Clinical trial NCT01027949: An Open-Label Extension Trial of UT-15C Sustained-release (SR) in Subjects With Pulmonary Arterial Hypertension
Official title: An Open-Label Extension Trial of UT-15C SR in Subjects With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-12-09
Enrollment: 894
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Exercise Capacity at Month 12
timeFrame: From First Visit (Visit 1) to Month 12
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists, Ltd.
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: University Medical Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Clinical and Translational Science (CATS) Research Center
state: Arizona
city: Fresno
country: United States
facility: University of California, San Francisco-Fresno
state: California
city: Los Angeles
country: United States
facility: West Los Angeles VA Healthcare Center
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University, Pulmonary and Critical Care Medicine
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Health Science Center
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida College of Medicine Jacksonville
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Hospitals
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: Alexandria
country: United States
facility: Alexandria Cardiology Clinic
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Woman's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Mary Parkes Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Carl and Ethyl Linder Center for Research and Education at the Christ Church
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: The University of Toledo Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Pulmonary Clinic
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Presbyterian Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas Medical School
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Aurora Cardiovascular Services
state: Wisconsin
city: Chermside West
country: Australia
facility: The Prince Charles Hospital
city: Darlinghurst
country: Australia
facility: Heart/Lung Transplant Unit - St. Vincent's Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Wein
country: Austria
facility: Medical University Graz
city: Wien
country: Austria
facility: Medizininische Universitaet Wien
city: Wien
country: Austria
facility: Universitaetsklinik für Innere Medizin Innsbruck
city: Brussels
country: Belgium
facility: Department of Cardiology Erasme University Hospital
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Coastal Health Authority Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: London Health Sciences Center Victoria Hospital
state: Ontario
city: Montréal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Beijing
country: China
facility: Beijing Shijitan Hospital, Cadres Respiratory Department
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Respiratory Medicine Department
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital, Respiratory Medicine Department
city: Pessac
country: France
facility: Service Chirurgie Thoracique, Hôpital Haut Levêque
state: Pessac Cedex
city: Bernin
country: France
facility: PMAC, Clinique de Pneumologie
city: Brest
country: France
facility: Centre d'Investigation Clinique Hôpital La Cavale Blanche - CHU Brest
city: Clamart
country: France
facility: Hospital Antoine Beclere
city: Lille Cedex
country: France
facility: Hospital Claude Huriez
city: Lyon
country: France
facility: Hôpital Louis Pradel
city: Montpellier cedex 5
country: France
facility: CHU Arnaud de Villeneuve - Service maladies respiratoires
city: Toulouse
country: France
facility: Service de Pneumologie Centre de Competence pour l'HTAP- Pole des Voies Respiratoires Hôpital Larrey
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden Abtl. Pneumologie
city: Greifswald
country: Germany
facility: University Hospital Greifswald
city: Hamburg
country: Germany
facility: DRK Kliniken Berlin Köpenick
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Hamburg
country: Germany
facility: Universitätsklinkium Köln Klinik III für Innere Medizin
city: Hamburg
country: Germany
facility: Zentrum für Lungenhochdruck Thoraxklinik am Universitätsklinikum Heidelberg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
city: Heidelberg
country: Germany
facility: Dept. of Internal Medicine III University Heidelberg
city: Ahmedabad
country: India
facility: Care Institute of Medical Sciences
state: Gujarat
city: Bangalore
country: India
facility: Narayana Hrudayalaya Hospitals
state: Karnataka
city: Mumbai
country: India
facility: Asian Heart Institute & Research Centre Pvt. Ltd.
state: Maharashtra
city: Pune
country: India
facility: Poona Hospital and Research Centre
state: Maharashtra
city: Ahmedabad
country: India
facility: Life Care Institute of Medical Sciences & Research
city: Chennai
country: India
facility: Sri Ramachandra Medical College & Research Institute
city: Coimbatore
country: India
facility: G. Kuppuswamy Naidu Memorial Hospital
city: Hyderabad
country: India
facility: PRIME Hospitals
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Visakhapatnam
country: India
facility: Queen's NRI Hospital
city: Dublin
country: Ireland
facility: Pulmonary Hypertension Unit Centre for Lung Health Mater Misericordiae University Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: The Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Medical Center
city: Petah Tiqva
country: Israel
facility: Pulmonary Institute Rabin Medical Center (Belinson Kampus)
city: Ramat Gan
country: Israel
facility: Pulmonary Institute Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Policlinico S. Orsola Malpighi - Università degli studi di Bologna
city: Naples
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale Monaldi - Cotugno-CTO Cardiologia S.U.N.
city: Rome
country: Italy
facility: Dipartimento di Scienze Cardiovascolari, Respiratorie e Morfologiche
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia
city: Monterrey
country: Mexico
facility: Hospital Universitario de la UANL
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina S.C.
city: Amsterdam
country: Netherlands
facility: Radboud University Nijmegen Medical Center
city: Amsterdam
country: Netherlands
facility: VU Medish Centrum
city: Kraków
country: Poland
facility: Klinika Chorób Serca i Naczyń, Krakowski Szpital Specjalistyczny im. Jana Pawla II
city: Warsaw
country: Poland
facility: Europejskie Centrum Zdrowia Otwock
city: Wroclaw
country: Poland
facility: Oddzial Kardiologiczny
city: Lisbon
country: Portugal
facility: Servico de Cardiologia Hospital de Santa Marta
city: Guaynabo
country: Puerto Rico
facility: Auxilio Mutuo Hospital CardioPulmonary Research Center
city: Barcelona
country: Spain
facility: Hospital Clínic I Provincial
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Lund
country: Sweden
facility: Skane University Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
city: Glasgow
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
References: