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

Pulmonary Arterial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01477333
• Other study ID #: TDE-PH-203
• Status: Completed
• Phase: Phase 2
• Start date: October 2011
• Est. completion date: November 2013

Study information

• Verified date: January 2017
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• UT-15C SR
Initiated at 0.125 mg BID, titrated as clinically indicated.
• Tyvaso Inhalation Solution
Administered as at least 9 breaths 4 times daily for at least 4 weeks prior to Baseline

Locations

Country	Name	City	State
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Hemodynamic Parameters From Baseline to 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).	Baseline and Week 24
Primary	Change in Hemodynamic Parameter (Heart Rate) From Baseline to 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.	Baseline and Week 24
Primary	Change in Hemodynamic Parameters (Arterial and Venous Oxygen Saturation) From Baseline to 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).	Baseline and Week 24
Primary	Change in Hemodynamic Parameter (Cardiac Output) From Baseline to 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.	Baseline and Week 24
Primary	Change in Hemodynamic Parameter (Cardiac Index) From Baseline to 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).	Baseline and Week 24
Primary	Change in Hemodynamic Parameter (Pulmonary Vascular Resistance Index) From Baseline to 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).	Baseline and Week 24
Secondary	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.	Baseline and Weeks 4, 12, and 24
Secondary	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 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.	Clinical worsening was assessed continuously from Baseline through each subject's last study visit
Secondary	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).	Baseline and Weeks 4, 8, 12, and 24
Secondary	N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Over the 24-week Treatment Period.	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.	Baseline and Weeks 12 and 24