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

Phase 3

Withdrawn

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Oral Treprostinil; Drug: Placebo

• Registration Number: NCT02999906
• Lead Sponsor: United Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-19
• Study First Submitted QC: 2016-12-19
• Study First Posted: 2016-12-21
• Status Verified: 2017-10
• Study Start: 2017-10
• Last Update Submitted: 2017-10-31
• Last Update Posted: 2017-11-01
• Primary Completion: 2021-12
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active	Oral Treprostinil	Oral treprostinil sustained release tablet
Placebo	Placebo	Matching placebo (sugar pill)

Primary Outcome Measures

Name	Time	Method
Change in 6-Minute Walk Distance (6MWD)	Baseline to Week 28

Secondary Outcome Measures

Name	Time	Method
Compare the effects of triple therapy versus dual therapy on the time to clinical worsening	Baseline to Week 28	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
Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations From Baseline to Week 28	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.
Number of Participants with a Change From Baseline World Health Organization (WHO) Functional Classification at Week 28.	Baseline to 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.
Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 28.	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.