FREEDOM DR: Oral Treprostinil in Combination With an Endothelin Receptor Antagonist (ERA) and/or a Phosphodiesterase-5 (PDE-5) Inhibitor or as Monotherapy for the Treatment of Pulmonary Arterial Hypertension (PAH)

Study Overview
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Brief Summary
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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)or as a monotherapy treatment. Study visits will occur at 4 week intervals for 12 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. At the end of the first 12-weeks, the patient will be un-blinded. Patients will continue with another 12-Week open label portion with visits occuring at 4-week intervals. Patients who complete all assessments for 24-weeks will also be eligible to enter a 36 month open-label, extension phase study (FREEDOM - EXT).

Detailed Description
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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)or as a monotherapy treatment. Study visits will occur at 4 week intervals for 12 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. At the end of the first 12-weeks, the patient will be un-blinded. Patients will continue with another 12-Week open label portion with visits occuring at 4-week intervals. Patients who complete all assessments for 24-weeks will also be eligible to enter a 36 month open-label, extension phase study (FREEDOM - EXT).

Official Title
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FREEDOM DR: An International, Multi-Center, 12-Week, Double Blind, Randomized, Placebo-Controlled, Parallel Group Study Followed by a 12-Week Open-Label Extension Study to Assess the Efficacy, Safety, and Dose Response of UT-15C SR in Subjects With Pulmonary Hypertension

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: UT-15C 1 mg
* Drug: UT-15C 0.25 mg
* Drug: UT-15C 5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 and 70 years of age, inclusive Body weight at least 50 kilograms PAH that is either idiopathic/familial; associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); associated with collagen vascular disease; 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 or not currently receiving approved PAH therapy. Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH. Reliable and cooperative with protocol requirements. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: UT-15C 0.25 mg<br>UT-15C 0.25 mg | Drug: UT-15C 0.25 mg<br>* UT-15C 0.25 mg<br>|
| Active Comparator: UT-15C 1 mg<br>UT-15C 1 mg | Drug: UT-15C 1 mg<br>* UT-15C 1 mg<br>|
| Active Comparator: UT-15C 5 mg<br>UT-15C 5 mg | Drug: UT-15C 5 mg<br>* UT-15C 5 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in six-minute walk distance from Baseline to Week 12 |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Borg Dyspnea Score |  | 12 weeks | 
| Clinical Worsening Assessment |  | 12 weeks | 
| Dyspnea Fatigue Index |  | 12 weeks | 
| Symptoms of PAH |  | 12 weeks | 
| World Health Organization (WHO) Functional Class |  | 12 weeks | 
| Trough 6-Minute Walk Distance |  | 12 weeks | 
| Trough Borg Dyspnea Score |  | 12 weeks | 
| Pro-B-type natriuretic peptide (Pro-BNP) |  | 12 weeks | 
| Optional hemodynamic parameters |  | 12 weeks | 
| Adverse events |  | 12 weeks | 
| Clinical Laboratory parameters |  | 12 weeks | 
| Electrocardiogram findings |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Arterial Hypertension