Ambrisentan improves exercise capacity in phase 3 trial

Ambrisentan, a propanoic acid type-A selective endothelin receptor antagonist, improved exercise capacity and delayed clinical worsening in patients with pulmonary arterial hypertension (PAH) in phase 3 clinical trial results presented at the annual international conference of the American Thoracic Society in San Diego, Calif.

The trial included 192 patients, 65% with idiopathic PAH and 35% with PAH due to connective tissue disease, anorexigen use, or human immunodeficiency virus (HIV). The mean baseline 6-minute walk distance (6MWD) was 348 meters, and 46% of patients were World Health Organization (WHO) functional class 1 or 2 with the remaining patients being functional class 3 or 4.

Patients were randomized to receive 2.5 or 5 mg ambrisentan once daily or placebo for 12 weeks. The primary end point was placebo-corrected 6MWD, and secondary end points were time to clinical worsening and change in WHO functional class, the Borg Dyspnea Index, and results of the SF-36 health survey.

Deterioration in functional class occurred in 18% of placebo patients, 5% of the patients in the 2.5-mg group, and 3% of the patients in the 5-mg group.

Ambrisentan was well tolerated in the trial, with the most frequent adverse event-headache-occurring in 7.8% of those in the 2.5-mg group and 12.7% of those in the 5-mg group, compared with 6.2% in the placebo group.