Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension (FREEDOM-C2)
This study has been completed.
Sponsor:
United Therapeutics
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00887978
First received: April 23, 2009
Last updated: December 7, 2012
Last verified: December 2012
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Pulmonary Hypertension |
Drug: UT-15C SR Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension |
Resource links provided by NLM:
Further study details as provided by United Therapeutics:
Primary Outcome Measures:
- 6-minute Walk Distance (6MWD) [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
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:
- Clinical Worsening Assessment [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: Yes ]
Definition of clinical worsening included patients who met at least one of the following criteria during the 16 weeks of study:
- Death (all causes excluding accident)
- Transplantation
- Atrial septostomy
- Hospitalization as a result of right heart failure
- 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
- Initiation of parenteral prostacyclin therapy (i.e., epoprostenol, iloprost, or treprostinil) for the treatment of PAH
- Borg Dyspnea Score [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]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 [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]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) [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]Serum N-terminal pro-BNP concentration was assessed at Baseline and Week 16.
- Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) [ Time Frame: Baseline and 16 Weeks ] [ Designated as safety issue: No ]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.
| Enrollment: | 310 |
| Study Start Date: | June 2009 |
| Study Completion Date: | July 2011 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Placebo
Identical placebo tablets to UT-15C, doses were titrated in the same manner
|
Drug: Placebo |
|
Experimental: 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.
|
Drug: UT-15C SR
treprostinil diolamine sustained release tablets
Other Name: treprostinil diolamine, treprostinil diethanolamine, UT-15C
|
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00887978
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Hide Study LocationsLocations
| United States, Alabama | |
| University of Alabama-Birmingham | |
| Birmingham, Alabama, United States, 35294-0006 | |
| United States, Arizona | |
| Arizona Pulmonary Specialist, LTD | |
| Phoenix, Arizona, United States, 85013 | |
| United States, California | |
| University of California, San Francisco-Fresno | |
| Fresno, California, United States, 93701 | |
| UCSD Medical Center | |
| La Jolla, California, United States, 92037 | |
| West Los Angeles VA Healthcare Center | |
| Los Angeles, California, United States, 90073 | |
| UC Davis Medical Center | |
| Sacramento, California, United States, 95817 | |
| Harbor-UCLA Medical Center | |
| Torrance, California, United States, 90502 | |
| United States, Colorado | |
| University of Colorado Health Science Center | |
| Aurora, Colorado, United States, 80045 | |
| United States, Florida | |
| University of Florida-Jacksonville | |
| Jacksonville, Florida, United States, 32209 | |
| Cleveland Clinic Florida | |
| Weston, Florida, United States, 33331 | |
| United States, Georgia | |
| Emory University School of Medicine | |
| Atlanta, Georgia, United States, 30322 | |
| United States, Illinois | |
| University of Chicago Hospitals | |
| Chicago, Illinois, United States, 60637 | |
| United States, Iowa | |
| University of Iowa Hospitals and Clinics | |
| Iowa City, Iowa, United States, 52242 | |
| United States, Kansas | |
| Kansas University Medical Center | |
| Kansas City, Kansas, United States, 66160 | |
| United States, Kentucky | |
| Kentuckiana Pulmonary Associates | |
| Louisville, Kentucky, United States, 40202 | |
| United States, Maine | |
| Maine Medical Center | |
| Portland, Maine, United States, 04102-3175 | |
| United States, Massachusetts | |
| Pulmonary Critical Care Medicine, Brigham and Women's Hospital | |
| Boston, Massachusetts, United States, 02115 | |
| Tufts Medical Center | |
| Boston, Massachusetts, United States, 02111 | |
| United States, Minnesota | |
| Mayo Clinic | |
| Rochester, Minnesota, United States, 55902 | |
| United States, Missouri | |
