Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension (FREEDOM-C2)
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).
|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|
- 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).
- 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)
- 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.
|Study Start Date:||June 2009|
|Study Completion Date:||July 2011|
|Primary Completion Date:||July 2011 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Identical placebo tablets to UT-15C, doses were titrated in the same manner
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
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|Study Chair:||Lewis Rubin, MD||University of California, San Diego|