An Open-Label, Long-Term Study of Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension

Open-Label Extension Study of UT-15C in Subjects With Pulmonary Arterial Hypertension- A Long-Term Follow-Up to Protocol TDE-PH-310

This study is an international, multi-center, open-label study designed to provide oral treprostinil (UT-15C) to eligible subjects with pulmonary arterial hypertension who have completed the TDE-PH-310 study. The purpose of this study is to assess the long-term safety of UT-15C and to assess the effects of long-term treatment with UT-15C on exercise capacity.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: UT-15C (treprostinil diolamine)

• Study Type: Interventional
• Enrollment (Actual): 471
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Sanatorio de la Trinidad Mitre
  • Santa Fe, Argentina, S3000EOY
    • Hospital Dr. Jose Maria Cullen
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1425DUH
      • Sanatorio San Jose
  • Distrito Federal
    • Ciudad Autónoma de Buenos Aires, Distrito Federal, Argentina, C1181ACH
      • Hospital Italiano de Buenos Aires
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2001OAD
      • Hospital Italiano Garibaldi
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Kingswood, New South Wales, Australia, 2751
      • Nepean Hospital
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University
    • Sydney, New South Wales, Australia, 2010
      • Saint Vincents Hospital
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Prince Charles Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Austria
  • Wien, Austria, 1090
    • Medizinische Universitat Wien
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Krankenhaus Elisabethinen Linz
• Brazil
  • São Paulo, Brazil, 01323-020
    • Hospital Alemao Oswaldo Cruz
  • Goias
    • Goiania, Goias, Brazil, 74605-050
      • Hospital das Clinicas da Universidade Federal de Goias
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital das Clinicas da Universidade Federal de Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30380-090
      • Hospital Madre Teresa
  • RIO Grande DO SUL
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90020-090
      • Complexo Hospitalar Santa Casa de Porto Alegre
  • SAO Paulo
    • Botucatu, SAO Paulo, Brazil, 18618-970
      • Hospital das Clínicas da Faculdade de Medicina de Botucatu- UNESP
    • São Paulo, SAO Paulo, Brazil, 05403-000
      • Hospital da Clinicas da Faculdade de Medicina da Universidade de São Paulo
    • São Paulo, SAO Paulo, Brazil
      • Escola Paulista de Medicina, Universidade Federal de São Paulo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Respiratory Research Foundation
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Coastal Health
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Lawson Health Research Institute
• Chile
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7500710
      • Centro de Investigaciones TASOL
  • Santiago
    • Vitacura, Santiago, Chile, 7650018
      • Clinica Tabancura
• China
  • Beijing, China, 100853
    • Chinese PLA General Hospital
  • Beijing, China, 100038
    • Beijing Shijitan Hospital
  • Beijing, China, 100005
    • Peking Union Medical College Hospital
  • Qingdao, China, 26603
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China, 200001
    • Renji Hospital of Shanghai Jiaotong University
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital of Tongji University
  • Shenyang, China, 110015
    • Shenyang general hospital of Shenyang military command
  • Beijing
    • Beijing, Beijing, China, 100020
      • Beijing Chao-Yang Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Asia Heart Hospital
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital of Nanjing Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200120
      • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610047
      • West China Hospital
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital, Skejby
  • Copenhagen, Denmark, 2100
    • Rigshospitalet-Copenhagen University Hospital
• France
  • Aquitaine
    • Pessac, Aquitaine, France, 33064
      • Hôpital Haut-Lévêque, CHU Bordeaux
  • Franche-comte
    • Besancon, Franche-comte, France, 25030
      • Hopital Jean Minjoz Centre Hospitalier Universitaire Besancon
  • Languedoc-roussillon
    • Montpellier cedex 5, Languedoc-roussillon, France, 34295
      • CHU de Montpellier
  • Limousin, Lorraine
    • Vandoeuvre-Les-Nancy, Limousin, Lorraine, France, 54500
      • Hôpital Brabois
  • NORD Pas-de-calais
    • Lille, NORD Pas-de-calais, France, 59037
      • Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
  • Provence Alpes COTE D'azur
    • Marseille, Provence Alpes COTE D'azur, France, 13015
      • Centre Hospitalier Universitaire Hôpital Nord
• Germany
  • Hamburg, Germany, 20246
    • Universitätskrankenhaus Hamburg-Eppendorf
  • Baden-wuerttemberg
    • Heidelberg, Baden-wuerttemberg, Germany, 69126
      • Thoraxklinik am Universitatsklinikum Heidelberg
  • Bayern
    • Munchen, Bayern, Germany, 81377
      • Ludwig-Maximilians-Universität München
    • Regensburg, Bayern, Germany, 93053
      • Universitätsklinikum Regensburg
    • Wurzburg, Bayern, Germany, 97074
      • Missionsarztliche Klinik Wurzburg gGmbH
  • Mecklenburg-vorpommern
    • Greifswald, Mecklenburg-vorpommern, Germany, 17475
      • Universitätsmedizin Greifswald
  • Nordrhein-westfalen
    • Bochum, Nordrhein-westfalen, Germany, 44789
      • Bergmannsheil Berufsgenossenschaftliche Universitätsklinik GmbH
    • Duisburg, Nordrhein-westfalen, Germany, 47137
      • Herzzentrum Duisburg
    • Köln, Nordrhein-westfalen, Germany, 50937
      • Universitatsklinikum Koln
  • Rheinland-pfalz
    • Mainz, Rheinland-pfalz, Germany, 55131
      • Universitätsmedizin der Johannes Gutenberg Universität
  • Saarland
    • Homburg, Saarland, Germany, 66424
      • Universitätsklinikum des Saarlandes
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Technische Universität Dresden
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig
• Greece
  • Attica
    • Athens, Attica, Greece, 12462
