Addition of UT-15C SR to Pulmonary Arterial Hypertension Patients Currently Receiving Tyvaso®

An Evaluation of the Safety and Efficacy of the Addition of UT-15C SR to Pulmonary Arterial Hypertension Patients Currently Receiving Tyvaso®

The purpose of this multi-center, open-label, safety and tolerability study was to assess the addition of oral treprostinil (UT-15C sustained release [SR] tablets) to subjects currently receiving Tyvaso (treprostinil) inhalation solution. During the 24-week evaluation period, the study evaluated the changes in the following assessments: hemodynamics, 6-minute walk test (6MWT), Borg dyspnea score, N-Terminal pro-brain natriuretic peptide (NT-proBNP), World Health Organization (WHO) Functional Class, and safety assessments. Eligible subjects had a diagnosis of pulmonary arterial hypertension (PAH), currently were receiving Tyvaso, and may have been receiving other approved PAH specific oral therapies (endothelin receptor antagonists [ERAs] and/or phosphodiesterase type 5 inhibitor [PDE5-I], if at a stable dose for ≥30 days). At Baseline, subjects received the first dose of 0.125 mg UT-15C SR.

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included the following: mean pulmonary arterial pressure (PAPm), mean systemic arterial pressure (SAPm), mean right atrial pressure (RAPm), and mean pulmonary capillary wedge pressure (PCWPm).

Heart rate was assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SvO2).

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included cardiac index (CI).

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit. Cardiopulmonary hemodynamic measurements included the following: pulmonary vascular resistance index (PVRI).

Change in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Over the 24-week Treatment Period.

The 6MWT was conducted at Baseline, 2 to 4 hours after the last Tyvaso dose, and prior to first dose of UT-15C SR. The 6MWT was also performed at Weeks 4, 12, and 24, or at the time of premature termination of study drug if prior to the Week 24 visit.

Clinical worsening was assessed continuously from Baseline through each subject's last study visit. Clinical worsening was defined as the occurrence of any one or more of the following: death (all causes), hospitalization as a result of worsening pulmonary arterial hypertension (PAH), and initiation of a parenteral prostacyclin.

Shift From Baseline in World Health Organization (WHO) Functional Class Over the 24-week Treatment Period.

The WHO functional classification for pulmonary hypertension was assessed at Baseline prior to starting UT-15C SR, Weeks 4, 8, 12, and 24, or at the time of premature termination if prior to Week 24. The WHO functional classification ranges from I (patient's disease does not affect daily activities) to IV (patient's disease causes severe impairment).

NT-proBNP was assessed at Baseline prior to starting UT-15C SR, Weeks 12 and 24, or at the time of premature termination if prior to Week 24. Blood for NT-proBNP assessment was collected before the 6MWT was conducted.

Significant inclusion criteria includes: Subjects were between 18 to 75 years of age Diagnosis of PAH: Idiopathic; Heritable; Associated with: Collagen vascular disease, Human immunodeficiency virus (HIV) infection, appetite suppressant or toxin use, or repaired congenital systemic-to-pulmonary shunts (repaired ≥5 years) Had been receiving Tyvaso for at least 4 weeks (≥9 breaths, 4 times a day [QID]) and required additional therapy In addition to Tyvaso, subjects may have been receiving other approved PAH specific oral therapies (ERAs and/or PDE-5 inhibitors, if at a stable dose).