The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers (GQ01)
This is a Phase I, three period, two sequence, open-label, randomized, crossover study, with the primary objective of testing the safety and tolerability of combined oral doses of aminophylline and ambrisentan in healthy human subjects. The secondary objective is to assess the pharmacokinetic profiles of theophylline (aminophylline) and ambrisentan when administered alone or in combination. It is hypothesized that the combination of these drugs is generally safe, and that no drug interaction can be observed.
High Altitude Pulmonary Hypertension
Drug: Aminophylline plus ambrisentan
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Safety Evaluation of Aminophylline and Ambrisentan When Administered Orally Alone and in Combination to Healthy Volunteers|
- To assess the Number of Participants with Adverse Events after dosing, as a Measure of Safety and Tolerability [ Time Frame: 48 h following each dose ] [ Designated as safety issue: Yes ]
- To assess the pharmacokinetic profiles of theophylline (aminophylline) and ambrisentan when administered alone or in combination [ Time Frame: 24 hours after dosing ] [ Designated as safety issue: No ]PK sample collections for plasma Ambrisentan and Theophylline determinations at 0-hour (pre-dose), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post dose
|Study Start Date:||February 2012|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
|Active Comparator: Aminophylline||
Drug will be administered as a single oral dose of 500mg, followed by a 48h washout period.
|Active Comparator: Ambrisentan||
Drug will be administered as a single dose of 5mg, followed by a 48h washout period
Other Name: Letairis
Experimental: Aminophylline and ambrisentan
Treatment 3: Aminophylline, 500 mg plus Ambrisentan, 5 mg
Drug: Aminophylline plus ambrisentan
Drugs will be given as single doses of 500mg (aminophylline) and 5mg (ambrisentan), followed by a 48h washout period
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
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
|United States, North Carolina|
|Duke Clinical Research Unit|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Robert J Noveck, MD||Duke University|