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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01560637
• Other study ID #: TDE-PH-311
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2013
• Est. completion date: August 12, 2021

Study information

• Verified date: May 2022
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 471
• Est. completion date: August 12, 2021
• Est. primary completion date: August 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• UT-15C (treprostinil diolamine)
UT-15C extended release oral tablet three times daily

Locations

Country	Name	City	State
Argentina	Sanatorio de la Trinidad Mitre	Buenos Aires
Argentina	Sanatorio San José	Caba	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autónoma de Buenos Aires	Distrito Federal
Argentina	Hospital Italiano Garibaldi	Rosario	Santa Fe
Argentina	Hospital Dr. José María Cullen	Santa Fe
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Prince Charles Hospital	Chermside	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Macquarie University	Sydney	New South Wales
Australia	Saint Vincents Hospital	Sydney	New South Wales
Austria	Krankenhaus Elisabethinen Linz	Linz	Upper Austria
Austria	Medizinische Universität Wien	Wien
Brazil	Hospital das Clínicas da Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais
Brazil	Hospital Madre Teresa	Belo Horizonte	Minas Gerais
Brazil	Hospital das Clínicas da Faculdade de Medicina de Botucatu- UNESP	Botucatu	SAO Paulo
Brazil	Hospital das Clinicas da Universidade Federal de Goias	Goiania	Goias
Brazil	Complexo Hospitalar Santa Casa de Porto Alegre	Porto Alegre	RIO Grande DO SUL
Brazil	Escola Paulista de Medicina, Universidade Federal de São Paulo	São Paulo	SAO Paulo
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Brazil	Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo	SAO Paulo
Canada	Respiratory Research Foundation	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Lawson Health Research Institute	London	Ontario
Canada	Vancouver Coastal Health	Vancouver	British Columbia
Chile	Centro de Investigaciones TASOL	Santiago	Region Metropolitana
Chile	Clínica Tabancura	Vitacura	Santiago
China	Beijing Chao-Yang Hospital	Beijing	Beijing
China	Beijing Shijitan Hospital	Beijing
China	Chinese PLA General Hospital	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Xiangya Hospital	Changsha	Hunan
China	West China Hospital	Chengdu	Sichuan
China	Guangdong General Hospital	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Nanchang Medical University	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao
China	Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Renji Hospital of Shanghai Jiaotong University	Shanghai
China	Shanghai Pulmonary Hospital of Tongji University	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	Shenyang General Hospital of Shenyang Military Command	Shenyang
China	Wuhan Asia Heart Hospital	Wuhan	Hubei
Denmark	Aarhus Universitetshospital, Skejby	Aarhus
Denmark	Rigshospitalet-Copenhagen University Hospital	Copenhagen
France	Hopital Jean Minjoz Centre Hospitalier Universitaire Besancon	Besancon	Franche-comte
France	Centre Hospitalier Régional Universitaire de Lille - Hôpital Claude Huriez	Lille	NORD Pas-de-calais
France	Centre Hospitalier Universitaire Hopital Nord	Marseille	Provence Alpes COTE D'azur
France	CHU de Montpellier	Montpellier cedex 5	Languedoc-roussillon
France	Hopital Haut-Leveque, CHU Bordeaux	Pessac	Aquitaine
France	Hopital Brabois	Vandoeuvre-Les-Nancy	Limousin, Lorraine
Germany	Bergmannsheil Berufsgenossenschaftliche Universitätsklinik GmbH	Bochum	Nordrhein-westfalen
Germany	Technische Universität Dresden	Dresden	Sachsen
Germany	Herzzentrum Duisburg	Duisburg	Nordrhein-westfalen
Germany	Universitätsmedizin Greifswald	Greifswald	Mecklenburg-vorpommern
Germany	Universitätskrankenhaus Hamburg-Eppendorf	Hamburg
Germany	Thoraxklinik am Universitätsklinikum Heidelberg	Heidelberg	Baden-wuerttemberg
Germany	Universitätsklinikum des Saarlandes	Homburg	Saarland
Germany	Universitätsklinikum Köln	Köln	Nordrhein-westfalen
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsmedizin der Johannes Gutenberg Universität	Mainz	Rheinland-pfalz
Germany	Ludwig-Maximilians-Universitat Munchen	Munchen	Bayern
Germany	Universitätsklinikum Regensburg	Regensburg	Bayern
Germany	Missionsarztliche Klinik Wurzburg gGmbH	Wurzburg	Bayern
Greece	University General Hospital of Attikon	Athens	Attica