      • University General Hospital of Attikon
  • Macedoni
    • Thessaloniki, Macedoni, Greece, 57010
      • General Hospital of Thessaloniki, "G.Papanikolaou"
• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500 063
      • Mediciti Hospital
    • Hyderabad, Andhra Pradesh, India, 500 001
      • Care hospital
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Sir Ganga Ram Hospital
    • New Delhi, Delhi, India, 110076
      • Indraprastha Apollo Hospital
  • Gujarat
    • Ahmedabad, Gujarat, India, 38006
      • Care Institute Medical Sciences
    • Gandhinagar, Gujarat, India, 382428
      • Apollo Hospitals International, Ltd.
  • Haryana
    • Gurgaon, Haryana, India, 122 001
      • Medanta - The Medicity
  • Karnataka
    • Bangalore, Karnataka, India, 560 099
      • Narayana Institute of Cardiac Sciences
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • KEM Hospital
    • Mumbai, Maharashtra, India, 400012
      • King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College
    • Pune, Maharashtra, India, 411 001
      • Ruby Hall Clinic
  • Tamil NADU
    • Chennai, Tamil NADU, India, 600006
      • Apollo Hospital
    • Coimbatore, Tamil NADU, India, 641037
      • G. Kuppuswamy Naidu Memorial Hospital
• Israel
  • Haifa, Israel, 34362
    • Carmel Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Corp.
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Petah Tiqwa
    • Petach Tikvah, Petah Tiqwa, Israel, 49100
      • Rabin Medical Center
  • Tel Aviv
    • Tel Hashomer, Tel Aviv, Israel, 52621
      • The Chaim Sheba Medical Center at Tel HaShomer
• Italy
  • Napoli, Italy
    • Azienda Ospedaliera Universitaria
  • Palermo, Italy, 90127
    • Istituto Mediterraneo Trapianti e Terapia Alta Specializzazione (ISMETT)
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico S. Matteo
  • Roma, Italy, 00161
    • Azienda Policlinico Umberto I di Roma
• Korea, Republic of
  • Incheon, Korea, Republic of, 405-760
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System
• Mexico
  • Distrito Federal
    • Tlalpan, Distrito Federal, Mexico, 14080
      • Instituto Nacional de Cardiologia Ignacio Chavez
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64718
      • Unidad de Investigacion Clinica en Medicina S.C.
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Universitair Medisch Centrum Sint Radboud
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1081 HV
      • Vrije Universiteit Medisch Centrum
• Poland
  • Bialystok, Poland, 15276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Krakow, Poland, 61848
    • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K. Marcinkowskiego w Poznaniu
  • Malogoskie, Poland, 31202
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II
  • Otwock, Poland
    • Europejskie Centrum Zdrowia Otwock, Szpital im. Fryderyka Chopina
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital
  • Singapore, Singapore, 168 752
    • National Heart Centre Singapore
• Sweden
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital Solna
  • Vastra Gotaland
    • Göteborg, Vastra Gotaland, Sweden, 413 45
      • Sahlgrenska University Hospital
• Taiwan
  • Kaohsiung, Taiwan, 81362
    • Veterans General Hospital-Kaohsiung
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Tainan CITY
    • Tainan, Tainan CITY, Taiwan, 70403
      • National Cheng Kung University Hospital
• United Kingdom
  • Cambridgshire
    • Papworth Everard, Cambridgshire, United Kingdom, CB3 8RE
      • Papworth Hospital
  • England
    • London, England, United Kingdom, NW3 2QG
      • Royal Free Hospital
    • Newcastle upon Tyne, England, United Kingdom, NE7 7DN
      • Freeman Hospital
    • Sheffield, England, United Kingdom, S10 2JF
      • Royal Hallamshire Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Arizona Pulmonary Specialists, Ltd.
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Fresno, California, United States, 93701
      • University of California, San Francisco-Fresno
    • Los Angeles, California, United States, 90211
      • Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95817
      • University of California-Davis Medical Group, Advanced Lung Disease/Transplant Program
    • Torrance, California, United States, 90502
      • David Geffen School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida College of Medicine Jacksonville- Division of Pulmonary & Critical Medicine
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Augusta, Georgia, United States, 30912
      • Augusta University
    • Austell, Georgia, United States, 30106
      • Piedmont - Georgia Lung Associates
  • Illinois
    • Peoria, Illinois, United States, 61614
      • HeartCare Midwest
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Indiana University Hospital
  • Iowa
    • Iowa City, Iowa, United States, 55242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Troy, Michigan, United States, 48085
      • Beaumont Health
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5990
      • Nebraska Medical Center
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Cardiology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • University Hospital
    • Columbus, Ohio, United States, 43321
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Research Institute
    • Portland, Oregon, United States, 97201-3098
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine, University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center - Presbyterian Cardiovascular Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Cardiovascular Research Institute
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participated in United Therapeutics Study TDE-PH-310
• All women of childbearing potential (WOCBP) must have practiced true abstinence from intercourse when it was in line with their preferred and usual lifestyle or used 2 different forms of highly effective contraception for the duration of the study and for at least 30 days after discontinuing study medication.
• Males who participated in the study must have used a condom during the length of the study and for at least 48 hours after their last dose of study medication.

Exclusion Criteria:

• The subject was pregnant or lactating.
• The subject had received infused or inhaled prostacyclin therapy for 29 days or more.
• The subject was prematurely discontinued from TDE-PH-310 for reasons other than a clinical worsening event.
• The subject developed a concurrent illness or condition during the conduct of TDE-PH-310 which, in the opinion of the Investigator, would represent a risk to their 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: UT-15C; Open label access	Drug: UT-15C (treprostinil diolamine); UT-15C extended release oral tablet three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	All subjects who received oral treprostinil in TDE-PH-311 were included in the Safety population. All AEs were captured from the time the ICF was signed. All AEs were followed until resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for up to 30 days if the AE extended beyond the final visit. All SAEs were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 30 days after completion of the final visit. The overall summary of AEs includes the number of subjects with any AE, the number of subjects with any study drug-related AEs, the number of subjects with AEs leading to study drug withdrawal, the number of subjects with any serious AEs, the number of subjects with any severe AEs, and the number of subjects with any study drug-related severe/serious AEs. AEs were coded using the Medical Dictionary for Regulatory Activities.	Participants will be followed every 12 weeks, at minimum, until they discontinue the study or the study is discontinued by the sponsor or for a period up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-Minute Walk Distance From Baseline	A summary of change from Baseline in 6MWD at Week 48 for the Safety Population is provided. The Safety Population is all subjects who received oral treprostinil in TDE-PH-311.	Baseline to Week 48
Change in Borg Dyspnea Score From Baseline to Week 48	Change in Borg Dyspnea Score from at Week 48 is provided for the Safety Population (all subjects who received oral treprostinil in TDE-PH-311). The Borg Dyspnea Scale is a 0 to 10 rated numerical score used to measure dyspnea as reported by the patient during submaximal exercise and was administered during six-minute walk testing (6MWT), one of the most common and frequently used measures to assess disease severity in PAH. The numbers on the scale are as follows: 0 (no shortness of breath [SOB]), 0.5 (very very slight SOB), 1 (very slight SOB), 3 (moderate SOB), 4 (somewhat severe SOB), 5 (severe SOB), 7 (very severe SOB), 9 (very very severe SOB), 10 (maximal SOB).	Baseline to Week 48
Change From Baseline to Week 48 in WHO Functional Class	Change from Baseline at Week 48 in WHO FC in the Safety Population (all subjects who received oral treprostinil in TDE-PH-311). The World Health Organization functional classification (WHO-FC) is a clinician-rated assessment used widely to assess PAH severity and functioning. Class I (least severe): Patients are without limitation of physical activity. Class II: Patients are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III: Marked limitation of physical activity. They are comfortable at rest. Class IV (most severe): Inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure.	Baseline to Week 48
Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Week 48	Change in N-terminal pro-brain natriuretic peptide from Baseline at Week 48 for the Safety Population (any subject who received oral treprostinil in TDE-PH-311)	Baseline to Week 48

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2013
• Primary Completion (Actual): August 12, 2021
• Study Completion (Actual): August 12, 2021

Study Registration Dates

• First Submitted: March 9, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (Estimate): March 22, 2012

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: PAH; open label; PH; 6 minute walk test; treprostinil; FREEDOM
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-311