Phase 2 Study of Ambrisentan for Liver Function Test Rescue in Pulmonary Arterial Hypertension

June 7, 2013 updated by: Gilead Sciences

A Phase 2, Open-label, Multicenter Study Evaluating Ambrisentan in Subjects With Pulmonary Arterial Hypertension Who Have Previously Discontinued Endothelin Receptor Antagonist Therapy Due to Serum Aminotransferase Abnormalities

This Phase 2 study was to determine the incidence of increased serum aminotransferase concentrations (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]), as well as the overall safety and tolerability of ambrisentan, in participants with pulmonary arterial hypertension (PAH), idiopathic PAH (IPAH), or familial PAH (FPAH) who had previously discontinued ERA therapy (bosentan or sitaxsentan) due to increased serum ALT or AST concentrations.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Summary of Inclusion Criteria:

  • Males and Females between 12 and 75 years of age
  • Current diagnosis of IPAH, FPAH, or PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts, anorexigen use, HIV infection
  • Must have previously discontinued bosentan or sitaxsentan therapy due to serum aminotransferase (ALT and/or AST) concentrations > 3 x ULN
  • Must have normal (< 1 x ULN) serum ALT and AST concentrations at screening
  • Six-minute Walk distance of at least 150 meters at screening
  • If receiving sildenafil or a clinically approved prostanoid for PAH, must have been on stable therapy for at least 4 weeks prior to screening
  • Subjects with a diagnosis of HIV must have stable disease status during the screening period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Incidence of Confirmed Serum Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Concentrations > 3 x the Upper Limit of Normal (ULN) Considered to be Related to Ambrisentan and Resulted in Discontinuation of Study Drug.
Time Frame: Week 12
The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations > 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of study drug. Safety analysis set included all participants who received at least 1 dose of study drug.
Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Incidence of Confirmed Serum ALT or AST Concentrations > 5 x ULN That Were Related to Ambrisentan and Resulted in Discontinuation of Study Drug.
Time Frame: Week 12
The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations > 5 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in discontinuation of drug. Safety analysis set included all participants who received at least 1 dose of study drug.
Week 12
The Incidence of Confirmed Serum ALT or AST Concentrations > 3 x ULN That Were Related to Ambrisentan and Resulted in Dose Reduction
Time Frame: Week 12
The number of participants in the safety analysis set with confirmed serum ALT or AST concentrations > 3 x ULN during 12 weeks of ambrisentan therapy that were related to ambrisentan and resulted in dose reduction. Safety analysis set included all participants who received at least 1 dose of study drug.
Week 12
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in the 6-Minute Walk Distance Test (6MWD)
Time Frame: Baseline to Week 12
The 6MWD test is a measure of exercise tolerance, and measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.
Baseline to Week 12
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise
Time Frame: Baseline to Week 12
Change from baseline evaluated after 12 weeks of ambrisentan therapy in Borg dyspnea index (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Baseline to Week 12
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class
Time Frame: Baseline to Week 12
Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes undue dyspnea or fatigue, chest pain, or near syncope. II) PH; ordinary physical activity slightly limited and causes undue dyspnea or fatigue, chest pain, or near syncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope; comfortable at rest. IV) PH; physical activity causes symptoms and increased discomfort; signs of right heart failure; dyspnea/fatigue possibly at rest.
Baseline to Week 12
A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Short Form 36 (SF-36) Health Survey Scale - Composite Physical Health
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The first 6 concepts constitute the physical component summary. Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Composite Mental Health
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). The last 5 concepts constitute the mental component summary. Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Physical Functioning
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Physical
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Bodily Pain
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - General Health
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Vitality
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Social Functioning
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Emotional
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12
Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Mental Health
Time Frame: Baseline to Week 12
The SF-36 Health Survey is a self-reporting, multi-item scale measuring 8 health concepts: 1) physical functioning, 2) role limitations due to physical health problems, 3) bodily pain, 4) general health, 5) vitality (energy/fatigue), 6) social functioning, 7) role limitations due to emotional problems and 8) mental health (psychological distress and psychological well-being). Each item is scored from 0 to 100 (least healthy to most healthy).
Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2005

Primary Completion (Actual)

January 1, 2006

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

January 17, 2007

First Submitted That Met QC Criteria

January 17, 2007

First Posted (Estimate)

January 18, 2007

Study Record Updates

Last Update Posted (Estimate)

June 17, 2013

Last Update Submitted That Met QC Criteria

June 7, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMB-222

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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