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

NCT01477333 | Completed Phase 2 Results

• 1 other identifier: TDE-PH-203
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Tyvaso; UT-15C SR; PAH

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (4)

• 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

• Time to Clinical Worsening Over the Treatment Period.

  Clinical worsening was assessed continuously from Baseline through each subject's last study visit

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

  Baseline and Weeks 4, 8, 12, and 24

• N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Over the 24-week Treatment Period.

  Baseline and Weeks 12 and 24

Study Arms (1)

UT-15C SR BID

EXPERIMENTAL

Initiated at 0.125 mg twice daily (BID), titrated as clinically indicated.

Drug: UT-15C SR; Drug: Tyvaso Inhalation Solution

Interventions

UT-15C SR DRUG

Initiated at 0.125 mg BID, titrated as clinically indicated.

Also known as: treprostinil diethanolamine, sustained release

UT-15C SR BID

Tyvaso Inhalation Solution DRUG

Administered as at least 9 breaths 4 times daily for at least 4 weeks prior to Baseline

Also known as: Treprostinil

UT-15C SR BID

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• The subject was pregnant or lactating
• The subject had previously received UT-15C SR
• 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
• 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
• 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
• 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.
• 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.

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (6)

The University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Kevin LaLiberte, PharmD
• Organization: United Therapeutics Corp.

KLaliberte@unither.com

919-425-8176

Study Officials

• Cynthia Madden, MD, MPH

  Associate Director, Medical Development

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 22, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: December 27, 2023
• Results First Posted: March 6, 2017

Record last verified: 2017-01

Locations

US (6)