Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension
- Registration Number
- NCT00887978
- Lead Sponsor
- United Therapeutics
- Brief Summary
This study is an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who are currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor). Study visits will occur at 4 week intervals for 16 weeks with the key measure of efficacy being the 6-minute walk test. Study procedures include routine blood tests, medical history, physical exams, disease evaluation, and exercise tests.
Patients who complete all assessments for 16-weeks will also be eligible to enter an open-label, extension phase study (FREEDOM - EXT).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 310
- A subject is eligible for inclusion in this study if all of the following criteria apply:
- Between 18 and 75 years of age, inclusive.
- Body weight at least 40 kg (approximately 90 lbs.)
- PAH that is either idiopathic/heritable; associated with appetite suppressant or toxin use; associated with collagen vascular disease; associated with repaired congenital shunts; associated with HIV.
- Currently receiving an approved endothelin receptor antagonist and/or an approved phosphodiesterase-5 inhibitor for at least 90 days and on a stable dose for at least the last 30 days.
- Baseline six-minute walk distance (6MWD) between 150-425 meters
- Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
- Reliable and cooperative with protocol requirements.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Identical placebo tablets to UT-15C, doses were titrated in the same manner UT-15C SR UT-15C SR Doses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID.
- Primary Outcome Measures
Name Time Method 6-minute Walk Distance (6MWD) Baseline and 16 weeks Placebo-corrected change in 6MWD from Baseline to Week 16, correlates with the current clinical standard for assessing patient functional status in the treatment of PAH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS).
The 6MWD was to be assessed between 3 and 6 hours after the morning dose of study drug and background therapy(ies).
- Secondary Outcome Measures
Name Time Method Clinical Worsening Assessment Baseline and 16 Weeks Definition of clinical worsening included patients who met at least one of the following criteria during the 16 weeks of study:
1. Death (all causes excluding accident)
2. Transplantation
3. Atrial septostomy
4. Hospitalization as a result of right heart failure
5. Greater than or equal to a 20% decrease in 6MWD from Baseline (or too ill to walk) AND addition of an inhaled prostacyclin analogue, ERA, or PDE-5i
6. Initiation of parenteral prostacyclin therapy (i.e., epoprostenol, iloprost, or treprostinil) for the treatment of PAHBorg Dyspnea Score Baseline and 16 Weeks The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).
World Health Organization (WHO) Functional Class Baseline and 16 Weeks Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
Symptoms of PAH Baseline and 16 Weeks Symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea were assessed by the physician at Baseline and Week 16. Severity grade values (i.e., 0, 1, 2 or 3) for each symptom were provided each subject. A severity of 0 indicated no symptoms, the maximum severity was 3, indicating severe symptoms. Mean change in symptom severity from Baseline to Week 16 is described.
Dyspnea Fatigue Index Baseline and 16 Weeks The dyspnea-fatigue index was assessed at Baseline and Week 16. Each of the three components of the dyspnea-fatigue index were rated on a scale 0 to 4, with 0 being the worst condition and 4 being the best condition for each component. The dyspnea-fatigue index is computed by summing the three component scores.
N-terminal proBNP (NT-proBNP) Baseline and 16 Weeks Serum N-terminal pro-BNP concentration was assessed at Baseline and Week 16.
Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Baseline and 16 Weeks Change in CAMPHOR Scores from Baseline to Week 16. The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning)and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.
Trial Locations
- Locations (62)
Washington University Hospital
🇺🇸St. Louis, Missouri, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Pulmonary Critical Care Medicine, Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Lindner Center
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University Hospitals Case Medical Center
🇺🇸Cleveland, Ohio, United States
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Colorado Health Science Center
🇺🇸Aurora, Colorado, United States
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
Arizona Pulmonary Specialist, LTD
🇺🇸Phoenix, Arizona, United States
UCSD Medical Center
🇺🇸La Jolla, California, United States
UT Southwestern
🇺🇸Dallas, Texas, United States
University of Alabama-Birmingham
🇺🇸Birmingham, Alabama, United States
West Los Angeles VA Healthcare Center
🇺🇸Los Angeles, California, United States
Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
University of California, San Francisco-Fresno
🇺🇸Fresno, California, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
University of Florida-Jacksonville
🇺🇸Jacksonville, Florida, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Kentuckiana Pulmonary Associates
🇺🇸Louisville, Kentucky, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Mary M Parkes Center for Asthma, Allergy and Pulmonary Care
🇺🇸Rochester, New York, United States
Columbia University Presbyterian Medical Center
🇺🇸New York, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Legacy Pulmonary Northwest
🇺🇸Portland, Oregon, United States
The University of Toledo
🇺🇸Toledo, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
OHSU
🇺🇸Portland, Oregon, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
University of Alberta Hospitals
🇨🇦Edmonton, Alberta, Canada
Vancouver Coastal Health Respiratory Clinic
🇨🇦Vancouver, British Columbia, Canada
London Health Sciences Center
🇨🇦London, Ontario, Canada
University of Calgary
🇨🇦Calgary, Alberta, Canada
University Hospital Gasthuisberg
🇧🇪Leuven, Belgium
Inova Transplant Center
🇺🇸Falls Church, Virginia, United States
Hospital Claude Huriez
🇫🇷Lille, Cedex, France
Hospital Cavale Blanche
🇫🇷Brest, France
Universitaetsklinikum Dresden
🇩🇪Dresden, Germany
Hospital Haut Leveque
🇫🇷Pessac, Cedex, France
Azienda Ospedaliera Universitaria
🇮🇹Naples, Italy
Lady Davis Carmel Medical Centre
🇮🇱Haifa, Israel
University Hospital Greifswald
🇩🇪Greifswald, Germany
Pulmonology Department Rambam Medical Center
🇮🇱Haifa, Israel
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Pulmonary institute
🇮🇱Ramat Gan, Israel
VUMC
🇳🇱Amsterdam, Netherlands
Hospital de Santa Marta
🇵🇹Lisboa, Portugal
Hospital Clinic I Provincial de Barcelona
🇪🇸Barcelona, Spain
Lund University Hospital
🇸🇪Lund, Sweden
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Royal Free Hospital NHS Trust
🇬🇧London, United Kingdom