FREEDOM-C: Oral Treprostinil in Combination With an Endothelin Receptor Antagonist (ERA) and/or a Phosphodiesterase-5 (PDE-5) Inhibitor for the Treatment of Pulmonary Arterial Hypertension (PAH)
- Conditions
- Pulmonary Hypertension
- Interventions
- Drug: PlaceboDrug: Oral treprostinil (UT-15C) sustained release tablets
- Registration Number
- NCT00325442
- Lead Sponsor
- United Therapeutics
- Brief Summary
This study was an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who were currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor). Study visits occurred at 4 week intervals for 16 weeks; the key measure of efficacy was the 6-minute walk test. Study procedures included routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. One optional substudy was also a part of FREEDOM-C at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 16.
Patients who completed all assessments for 16-weeks were also eligible to enter an open-label, extension phase study (FREEDOM - EXT).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 354
- Between 12 and 70 years of age, inclusive.
- Body weight at least 45 kg (approximately 100 pounds).
- PAH that is either idiopathic/heritable (including PAH associated with appetite suppressant/toxin use); PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); PAH associated with collagen vascular disease; or PAH associated with HIV.
- Baseline 6-minute walk distance between 150 and 450 meters, inclusive.
- 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.
- Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
- Reliable and cooperative with protocol requirements.
- Nursing or pregnant.
- Received a prostacyclin within the past 30 days.
- PAH due to conditions other than noted in the above inclusion criteria.
- History of uncontrolled sleep apnea, renal insufficiency, anemia, left sided heart disease, uncontrolled systemic hypertension, or parenchymal lung disease.
- Use of an investigational drug within 30 days of Baseline.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Arm Placebo Subjects assigned to placebo 0.25, 0.5, 1, or 5 mg oral tablets. Active Oral treprostinil (UT-15C) sustained release tablets Subjects assigned to active therapy with UT-15C 0.25, 0.5, 1, or 5 mg oral tablets.
- Primary Outcome Measures
Name Time Method Six Minute Walk Distance (6MWD) Baseline and 16 Weeks Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 16, correlates with the historical 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 six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug.
- Secondary Outcome Measures
Name Time Method Borg Dyspnea Score Baseline and 16 Weeks The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6-minute walk test. The Borg dyspnea score was assessed immediately following the 6-minute walk test. Scores ranged from 0 (for no shortness of breath) to 10 (for greatest shortness of breath ever experienced).
Clinical Worsening Assessment Baseline and 16 Weeks Definition of clinical worsening required one of the following:
1. Death (all causes excluding accident)
2. Transplantation or atrial septostomy
3. Clinical deterioration as defined by:
1. Hospitalization as a result of PAH, or
2. ≥ 20% decrease in 6-minute walk distance from Baseline (or too ill to walk) and a decrease in WHO functional class And
3. Initiation of new PAH specific therapy (i.e., ERA, PDE5I, prostacyclin).Dyspnea-Fatigue Index Baseline and 16 Weeks The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.
World Health Organization Functional Classification for PAH Week 16 Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope.
Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. These patients are comfortable at rest, but ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope.
Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope.
Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present even at rest. Discomfort is increased by any physical activity.Six Minute Walk Distance (6MWD) Baseline and 4 weeks Placebo corrected change in six minute walk distance (6MWD) from Baseline to Week 4, correlates with the historical 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 six minute walk test was to be conducted 3 to 6 hours after the previous dose of study drug.Change in Symptoms of PAH From Baseline to Week 16 Baseline and 16 weeks Defined symptoms of PAH including fatigue, dyspnea, edema, dizziness, syncope, chest pain, and orthopnea were assessed at Baseline prior to starting study drug and during the Treatment Phase at Week 16. Severity grade values (i.e., 0, 1, 2, or 3 in increasing severity) were assigned for each symptom. The outcome data describes the change in severity values from Baseline to Week 16 for each defined symptom of PAH.
Trial Locations
- Locations (72)
SMBD Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
UT Southwestern
🇺🇸Dallas, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Stanford University, Pulmonary and Critical Care
🇺🇸Palo Alto, California, United States
Harbour-UCLA Medical Center
🇺🇸Torrance, California, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa Health Care
🇺🇸Iowa, Iowa, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Columbia Presbyterian Medical Center
🇺🇸New York, New York, United States
Washington University Hospital
🇺🇸Saint Louis, Missouri, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Mary M Parkes Center for Asthma, Allergy and Pulmonary Care
🇺🇸Rochester, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Baylor College of Medicine, Pulmonary & Critical Care
🇺🇸Houston, Texas, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Inova Transplant Center
🇺🇸Fairfax, Virginia, United States
Royal Perth Hospital
🇦🇺Perth, Australia
St. Vincent's Hospital
🇦🇺Sydney, New South Wales, Australia
The Prince Charles Hospital
🇦🇺Brisbane, Australia
Universitaet Wien
🇦🇹Wien, Austria
University Hospital Gasthuisberg
🇧🇪Leuven, Belgium
Lab London Health Sciences Center
🇨🇦London, Ontario, Canada
Respiratory Research
🇨🇦Calgary, Alberta, Canada
Hospital Claude Huriez
🇫🇷Lille Cedex, France
Hospital Cavale Blanche
🇫🇷Brest, France
Hôpital Louis Pradel
🇫🇷Lyon, France
Hospital Antoine Beclere
🇫🇷Clamart, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Mater Misericordiae University Hospital Ltd
🇮🇪Dublin, Ireland
Hadassah Ein-Kerem Medical Center
🇮🇱Jerusalem, Israel
Tel Hashomer Medical Center
🇮🇱Ramat Gan, Israel
Rabin Medical Center
🇮🇱Petach Tikva, Israel
Universita degli Studi Bologna
🇮🇹Bologna, Italy
Universita "La Sapienza" Roma
🇮🇹Rome, Italy
National Tuberculosis and Lung Disease Research Institute
🇵🇱Warsaw, Poland
Hospital Vrije Universiteit
🇳🇱Amsterdam, Netherlands
Hospital Clinic of Barcelona
🇪🇸Barcelona, Spain
Papworth Hospital
🇬🇧Cambridge, United Kingdom
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Royal Free Hospital
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle, United Kingdom
Maine Medical Center
🇺🇸Portland, Maine, United States
University of Arizona Health Science Center
🇺🇸Tucson, Arizona, United States
John's Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Western Infirmary
🇬🇧Glasgow, United Kingdom
West Los Angeles VA Healthcare Center
🇺🇸Los Angeles, California, United States
Hospital Valle Hebron
🇪🇸Barcelona, Spain
Hospital Erasme
🇧🇪Brussels, Belgium
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Vancouver Coastal Health Respiratory Clinic
🇨🇦Vancouver, British Columbia, Canada
The Alfred Hospital
🇦🇺Melbourne, Australia
Arizona Pulmonary Specialist
🇺🇸Phoenix, Arizona, United States
University of Alabama-Birmingham
🇺🇸Birmingham, Alabama, United States
University of California-San Francisco
🇺🇸San Francisco, California, United States
The Children's Hospital
🇺🇸Aurora, Colorado, United States
Pulmonary Hypertension Clinic
🇺🇸Aurora, Colorado, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Legacy Clinic Northwest
🇺🇸Portland, Oregon, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, 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
Heart Care Associates
🇺🇸Milwaukee, Wisconsin, United States
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria