Clinical trial NCT01477333: Addition of UT-15C SR to Pulmonary Arterial Hypertension Patients Currently Receiving Tyvaso®
Official title: An Evaluation of the Safety and Efficacy of the Addition of UT-15C SR to Pulmonary Arterial Hypertension Patients Currently Receiving Tyvaso®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Tyvaso
UT-15C SR
PAH
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-11-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Significant inclusion criteria included:

1. Subjects were between 18 to 75 years of age
2. 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)
3. Had been receiving Tyvaso for at least 4 weeks (≥9 breaths, 4 times a day \[QID\]) and required additional therapy
4. 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)

Significant exclusion criteria included:

1. The subject was pregnant or lactating
2. The subject had previously received UT-15C SR
3. The subject had added, discontinued or changed the dosing regimen (i.e., prescription) of conventional PAH therapies (e.g., oral vasodilators, oxygen, digoxin) within 21 days of Baseline
4. The subject was receiving a FDA approved PAH therapy (e.g., ERA and/or PDE-5 inhibitor) for less than 30 days prior to Baseline, or the dose had been modified within 30 days of Baseline
5. The subject had any disease associated with PAH other than collagen vascular disease, HIV infection, repaired congenital systemic-to-pulmonary shunts (for at least 5 years), or appetite suppressant/toxin use (e.g., portal hypertension, chronic thromboembolic disease, pulmonary veno-occlusive disease, etc.), or had an atrial septostomy
6. The subject had ischemic heart disease prior to Screening, or left ventricular dysfunction as evidenced by a mean PCWP (or a left ventricular end diastolic pressure) greater than 15 mmHg or left ventricular ejection fraction (LVEF) less than 40% as assessed by either multigated angiogram (MUGA), angiography or echocardiography. Patients with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload were not excluded.
7. The subject had uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg at Baseline.

Primary outcomes:
measure: Change in Hemodynamic Parameters From Baseline to Week 24.
timeFrame: Baseline and Week 24
measure: Change in Hemodynamic Parameter (Heart Rate) From Baseline to Week 24.
timeFrame: Baseline and Week 24
measure: Change in Hemodynamic Parameters (Arterial and Venous Oxygen Saturation) From Baseline to Week 24.
timeFrame: Baseline and Week 24
measure: Change in Hemodynamic Parameter (Cardiac Output) From Baseline to Week 24.
timeFrame: Baseline and Week 24
measure: Change in Hemodynamic Parameter (Cardiac Index) From Baseline to Week 24.
timeFrame: Baseline and Week 24
measure: Change in Hemodynamic Parameter (Pulmonary Vascular Resistance Index) From Baseline to Week 24.
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Over the 24-week Treatment Period.
timeFrame: Baseline and Weeks 4, 12, and 24
measure: Time to Clinical Worsening Over the Treatment Period.
timeFrame: Clinical worsening was assessed continuously from Baseline through each subject's last study visit
measure: Shift From Baseline in World Health Organization (WHO) Functional Class Over the 24-week Treatment Period.
timeFrame: Baseline and Weeks 4, 8, 12, and 24
measure: N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Over the 24-week Treatment Period.
timeFrame: Baseline and Weeks 12 and 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: Associate Director, Medical Development
name: Cynthia Madden, MD, MPH
role: STUDY_CHAIR
References: