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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Oral Treprostinil
Placebo
Sponsored by
United Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring PAH, Oral Treprostinil, dual therapy, 6 Minute Walk Test

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Active Comparator

    Arm Label

    Placebo

    Active

    Arm Description

    Matching placebo (sugar pill)

    Oral treprostinil sustained release tablet

    Outcomes

    Primary Outcome Measures

    Change in 6-Minute Walk Distance (6MWD)

    Secondary Outcome Measures

    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
    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.
    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.
    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.

    Full Information

    First Posted
    December 19, 2016
    Last Updated
    October 31, 2017
    Sponsor
    United Therapeutics
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02999906
    Brief Title
    Study to Compare Triple Therapy (Oral Treprostinil, Ambrisentan, and Tadalafil) With Dual Therapy (Ambrisentan, Tadalafil, and Placebo) in Subjects With Pulmonary Arterial Hypertension
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2017
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    For business reasons.
    Study Start Date
    October 2017 (Anticipated)
    Primary Completion Date
    December 2021 (Anticipated)
    Study Completion Date
    June 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    United Therapeutics

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Arterial Hypertension
    Keywords
    PAH, Oral Treprostinil, dual therapy, 6 Minute Walk Test

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Matching placebo (sugar pill)
    Arm Title
    Active
    Arm Type
    Active Comparator
    Arm Description
    Oral treprostinil sustained release tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Oral Treprostinil
    Other Intervention Name(s)
    treprostinil diethanolamine
    Intervention Description
    Sustained release oral tablets for three times daily administration
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Other Intervention Name(s)
    matching placebo (sugar pill)
    Intervention Description
    Placebo (sugar pill) for three times daily oral administration
    Primary Outcome Measure Information:
    Title
    Change in 6-Minute Walk Distance (6MWD)
    Time Frame
    Baseline to Week 28
    Secondary Outcome Measure Information:
    Title
    Compare the effects of triple therapy versus dual therapy on the time to clinical worsening
    Description
    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
    Time Frame
    Baseline to Week 28
    Title
    Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations From Baseline to Week 28
    Description
    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.
    Time Frame
    Baseline to week 28
    Title
    Number of Participants with a Change From Baseline World Health Organization (WHO) Functional Classification at Week 28.
    Description
    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.
    Time Frame
    Baseline to week 28
    Title
    Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 28.
    Description
    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.
    Time Frame
    Baseline to week 28

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    79 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Between 18 and 79 years of age, inclusive 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 Receiving dual therapy (ambrisentan and tadalafil) Previous testing (e.g. right heart catheterization, echocardiography) consistent with diagnosis of PAH Exclusion Criteria: Nursing or pregnant PAH due to conditions other than noted in the above inclusion criteria Received PAH-specific drug therapy for >2 years History of uncontrolled sleep apnea, severe liver disease, severe renal impairment, left sided heart disease, uncontrolled systemic hypertension Participated in an investigational drug or device study within 90 days prior to signing consent.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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