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®

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01477333

Enrollment

Registered

2011-11-22

Start date

2011-10-31

Completion date

2013-11-30

Last updated

2023-12-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Arterial Hypertension

Keywords

Tyvaso, UT-15C SR, PAH

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.

Interventions

DRUGUT-15C SR

Initiated at 0.125 mg BID, titrated as clinically indicated.

DRUGTyvaso Inhalation Solution

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion 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.

Design outcomes

Primary

Measure	Time frame	Description
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).
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 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).

Secondary

Measure	Time frame	Description
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.
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.

Countries

United States

Participant flow

Recruitment details

The recruitment period for this study was October 2011 to November 2013.

Participants by arm

Arm	Count
UT-15C SR BID UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.	18
Total	18

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Clinical Deterioration	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	UT-15C SR BID
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	4 Participants
Age, Categorical Between 18 and 65 years	14 Participants
Age, Continuous	51.3 years
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	18 Participants
Region of Enrollment United States	18 participants
Sex: Female, Male Female	13 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	18 / 18
serious Total, serious adverse events	2 / 18