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Completed

NCT Number: NCT00380068

Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension

The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in a broad population of participants with pulmonary hypertension (PH). Secondary objectives of this study were to evaluate the effects of ambrisentan on other clinical measures of pulmonary arterial hypertension (PAH), long-term treatment success, and survival.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

St. Vincent's Hospital, Darlinghurst, New South Wales, Australia

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About this study

This study was to enroll up to 200 participants with PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5). Participants with left heart disease or left heart failure were excluded (WHO Group 2). Participants could be receiving prostacyclin or sildenafil therapy at baseline, and participants who previously discontinued either bosentan, sitaxsentan, or both, due to liver function test abnormalities were eligible.

Who can participate

Healthy volunteers accepted: No

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

Summarized Inclusion Criteria:

  • 18 years of age or older
  • Current diagnosis of PH associated with an acceptable etiology as outlined in the protocol, including: PH due to the following etiologies: 1) PAH including idiopathic and familial PAH and PAH associated with collagen vascular disease, congenital systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1); 2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing, and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO Group 5).
  • Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium channel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy
  • Right heart catheterization completed prior to screening must meet pre-specified criteria
  • Female participants of childbearing potential must have a negative serum pregnancy test and must agree to use a reliable double method of contraception until study completion and for at least four weeks following their final study visit.
  • Male participants must be informed of the potential risks of testicular tubular atrophy and infertility associated with taking ambrisentan and queried regarding his understanding of the potential risks as described in the Informed Consent Form.

Summarized Exclusion Criteria:

  • Participation in a previous clinical study with ambrisentan
  • Bosentan or sitaxsentan use within four weeks prior to the screening visit
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is greater than 3 times the upper limit of normal at the screening visit
  • Pulmonary function tests not meeting the following pre-specified criteria: 1) mean pulmonary arterial pressure (PAP) >= 25 mm Hg; 2) PVR > 3 mm Hg/L/min; 3) pulmonary capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) < 15 mm Hg; 4) total lung capacity (TLC) >= 70% of predicted normal for participants without ILD or >= 60% of predicted normal in participants with ILD; forced expiratory volume in 1 second (FEV1) >= 65% of predicted normal in participants without COPD or >= 50% of predicted normal in participants with COPD
  • Contraindication to treatment with endothelin receptor antagonist (ERA)
  • History of malignancies other than basal cell carcinoma of the skin or in situ carcinoma of the cervix within the past five years
  • Female participant who is pregnant or breastfeeding

Treatment and study plan

Ambrisentan

Drug

Oral tablets taken once daily.

Other names: Letairis, Volibris

Primary outcomes

  1. Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)

    Time frame: Baseline to Week 24

Secondary outcomes

  1. Change From Baseline to Week 24 in Borg Dyspnea Index

    Time frame: Baseline to Week 24

    Change from Baseline to Week 24 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.

  2. Change From Baseline to Week 48 in Borg Dyspnea Index

    Time frame: Baseline to Week 48

    Change from Baseline to Week 48 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.

  3. Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)

    Time frame: Baseline to Week 24

  4. Percent Change From Baseline to Week 48 in BNP

    Time frame: Baseline to Week 48

  5. Change From Baseline to Week 24 in WHO Functional Class

    Time frame: Baseline to Week 24

    Change from baseline in World Health Organization functional class (WHO) at Week 24 is the incidence of participants that improved, had no change, or worsened. WHO categories are 1 to 4 with the worse category at 4. Improvement = a category change from baseline of <= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.

  6. Change From Baseline to Week 48 in WHO Functional Class

    Time frame: Baseline to Week 48

    Change from baseline in WHO at Week 48 is expressed as the incidence of participants that improved, had no change or worsened. WHO categories range from 1 to 4 with the worse category at 4. Improvement = a category change from baseline of <= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.

  7. Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale

    Time frame: Baseline to Week 24

    Change from baseline to Week 24 in the SF-36 health survey physical functioning scale. 10 activities rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General United States (US) population mean and standard deviation (SD). Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.

  8. Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale

    Time frame: Baseline to Week 48

    Change from baseline to Week 48 in the SF-36 health survey physical functioning scale. 10 activities are rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General US population mean and standard deviation. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and standard deviation of 10.

  9. Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24

    Time frame: Baseline to Week 24

    Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents

  10. Percent of Participants With no Clinical Worsening of PH at Week 48

    Time frame: Baseline to Week 48

    Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents

  11. Failure-free Treatment Status

    Time frame: Baseline to Week 24

    Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents

  12. Failure-free Treatment Status

    Time frame: Baseline to Week 48

    Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents

  13. Monotherapy Treatment Status

    Time frame: Baseline to Week 24

    Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment

  14. Monotherapy Treatment Status

    Time frame: Baseline to Week 48

    Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment

  15. Long-term Survival

    Time frame: Baseline to Week 24

    Defined as not dying during study participation

  16. Long-term Survival

    Time frame: Baseline to Week 48

    Defined as not dying during study participation

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study title

ARIES-3: A Phase 3, Long-Term, Open-Label, Multicenter Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension

Important dates

Study start
2006
Primary completion
2008
Study completion
2009
First posted
Sep 25, 2006
Registry last updated
Apr 5, 2012

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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