An Open-Label Extension Trial of UT-15C Sustained-release (SR) in Subjects With Pulmonary Arterial Hypertension
- Registration Number
- NCT01027949
- Lead Sponsor
- United Therapeutics
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 894
- 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).
- The subject voluntarily gave informed consent to participate in the study.
- 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.
- 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).
- 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.
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Oral Treprostinil 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
- Primary Outcome Measures
Name Time Method Change in Exercise Capacity at Month 12 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (134)
Zentrum für Lungenhochdruck Thoraxklinik am Universitätsklinikum Heidelberg
🇩🇪Hamburg, Germany
Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
🇮🇹Rome, Italy
Unidad de Investigacion Clinica en Medicina S.C.
🇲🇽Monterrey, Mexico
University of California, San Francisco-Fresno
🇺🇸Fresno, California, United States
West Los Angeles VA Healthcare Center
🇺🇸Los Angeles, California, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
The University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Outpatient Center
🇺🇸Baltimore, Maryland, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Presbyterian Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
London Health Sciences Center Victoria Hospital
🇨🇦Toronto, Ontario, Canada
Poona Hospital and Research Centre
🇮🇳Pune, Maharashtra, India
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
The Prince Charles Hospital
🇦🇺Chermside West, Australia
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Brigham and Woman's Hospital
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
UCSD Medical Center
🇺🇸San Diego, California, United States
The Carl and Ethyl Linder Center for Research and Education at the Christ Church
🇺🇸Cincinnati, Ohio, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
University of Minnesota Medical Center, Fairview
🇺🇸Minneapolis, Minnesota, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic Phoenix
🇺🇸Phoenix, Arizona, United States
Arizona Pulmonary Specialists, Ltd.
🇺🇸Phoenix, Arizona, United States
Alexandria Cardiology Clinic
🇺🇸Alexandria, Louisiana, United States
Peter Lougheed Centre
🇨🇦Calgary, Alberta, Canada
Universitaetsklinik für Innere Medizin Innsbruck
🇦🇹Wien, Austria
Life Care Institute of Medical Sciences & Research
🇮🇳Ahmedabad, India
Europejskie Centrum Zdrowia Otwock
🇵🇱Warsaw, Poland
Oddzial Kardiologiczny
🇵🇱Wroclaw, Poland
Care Institute of Medical Sciences
🇮🇳Ahmedabad, Gujarat, India
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Sir Ganga Ram Hospital
🇮🇳New Delhi, India
Rambam Medical Center
🇮🇱Haifa, Israel
Hadassah Hebrew University Medical Center
🇮🇱Jerusalem, Israel
Klinika Chorób Serca i Naczyń, Krakowski Szpital Specjalistyczny im. Jana Pawla II
🇵🇱Kraków, Poland
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Instituto Nacional de Cardiologia
🇲🇽Mexico City, Mexico
Servico de Cardiologia Hospital de Santa Marta
🇵🇹Lisbon, Portugal
Vancouver Coastal Health Authority Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Medical University Graz
🇦🇹Wein, Austria
University Hospital Gasthuisberg
🇧🇪Leuven, Belgium
Sir Mortimer B. Davis Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
G. Kuppuswamy Naidu Memorial Hospital
🇮🇳Coimbatore, India
PRIME Hospitals
🇮🇳Hyderabad, India
Auxilio Mutuo Hospital CardioPulmonary Research Center
🇵🇷Guaynabo, Puerto Rico
The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
Legacy Pulmonary Clinic
🇺🇸Portland, Oregon, United States
Oregon Health and Sciences University
🇺🇸Portland, Oregon, United States
Policlinico S. Orsola Malpighi - Università degli studi di Bologna
🇮🇹Bologna, Italy
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Aurora Cardiovascular Services
