Clinical Trial: The Safety Evaluation of Drug Combinations Against High Altitude Pulmonary Hypertension

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

Official Title: The Safety Evaluation of Theophylline and Bambuterol 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 theophylline and bambuterol in healthy human subjects. The secondary objective is to assess the pharmacokinetic profiles of theophylline and bambuterol 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 theophylline or bambuterol alone, followed by a 7 day wash out interval. Subsequently, Period III consists of the simultaneous administration of both drugs. All subjects are to be confined to the Oslo University Hospital Research Unit throughout all treatment periods [Study Day 1, 7 and 14]. A sufficient number of healthy adult subjects will be consented in order to enroll 20 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: Theophylline 300 mg.

Treatment 2: Bambuterol 20 mg.

Treatment 3: Theophylline 300 mg plus Bambuterol 20 mg.

After completion of each treatment period, the subjects will proceed to the next period provided no Stopping Rules criteria have been met

Sponsor: Norwegian Armed Forces Medical Service

Current Primary Outcome:

• Adverse Events [ Time Frame: 24 hours after dosing ]
  To assess the Number of Participants with Adverse Events after dosing, as a Measure of Safety and Tolerability
• Pharmacokinetic [ Time Frame: 24 hours after dosing ]

  To assess the pharmacokinetic profiles of theophylline and bambuterol when administered alone or in combination.

  PK sample collections for plasma Theophylline and Bambuterol determinations at 0-hour (pre-dose), and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post dose

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Norwegian Armed Forces Medical Service

Dates:
Date Received: March 27, 2012
Date Started: March 2012
Date Completion:
Last Updated: February 22, 2013
Last Verified: February 2013