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

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.

Conditions

• Acute Mountain Sickness and Fatigue

Interventions

DRUG

Aminophylline 400 mg

Xanthine derivative

DRUG

Ambrisentan 5 mg

Endothelin receptor antagonist

OTHER

Placebo

Sponsors & Collaborators

• United States Department of Defense

  collaborator FED

• Robert J Noveck, M.D.

  lead OTHER

Principal Investigators

• Robert J Noveck, MD, PhD · Duke University

• Claude A Piantadosi, MD · Duke University

• Thies Schroeder, PhD · Duke University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-09-30

Primary Completion

2014-09-30

Completion

2014-12-31

Countries

• United States

Study Locations