🇺🇸Milwaukee, Wisconsin, United States
University of Colorado Health Science Center
🇺🇸Aurora, Colorado, United States
The Children's Hospital
🇺🇸Aurora, Colorado, United States
University of Arizona Clinical and Translational Science (CATS) Research Center
🇺🇸Tucson, Arizona, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Stanford University, Pulmonary and Critical Care Medicine
🇺🇸Stanford, California, United States
University of Florida College of Medicine Jacksonville
🇺🇸Jacksonville, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Kentuckiana Pulmonary Associates
🇺🇸Louisville, Kentucky, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Mary Parkes Center
🇺🇸Rochester, New York, United States
University of North Carolina Hospitals
🇺🇸Chapel Hill, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
The University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Medical School
🇺🇸Houston, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Heart/Lung Transplant Unit - St. Vincent's Hospital
🇦🇺Darlinghurst, Australia
The Alfred Hospital
🇦🇺Melbourne, Australia
Royal Perth Hospital
🇦🇺Perth, Australia
Medizininische Universitaet Wien
🇦🇹Wien, Austria
Department of Cardiology Erasme University Hospital
🇧🇪Brussels, Belgium
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Beijing Shijitan Hospital, Cadres Respiratory Department
🇨🇳Beijing, China
Peking Union Medical College Hospital, Respiratory Medicine Department
🇨🇳Beijing, China
Service Chirurgie Thoracique, Hôpital Haut Levêque
🇫🇷Pessac, Pessac Cedex, France
Shanghai Pulmonary Hospital, Respiratory Medicine Department
🇨🇳Shanghai, China
Centre d'Investigation Clinique Hôpital La Cavale Blanche - CHU Brest
🇫🇷Brest, France
PMAC, Clinique de Pneumologie
🇫🇷Bernin, France
Hospital Antoine Beclere
🇫🇷Clamart, France
Hôpital Louis Pradel
🇫🇷Lyon, France
Hospital Claude Huriez
🇫🇷Lille Cedex, France
CHU Arnaud de Villeneuve - Service maladies respiratoires
🇫🇷Montpellier cedex 5, France
Universitätsklinikum Dresden Abtl. Pneumologie
🇩🇪Dresden, Germany
Service de Pneumologie Centre de Competence pour l'HTAP- Pole des Voies Respiratoires Hôpital Larrey
🇫🇷Toulouse, France
University Hospital Greifswald
🇩🇪Greifswald, Germany
Universitatsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
DRK Kliniken Berlin Köpenick
🇩🇪Hamburg, Germany
Universitätsklinkium Köln Klinik III für Innere Medizin
🇩🇪Hamburg, Germany
Medizinische Hochschule Hannover (MHH)
🇩🇪Hannover, Germany
Dept. of Internal Medicine III University Heidelberg
🇩🇪Heidelberg, Germany
Narayana Hrudayalaya Hospitals
🇮🇳Bangalore, Karnataka, India
Sri Ramachandra Medical College & Research Institute
🇮🇳Chennai, India
Asian Heart Institute & Research Centre Pvt. Ltd.
🇮🇳Mumbai, Maharashtra, India
Queen's NRI Hospital
🇮🇳Visakhapatnam, India
Pulmonary Hypertension Unit Centre for Lung Health Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
The Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Pulmonary Institute Rabin Medical Center (Belinson Kampus)
🇮🇱Petah Tiqva, Israel
Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.
🇮🇹Napoli, Italy
Pulmonary Institute Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Hospital Universitario de la UANL
🇲🇽Monterrey, Mexico
Radboud University Nijmegen Medical Center
🇳🇱Amsterdam, Netherlands
VU Medish Centrum
🇳🇱Amsterdam, Netherlands
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Freeman Hospital
🇬🇧Newcastle, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Skane University Hospital
🇸🇪Lund, Sweden
Hospital Clínic I Provincial
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Papworth Hospital
🇬🇧Cambridge, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Papworth Hospital NHS Foundation Trust
🇬🇧Glasgow, United Kingdom
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
University Medical Center
🇺🇸Tucson, Arizona, United States
Ruby Hall Clinic
🇮🇳Pune, India
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States