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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00423592
First received: January 17, 2007
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Hypertension
Drug: ambrisentan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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).

  • A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).

  • 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 ] [ Designated as safety issue: No ]
    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).


Enrollment: 36
Study Start Date: May 2005
Study Completion Date: March 2009
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ambrisentan
    All eligible subjects received 2.5 mg ambrisentan once daily for a period of 4 weeks before increasing the dose to 5 mg once daily. After Week 24, investigators were allowed to adjust the dose of ambrisentan as clinically indicated (available doses were 2.5, 5, and 10 mg).
  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00423592     History of Changes
Other Study ID Numbers: AMB-222
Study First Received: January 17, 2007
Results First Received: May 14, 2010
Last Updated: June 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014