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

Phase 2
Completed
Conditions
Pulmonary Arterial Hypertension
Interventions
Registration Number
NCT01477333
Lead Sponsor
United Therapeutics
Brief Summary

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.

Detailed Description

This was a multi-center, open-label, safety and tolerability study in WHO Group 1 PAH subjects adding UT-15C SR to Tyvaso and PAH approved background therapy. This study had a 24-week evaluation period followed by a long term safety period. Six study visits occurred in the first 24 weeks of study; Screening, Baseline, Week 4, Week 8, Week 12, and Week 24 visits. Right heart catheterization occurred between 2-4 hours following the last Tyvaso dose at Baseline (prior to the administration of UT-15C SR) and Week 24.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
18
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
UT-15C SR BIDUT-15C SRInitiated at 0.125 mg twice daily (BID), titrated as clinically indicated.
UT-15C SR BIDTyvaso Inhalation SolutionInitiated at 0.125 mg twice daily (BID), titrated as clinically indicated.
Primary Outcome Measures
NameTimeMethod
Change in Hemodynamic Parameters From Baseline to Week 24.Baseline and Week 24

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).

Change in Hemodynamic Parameter (Heart Rate) From Baseline to Week 24.Baseline and Week 24

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.

Change in Hemodynamic Parameters (Arterial and Venous Oxygen Saturation) From Baseline to Week 24.Baseline and Week 24

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).

Change in Hemodynamic Parameter (Cardiac Output) From Baseline to Week 24.Baseline and Week 24

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.

Change in Hemodynamic Parameter (Cardiac Index) From Baseline to Week 24.Baseline and Week 24

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).

Change in Hemodynamic Parameter (Pulmonary Vascular Resistance Index) From Baseline to Week 24.Baseline and Week 24

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).

Secondary Outcome Measures
NameTimeMethod
Shift From Baseline in World Health Organization (WHO) Functional Class Over the 24-week Treatment Period.Baseline and Weeks 4, 8, 12, and 24

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).

N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Over the 24-week Treatment Period.Baseline and Weeks 12 and 24

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.

Change in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Over the 24-week Treatment Period.Baseline and Weeks 4, 12, and 24

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.

Time to Clinical Worsening Over the Treatment Period.Clinical worsening was assessed continuously from Baseline through each subject's last study 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.

Trial Locations

Locations (6)

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

UT Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

The University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

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