Study to Compare Triple Therapy (Oral Treprostinil, Ambrisentan, and Tadalafil) With Dual Therapy (Ambrisentan, Tadalafil, and Placebo) in Subjects With Pulmonary Arterial Hypertension

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Study to Compare the Efficacy and Safety of Triple Therapy (Oral Treprostinil, Ambrisentan, and Tadalafil) With Dual Therapy (Ambrisentan, Tadalafil, and Placebo) in Subjects With Pulmonary Arterial Hypertension

This is a multicenter, randomized (2:1 oral treprostinil: placebo), double-blind, placebo-controlled study in subjects with Pulmonary Arterial Hypertension (PAH) who are currently receiving background dual therapy (ambrisentan, tadalafil) for at least 30 days at randomization for their PAH. Once randomized, subjects will return for 5 study visits up to Week 28 during the blinded period. After the Week 28 Visit, eligible subjects will transition to the open-label period of the study for up to 20 weeks.

Study Overview

• Status: Withdrawn
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Oral Treprostinil

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Between 18 and 79 years of age, inclusive
2. PAH that is idiopathic / heritable, PAH associated with connective tissue disease, HIV infection, repaired congenital systemic-to-pulmonary shunts (repaired > 1 year), or appetite suppressant / toxin use
3. Receiving dual therapy (ambrisentan and tadalafil)
4. Previous testing (e.g. right heart catheterization, echocardiography) consistent with diagnosis of PAH

Exclusion Criteria:

1. Nursing or pregnant
2. PAH due to conditions other than noted in the above inclusion criteria
3. Received PAH-specific drug therapy for >2 years
4. History of uncontrolled sleep apnea, severe liver disease, severe renal impairment, left sided heart disease, uncontrolled systemic hypertension
5. Participated in an investigational drug or device study within 90 days prior to signing consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo (sugar pill)	Drug: Placebo; Placebo (sugar pill) for three times daily oral administration; Other Names: matching placebo (sugar pill)
Active Comparator: Active; Oral treprostinil sustained release tablet	Drug: Oral Treprostinil; Sustained release oral tablets for three times daily administration; Other Names: treprostinil diethanolamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in 6-Minute Walk Distance (6MWD)	Baseline to Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the effects of triple therapy versus dual therapy on the time to clinical worsening	clinical worsening is defined by 1 of the following: Death (all causes); Hospitalization due to worsening PAH; Initiation of long-term parenteral therapy; Disease progression; Unsatisfactory long-term clinical response	Baseline to Week 28
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations From Baseline to Week 28	The level of this biomarker of the (NT-proBNP) serum concentration will be assessed to compare the severity of heart failure at Baseline and Week 28.	Baseline to week 28
Number of Participants with a Change From Baseline World Health Organization (WHO) Functional Classification at Week 28.	The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.	Baseline to week 28
Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 28.	The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 025; high scores indicate more symptoms), Activity (Score 030; low score indicates good functioning) and Quality of Life (025; high scores indicate poor QoL). The sum of these scores equates to the Total score (080). In the CAMPHOR scores, lower scores indicate improvements.	Baseline to week 28

Collaborators and Investigators

• Sponsor: United Therapeutics

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2017
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimate): December 21, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: dual therapy; PAH; Oral Treprostinil; 6 Minute Walk Test
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: TDE-PH-313

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No