Greece	General Hospital of Thessaloniki, "G.Papanikolaou"	Thessaloniki	Macedoni
India	Care Institute Medical Sciences	Ahmedabad	Gujarat
India	Narayana Institute of Cardiac Sciences	Bangalore	Karnataka
India	Apollo Hospital	Chennai	Tamil NADU
India	G. Kuppuswamy Naidu Memorial Hospital	Coimbatore	Tamil NADU
India	Apollo Hospitals International, Ltd.	Gandhinagar	Gujarat
India	Medanta - The Medicity	Gurgaon	Haryana
India	CARE Hospital	Hyderabad	Andhra Pradesh
India	Mediciti Hospital	Hyderabad	Andhra Pradesh
India	KEM Hospital	Mumbai	Maharashtra
India	King Edward Memorial Hospital & Seth Gordhandas Sunderdas Medical College	Mumbai	Maharashtra
India	Indraprastha Apollo Hospital	New Delhi	Delhi
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	Ruby Hall Clinic	Pune	Maharashtra
Israel	Carmel Medical Center	Haifa
Israel	Rambam Health Corp.	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikvah	Petah Tiqwa
Israel	The Chaim Sheba Medical Center at Tel Hashomer	Tel Hashomer	Tel Aviv
Italy	Azienda Ospedaliera Universitaria	Napoli
Italy	Istituto Mediterraneo Trapianti e Terapia Alta Specializzazione (ISMETT)	Palermo
Italy	Fondazione IRCCS Policlinico S. Matteo	Pavia
Italy	Azienda Policlinico Umberto I di Roma	Roma
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Unidad de Investigacion Clinica en Medicina S.C.	Monterrey	Nuevo LEON
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Tlalpan	Distrito Federal
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam	Noord-holland
Netherlands	Universitair Medisch Centrum Sint Radboud	Nijmegen	Gelderland
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok
Poland	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K. Marcinkowskiego w Poznaniu	Krakow
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II	Malogoskie
Poland	Europejskie Centrum Zdrowia Otwock, Szpital im. Fryderyka Chopina	Otwock
Singapore	National Heart Centre Singapore	Singapore
Singapore	National University Hospital	Singapore
Sweden	Sahlgrenska University Hospital	Göteborg	Vastra Gotaland
Sweden	Karolinska University Hospital Solna	Stockholm
Taiwan	Veterans General Hospital-Kaohsiung	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan	Tainan CITY
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Royal Free Hospital	London	England
United Kingdom	Freeman Hospital	Newcastle upon Tyne	England
United Kingdom	Papworth Hospital	Papworth Everard	Cambridgshire
United Kingdom	Royal Hallamshire Hospital	Sheffield	England
United States	Asheville Cardiology Associates	Asheville	North Carolina
United States	Emory University Hospital	Atlanta	Georgia
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Piedmont - Georgia Lung Associates	Austell	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Indiana University Hospital	Carmel	Indiana
United States	University of Cincinnati	Cincinnati	Ohio
United States	University Hospital	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	University of California, San Francisco-Fresno	Fresno	California
United States	University of Florida	Gainesville	Florida
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Florida College of Medicine Jacksonville- Division of Pulmonary & Critical Medicine	Jacksonville	Florida
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Kentuckiana Pulmonary Associates	Louisville	Kentucky
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Sentara Cardiovascular Research Institute	Norfolk	Virginia
United States	Nebraska Medical Center	Omaha	Nebraska
United States	HeartCare Midwest	Peoria	Illinois
United States	Perelman Center for Advanced Medicine, University of Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona Pulmonary Specialists, Ltd.	Phoenix	Arizona
United States	University of Pittsburgh Medical Center - Presbyterian Cardiovascular Institute	Pittsburgh	Pennsylvania
United States	Legacy Research Institute	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester	Rochester	New York
United States	University of California-Davis Medical Group, Advanced Lung Disease/Transplant Program	Sacramento	California
United States	David Geffen School of Medicine	Torrance	California
United States	Beaumont Health	Troy	Michigan
United States	University of Arizona	Tucson	Arizona
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  Denmark,  France,  Germany,  Greece,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Singapore,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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