Phase 3
N=224
Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
Pulmonary Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT00380068 ↗Enrolled (actual)
224
Serious AEs
43.3%
Results posted
Nov 2010
Primary outcome: Primary: Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD) — 20.5 meters — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Ambrisentan (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Jul 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD) |
20.5 | <0.001 sig |
| SECONDARY Change From Baseline to Week 24 in Borg Dyspnea Index |
-0.5 | <0.001 sig |
| SECONDARY Change From Baseline to Week 48 in Borg Dyspnea Index |
-0.6 | 0.001 sig |
| SECONDARY Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP) |
-25.5 | — |
| SECONDARY Percent Change From Baseline to Week 48 in BNP |
-29.2 | — |
| SECONDARY Change From Baseline to Week 24 in WHO Functional Class |
0; 0.9; 22.2; 70.1; 6.8; 0 | <0.001 sig |
| SECONDARY Change From Baseline to Week 48 in WHO Functional Class |
0; 1.7; 34.5; 57.1; 6.7; 0 | <0.001 sig |
| SECONDARY Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale |
2.88 | <0.001 sig |
| SECONDARY Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale |
2.80 | <0.001 sig |
| SECONDARY Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24 |
89.4 | — |
| SECONDARY Percent of Participants With no Clinical Worsening of PH at Week 48 |
84.1 | — |
| SECONDARY Failure-free Treatment Status |
92.9 | — |
| SECONDARY Failure-free Treatment Status |
92.9 | — |
| SECONDARY Monotherapy Treatment Status |
90.0 | — |
| SECONDARY Monotherapy Treatment Status |
90.0 | — |
| SECONDARY Long-term Survival |
95.3 | — |
| SECONDARY Long-term Survival |
95.3 | — |
Summary
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.
Eligibility Criteria
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) = 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
Data sourced from ClinicalTrials.gov (NCT00380068). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.