Phase 2
N=36
Phase 2 Study of Ambrisentan for Liver Function Test Rescue in Pulmonary Arterial Hypertension
Pulmonary Hypertension
Bottom Line
View on ClinicalTrials.gov: NCT00423592 ↗Enrolled (actual)
36
Serious AEs
47.2%
Results posted
Jun 2012
Primary outcome: Primary: 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. — 0 Participants — p=0.01
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ambrisentan (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Gilead Sciences
- Primary completion
- Jan 2006
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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. |
— | 0.01 sig |
| SECONDARY The Incidence of Confirmed Serum ALT or AST Concentrations > 5 x ULN That Were Related to Ambrisentan and Resulted in Discontinuation of Study Drug. |
— | — |
| SECONDARY The Incidence of Confirmed Serum ALT or AST Concentrations > 3 x ULN That Were Related to Ambrisentan and Resulted in Dose Reduction |
— | — |
| SECONDARY A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in the 6-Minute Walk Distance Test (6MWD) |
23.4 | 0.009 sig |
| SECONDARY A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Borg Dyspnea Index Immediately Following Exercise |
-0.5 | 0.046 sig |
| SECONDARY A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in WHO Functional Class |
15; 18; 2 | — |
| SECONDARY A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in Short Form 36 (SF-36) Health Survey Scale - Composite Physical Health |
4.6 | 0.001 sig |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Composite Mental Health |
3.4 | 0.059 |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Physical Functioning |
4.4 | 0.002 sig |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Physical |
7.2 | 0.001 sig |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Bodily Pain |
3.1 | 0.017 sig |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - General Health |
3.0 | 0.046 sig |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Vitality |
4.5 | 0.003 sig |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Social Functioning |
3.5 | 0.059 |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Role Emotional |
3.9 | 0.152 |
| SECONDARY Secondary Outcome: A Change From Baseline Evaluated After 12 Weeks of Ambrisentan Therapy in SF-36 Health Survey Scale - Mental Health |
3.9 | 0.001 sig |
Summary
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT00423592). 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.