thrice daily. Open label study with active drug, no other intervention arms.
Other Names:
  • UT-15C
  • Treprostinil diethanolamine, treprostinil diolamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Exercise Capacity at Month 12
Time Frame: From First Visit (Visit 1) to Month 12
Assess the effect of continued therapy with oral treprostinil on exercise capacity as assessed by the change from Baseline in 6-Minute Walk Test (6MWT) after 1 year of treatment. The 6MWT is the clinical standard for assessing subject functional status in the treatment of PAH and has been considered an objective measure of subject functional status by the American Thoracic Society. The distance a subject can walk in 6 minutes is recorded in meters.
From First Visit (Visit 1) to Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2007

Primary Completion (Actual)

February 12, 2020

Study Completion (Actual)

February 12, 2020

Study Registration Dates

First Submitted

December 4, 2009

First Submitted That Met QC Criteria

December 8, 2009

First Posted (Estimate)

December 9, 2009

Study Record Updates

Last Update Posted (Actual)

May 10, 2021

Last Update Submitted That Met QC Criteria

April 14, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pulmonary Arterial Hypertension

Clinical Trials on Oral Treprostinil

3
Subscribe