Clinical Trial: A Study to Test the Safety of Combined Dosing With Aminophylline and Ambrisentan in Exercising Healthy Human Volunteers at Simulated High Altitude

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

Official Title: A Randomized, 4-Sequence, Double-Blind Study to Test the Safety of Combined Dosing With Aminophylline and Ambrisentan in Exercising Healthy Human Volunteers at Simulated High Altitude

Brief Summary: Acute exposure of the unacclimatized human body to high altitude leads to health complications, such as loss of exercise performance capacity and fatigue. The investigators have found that the combination of the xanthine drug theophylline and the endothelin receptor antagonist ambrisentan improves the exercise performance capacity of rats under simulated high altitude. In young, healthy human volunteers, this combination of drugs has not increase toxicity over the single compounds under sea-level conditions. The aim of this study is to test whether the combination of theophylline, supplied as its more soluble formulation aminophylline, and ambrisentan, are also safe to take under simulated high altitude of 4,267 meters, under both resting and exercising conditions. The study also aims to test whether this drug combination improves exercise capacity in humans. In this study, human subjects will be randomized to one of four treatment sequences and receive the same study drug(s) throughout all procedures. The study consists of an initial exercise test, followed by two cycles of drug testing at simulated high altitude: Cycle 1 - resting subjects receiving study drug at simulated altitude and continually monitored for safety with pharmacodynamic and pharmacokinetic assessments; and Cycle 2, the same as Cycle 1, with the addition of exercise testing. It is hypothesized that the combination of aminophylline and ambrisentan is not only safe under simulated high altitude, but also improves exercise performance capacity, in comparison with placebo.

Detailed Summary:
Sponsor: Robert J Noveck, M.D.

Current Primary Outcome:

• The safety of combined or single-dose aminophylline and ambrisentan at simulated high altitude in resting human subjects [ Time Frame: Safety endpoints will be measured during an episode of simulated high altitude (Cycle 1), at least 7 days post screening ]
  Incidence and severity of Adverse Events, blood pressure, heart rate, ECGs, blood oxygen saturation (pulse oximetry), symptoms related to early acute mountain sickness (AMS)
• The safety of combined or single-dose aminophylline and ambrisentan at simulated altitude in exercising human subjects [ Time Frame: Safety endpoints will be measured during simulated high altitude (Cycle 2) at least 22 days post screening ]
  Incidence and severity of Adverse Events, blood pressure, heart rate, ECGs, blood oxygen saturation (pulse oximetry), symptoms related to acute mountain sickness (AMS)

Original Primary Outcome: Same as current

Current Secondary Outcome:

• The efficacy of combined aminophylline and ambrisentan to improve exercise capacity under simulated high altitude [ Time Frame: Drug effects on exercise capacity are assessed during an episode of simulated high altitude (Cycle 2), at least 22 days after screening ]
  Exercise capacity is measured as the self-chosen level of exercise burden during cycling on a bicycle ergometer
• The influence of simulated high altitude on pharmacokinetic profiles and drug interaction of aminophylline and ambrisentan [ Time Frame: Blood samples for drug interaction analysis are acquired during an episode of simulated high altitude (Cycle 1), at least 7 days past screening ]
  PK profiles will be compared between combined and single-dosed subjects

Original Secondary Outcome: Same as current

Information By: Duke University

Dates:
Date Received: February 10, 2013
Date Started: September 2013
Date Completion:
Last Updated: November 11, 2015
Last Verified: November 2015