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Completed

NCT Number: NCT00423592

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

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.

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Key information

Conditions

Pulmonary Hypertension Cardiovascular Diseases Hypertension Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases Vascular Diseases

Age range

12 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ambrisentan

Drug

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).

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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).

  7. 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).

  8. 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).

  9. 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).

  10. 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).

  11. 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).

  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).

  13. 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).

  14. 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).

  15. 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).

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2006
Study completion
2009
First posted
Jan 18, 2007
Registry last updated
Jun 17, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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