The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers

This is a Phase I, three period, two sequence, single-center, open-label, randomized, crossover study design. Periods I and II consist of the oral administration of either a single dose of aminophylline or ambrisentan alone, followed by a 48 hour wash out interval. Subsequently, Period III consists of the simultaneous administration of both drugs. All subjects are to be confined to the Duke Clinical Research Unit throughout all treatment periods \[Study Day -1 to Study Day 6 (discharge)\]. A sufficient number of healthy adult subjects will be consented in order to enroll 24 and complete 16 subjects who complete all three periods. Replacement of subjects is permitted, if necessary. Qualified subjects will be randomized into one of two sequences consisting of three Periods as indicated below: -------------Period 1-----Period 2-----Period 3 Sequence A: Treatment 1 Treatment 2 Treatment 3 Sequence B: Treatment 2 Treatment 1 Treatment 3 TREATMENTS: Treatment 1: Aminophylline 500 mg (corresponding to 395 mg theophylline). Treatment 2: Ambrisentan 5 mg. Treatment 3: Aminophylline, 500 mg plus Ambrisentan, 5 mg. After completion of each treatment period, the subjects will proceed to the next period provided no Stopping Rules criteria have been met