Clinical trial NCT00617305
Conditions: Pulmonary Arterial Hypertension
Keywords: ambrisentan PAH combination therapy phosphodiesterase type-5 inhibitor (PDE-5i) cardiovascular endothelin receptor antagonist ERA
Sponsor: Gilead Sciences
Start date: 2008-04-01; Completion date: 2011-07-01
Enrollment: 38 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.

Detailed description:
The primary objective of this study is to evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The secondary objectives of this study are to evaluate the change from baseline in other clinical measures of PAH following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy.

The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated throughout the study. In addition, long-term efficacy will be examined.

Arms: arm 1: Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i; sildenafil or tadalafil). arm 2: Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (sildenafil or tadalafil).
Interventions: intervention 1: Ambrisentan intervention 2: Placebo intervention 3: Sildenafil intervention 4: Tadalafil
Intervention descriptions: intervention 1: Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets. intervention 2: Placebo to match ambrisentan was administered orally once daily. intervention 3: Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets. intervention 4: Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.

Protocol documents: