A Single Dose Study of the Pharmacodynamics, Tolerability, and Pharmacokinetics of GAL-054

GAL-054 is not registered as a medicine. GAL-054 is one of two active
ingredients of doxapram that are present in an equal concentration. It is an
oral and intravenous therapeutic agent for short to intermediate term use that
is being developed to stimulate ventilation in patients with respiratory
impairment, including such conditions as central/drug-induced respiratory
depression, decompensated COPD, and weaning from mechanical ventilation.

The purpose of this trial is:
• to study the effect of a single dose of GAL-054 (the test medication) in
healthy volunteers on the functioning of the body, especially on respiration,
and compare this with the effect of a single dose of doxapram.
• to investigate the single dose tolerability of GAL-054 (the test medication)
in healthy volunteers.
• to evaluate how a single dose of oral as well as intravenous administered
GAL-054 (the test medication) is absorbed, broken-down and excreted by the
body.

This trial is a double-blind, randomized, placebo and active-controlled,
crossover study

24-36 healthy male and female volunteers will participate in this 2-part trial.
Part 1 is a 7-period study. During the first 6 periods approximately 12
subjects will receive a single intravenous infusion of GAL-054 (the test
medication), doxapram or placebo during each confinement period. For GAL-054
one dose of GAL-054 at each of 3 dose levels (15, 50, 150 mg) will be
administered. For doxapram, the subjects will receive 2 of 3 dose levels (30,
100, 300 mg). Placebo will be administered once to every subject. The study
drug will be infused over a 100 minute time period. In Period 7 the subjects
will receive an oral dose of 15 mg GAL-054.

Depending on the outcomes of Part 1, the study will end or continue. The number
of subjects in Part 2 is dependent on the outcome of Part 1, but will at least
be between 12 and 24. Part 2 also consists 7 periods with an identical design
as Part 1. The dose levels of doxapram and GAL-054 in Part 2 are also dependent
on the outcome of Part 1. The dose levels might either be the same as in Part 1
or reduced by *-log for both doxapram (10, 30, and 100 g) and GAL-054 (5, 15,
and 50 mg). The occurrence of Period 7 in Part 2 is dependent on the outcome of
Part 1.

The study will start with a screening visit. During the screening visit
standard medical assessments including safety laboratory tests (blood draw,
urine collection), an alcohol breath test, urine drug screen, a physical
examination, ECG and a vital signs measurement will be performed.

During study the subjects will enter the clinic, will receive 7 medication
formulations, will be asked on a regular basis for possible side effects, blood
will be drawn for safety and PK measurements and the vital signs will be
checked regularly during the 7 confinement periods.

Finally a follow-up examination will be performed. During this visit the
subjects will be asked for possible side effects, blood will be drawn for
safety, the vital signs/ECG will be checked and a physical examination will be
conducted.