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)

• Borg Dyspnea Score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Clinical Worsening Assessment [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Dyspnea Fatigue Index [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Symptoms of PAH [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• World Health Organization (WHO) Functional Class [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Trough 6-Minute Walk Distance [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Trough Borg Dyspnea Score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Pro-B-type natriuretic peptide (Pro-BNP) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Optional hemodynamic parameters [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Clinical Laboratory parameters [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
• Electrocardiogram findings [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

• Borg Dyspnea Score
• Clinical Worsening Assessment
• Dyspnea Fatigue Index
• Symptoms of PAH
• World Health Organization (WHO) Functional Class
• Trough 6-Minute Walk Distance
• Trough Borg Dyspnea Score
• Pro-B-type natriuetic peptide (Pro-BNP)
• Optional hemodynamic parameters
• Adverse events
• Clinical Laboratory parameters
• Electrocardiogram findings

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).

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).

• Drug: UT-15C 1 mg
  UT-15C 1 mg
• Drug: UT-15C 0.25 mg
  UT-15C 0.25 mg
• Drug: UT-15C 5 mg
  UT-15C 5 mg
• Drug: Placebo
  Placebo

• Placebo Comparator: Placebo
  placebo
  Intervention: Drug: Placebo
• Active Comparator: UT-15C 0.25 mg
  UT-15C 0.25 mg
  Intervention: Drug: UT-15C 0.25 mg
• Active Comparator: UT-15C 1 mg
  UT-15C 1 mg
  Intervention: Drug: UT-15C 1 mg
• Active Comparator: UT-15C 5 mg
  UT-15C 5 mg
  Intervention: Drug: UT-15C 5 mg

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