| Washington University Hospital | |
| St. Louis, Missouri, United States, 63110-1093 | |
| United States, Nebraska | |
| University of Nebraska Medical Center | |
| Omaha, Nebraska, United States, 68198-5300 | |
| United States, New Jersey | |
| Newark Beth Israel Medical Center | |
| Newark, New Jersey, United States, 07112 | |
| United States, New York | |
| Winthrop University Hospital | |
| Mineola, New York, United States, 11501 | |
| Columbia University Presbyterian Medical Center | |
| New York, New York, United States, 10032 | |
| Mary M Parkes Center for Asthma, Allergy and Pulmonary Care | |
| Rochester, New York, United States, 14623 | |
| United States, North Carolina | |
| Duke University Medical Center | |
| Durham, North Carolina, United States, 27710 | |
| United States, Ohio | |
| Lindner Center | |
| Cincinnati, Ohio, United States, 45219 | |
| University of Cincinnati | |
| Cincinnati, Ohio, United States, 45267-0564 | |
| University Hospitals Case Medical Center | |
| Cleveland, Ohio, United States, 44106 | |
| Ohio State University | |
| Columbus, Ohio, United States, 43210 | |
| The University of Toledo | |
| Toledo, Ohio, United States, 43614 | |
| United States, Oregon | |
| Legacy Pulmonary Northwest | |
| Portland, Oregon, United States, 97210 | |
| OHSU | |
| Portland, Oregon, United States, 97239 | |
| United States, Pennsylvania | |
| University of Pennsylvania | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| University of Pittsburgh Medical Center | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| Allegheny General Hospital | |
| Pittsburgh, Pennsylvania, United States, 15212 | |
| United States, Texas | |
| UT Southwestern | |
| Dallas, Texas, United States, 75390 | |
| The University of Texas Health Science Center at Houston | |
| Houston, Texas, United States, 77030 | |
| United States, Utah | |
| Intermountain Medical Center | |
| Murray, Utah, United States, 84157-7000 | |
| United States, Virginia | |
| Inova Transplant Center | |
| Falls Church, Virginia, United States, 22042 | |
| Belgium | |
| University Hospital Gasthuisberg | |
| Leuven, Belgium, 3000 | |
| Canada, Alberta | |
| University of Calgary | |
| Calgary, Alberta, Canada, T1Y 6J4 | |
| University of Alberta Hospitals | |
| Edmonton, Alberta, Canada, T6G 2B7 | |
| Canada, British Columbia | |
| Vancouver Coastal Health Respiratory Clinic | |
| Vancouver, British Columbia, Canada, V5Z 1M9 | |
| Canada, Ontario | |
| London Health Sciences Center | |
| London, Ontario, Canada, N6A 4G5 | |
| Toronto General Hospital | |
| Toronto, Ontario, Canada, M5G 2N2 | |
| France | |
| Hospital Claude Huriez | |
| Lille, Cedex, France, 59037 | |
| Hospital Haut Leveque | |
| Pessac, Cedex, France, 33604 | |
| Hospital Cavale Blanche | |
| Brest, France, 29609 | |
| Germany | |
| Universitaetsklinikum Dresden | |
| Dresden, Germany, 01307 | |
| University Hospital Greifswald | |
| Greifswald, Germany, 17475 | |
| Universitaetsklinikum Heidelberg | |
| Heidelberg, Germany, 69120 | |
| Israel | |
| Pulmonology Department Rambam Medical Center | |
| Haifa, Israel, 31096 | |
| Lady Davis Carmel Medical Centre | |
| Haifa, Israel, 34362 | |
| Pulmonary institute | |
| Ramat Gan, Israel, 52621 | |
| Italy | |
| Azienda Ospedaliera Universitaria | |
| Naples, Italy | |
| Netherlands | |
| VUMC | |
| Amsterdam, Netherlands, 1007 | |
| Portugal | |
| Hospital de Santa Marta | |
| Lisboa, Portugal, 1160-024 | |
| Spain | |
| Hospital Clinic I Provincial de Barcelona | |
| Barcelona, Spain, 08036 | |
| Hospital 12 de Octubre | |
| Madrid, Spain, 28041 | |
| Sweden | |
| Lund University Hospital | |
| Lund, Sweden, 221 85 | |
| United Kingdom | |
| Royal Free Hospital NHS Trust | |
| London, United Kingdom, NW3 2QG | |
Sponsors and Collaborators
United Therapeutics
Investigators
| Study Chair: | Lewis Rubin, MD | University of California, San Diego |
More Information
No publications provided
| Responsible Party: | United Therapeutics |
| ClinicalTrials.gov Identifier: | NCT00887978 History of Changes |
| Other Study ID Numbers: | TDE-PH-308 |
| Study First Received: | April 23, 2009 |
| Results First Received: | November 2, 2012 |
| Last Updated: | December 7, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Hypertension, Pulmonary Hypertension Lung Diseases Respiratory Tract Diseases Vascular Diseases Cardiovascular Diseases |
Treprostinil Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 18, 2013