A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension
- Registration Number
- NCT01104870
- Lead Sponsor
- United Therapeutics
- Brief Summary
This is a prospective, randomized, parallel group study to assess the hemodynamic effect of three different dose regimens of a sustained release (SR) tablet of UT-15C in patients with exercise-induced pulmonary hypertension (PH), as measured by the change in peak total pulmonary resistance index (TPRI) during exercise from Baseline to Week 12.
- Detailed Description
Prospective, randomized, parallel group study with two periods: a 10 week, dose titration period, followed by a 2 week, dose maintenance period in patients with exercise-induced PH.
The study population will be randomized into Dose Group 1, Dose Group 2, or an Individual Maximum Tolerated Dose (iMTD) of UT-15C SR by Week 10 and maintained through Week 12. Patients may be either currently receiving an approved oral background therapy for their PH (phosphodiesterase-5 \[PDE-5\] inhibitor, OR endothelin receptor antagonist \[ERA\]) (no dual background therapy), or not currently receiving therapy for PH.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Group 1 UT-15C UT-15C 0.25 mg twice daily Dose Group 2 UT-15C UT-15C 1.25 mg twice daily Dose Group 3 UT-15C UT-15C individual Maximum Tolerated Dose
- Primary Outcome Measures
Name Time Method Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12 Baseline and Week 12 The effects of 12-week treatment with different doses of UT-15C on peak TPRI during exercise will be evaluated by comparing the change from Baseline to Week 12 at peak wattage on a pairwise basis between treatment groups.
The primary measure of efficacy was the change from Baseline to Week 12 in peak TPRI during exercise assessed 3 to 6 hours after the subject's morning dose of UT-15C to obtain measurements at peak concentrations of treprostinil. The equation used to determine the Total Pulmonary Resistance Index (TPRI) (mmHg/\[L/min/m\^2\]) is Mean Pulmonary Artery Pressure (PAPm)/ Cardiac Index (CI).
- Secondary Outcome Measures
Name Time Method Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12 Baseline and Week 12 Pulmonary hypertension (PH) is an increase in pressure in the pulmonary vasculature defined as a mean pulmonary artery pressure (PAPm) greater than 25 mmHg at rest or greater than 30 mmHg with exercise, as measured by right heart catheterization. The PAPm values and their respective changes from Baseline to Week 12 at peak exercise will be summarized by treatment group and measured by Swan-Ganz right heart catheterization.
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12 Baseline and Week 12 The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) 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).
Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12 Baseline and Week 12 The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline to Week 12, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS). Subjects were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes. Distance \<500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance \>800 meters (with no rests) suggests mild or no limitation.
Change in Cardiac Index (CI) From Baseline to Week 12 Baseline and Week 12 Cardiac Index (CI) relates the cardiac output (CO) from left ventricle to body surface area (BSA), thus relating heart performance to the size of the individual. The CI values and their respective changes from Baseline to Week 12 at peak exercise will be summarized by treatment group and measured by Swan-Ganz right heart catheterization.
Change in PH Symptoms From Baseline to Week 12 Change from Baseline at 12 Weeks Symptoms of PH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea were assessed and severity grade values (i.e., 0, 1, 2 or 3) for each symptom were assigned for subjects. A severity of 0 indicated no symptoms, the maximum severity was 3, indicating severe symptoms. Median change in symptom severity from Baseline to Week 12 is described.
Number of Participants With a Change From Baseline World Health Organization (WHO) Functional Classification at Week 12 Change from Baseline at Week 12 The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: 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. Only participants who experienced a change in WHO functional classification from Baseline to Week 12 are described by class change below; all other participants maintained their Baseline WHO functional classification at Week 12.
Change in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations From Baseline to Week 12 Baseline and Week 12 The N-terminal pro-BNP (NT-proBNP) serum concentration was assessed to compare the severity of heart failure at Baseline and Week 12.
Trial Locations
- Locations (9)
The Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
The Carl and Edyth Lindner Research Center at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
University of California Los Angeles Pulmonary Division
🇺🇸Los Angeles, California, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
University of Rochester Medical Center, Mary Parkes Center
🇺🇸Rochester, New York, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Arizona
🇺🇸Tucson, Arizona, United States