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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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


Sponsor: Thies Schroeder

Current Primary Outcome:

  • Mean Number of Adverse Events Following Each Dose [ Time Frame: 48 h following each dose ]

    Dosing schedule:

    Aminophylline Alone (Single Dose of 500mg Aminophylline) Ambrisentan Alone (Single Dose of 5mg Ambrisentan) Ambrisentan and Aminophylline (Combined Single Dose of 500mg Aminophylline and 5mg Ambrisentan)

  • Plasma Halflife of Theophylline (Aminophylline) and Ambrisentan When Administered Alone or in Combination [ Time Frame: 24 hours after dosing ]

    Aminophylline Alone (Single Dose of 500mg Aminophylline) Aminophylline in Presence of Ambrisentan (Combined Single Dose of 500mg Aminophylline and 5mg Ambrisentan) Ambrisentan Alone (Single Dose of 5mg Ambrisentan) Ambrisentan in Presence of Aminophylline (Combined Single Dose of 500mg Aminophylline and 5mg Ambrisentan)

    Blood 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

  • Time Until Maximum Plasma Concentration (Tmax) of Theophylline (Aminophylline) and Ambrisentan When Administered Alone or in Combination [ Time Frame: 24h after dosing ]

    Aminophylline Alone (Single Dose of 500mg Aminophylline) Aminophylline in Presence of Ambrisentan (Combined Single Dose of 500mg Aminophylline and 5mg Ambrisentan) Ambrisentan Alone (Single Dose of 5mg Ambrisentan) Ambrisentan in Presence of Aminophylline (Combined Single Dose of 500m

    Original Primary Outcome:

    • 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 ]
    • To assess the pharmacokinetic profiles of theophylline (aminophylline) and ambrisentan when administered alone or in combination [ Time Frame: 24 hours after dosing ]
      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


    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Duke University

    Dates:
    Date Received: February 1, 2012
    Date Started: February 2012
    Date Completion:
    Last Updated: November 28, 2013
    Last Verified: November 2013