Assessment of next-morning driving performance after middle of the night administration of zolpidem tartrate sublingual tablet 3.5 mg in healthy adult volunteers: single-center, double-blind, randomized, placebo-controlled, four-way crossover study

Ideally, a hypnotic administered in the middle-of-the-night by individual
having sleep maintenance problems would allow them to return to sleep rapidly
and wake up with minimal residual sedating effects. As shown in previous
studies, zolpidem tartrate sublingual tablet 3.5 mg appears to be a possible
candidate for middle-of-the-night administration. It is, however, not known
whether this hypnotic still produces residual sedating effects 3 and 4 hours
following administration. Possible residual effects may affect reaction time
and, consequently, impair activities such as driving performance.

The aim of the study is to assess the risk of impaired driving in the morning
at 3 and 4 hours after a middle-of-the-night dose of zolpidem tartrate
sublingual tablet 3.5 mg.

The study is conducted according to a double-blind, randomized,
placebo-controlled, four-way crossover design.

-Single evening administration of zopiclone 7.5 mg, followed by single
middle-of-the-night administration of placebo
-Single evening administration of placebo, followed by single
middle-of-the-night administration (04:15 or 05:15 hours) of zolpidem tartrate
sublingual tablet 3.5 mg
-Single evening administration of placebo, followed by single
middle-of-the-night adminstration of placebo

Subjects will visit the study centre for four test periods, each consisting of
an evening, a night and following morning (in total 12 hours, including 8 hours
of sleep for each period). During these test periods, subjects are administered
a hypnotic or placebo at bedtime and in the middle-of-the-night. The following
morning the residual effects on driving performance are investigated by means
of a highway driving test.
Before and during test periods, use of medication, alcohol, caffeine, and
nicotine is restricted: From one week prior to medical examination en test
periods use of medication that may affact driving performance is not allowed;
from 24 hours prior to a test period no alcohol; from 16:00 hours, untill the
end of the test the next morning no caffeine containing beverages (e.g. coffee,
cola, tea) or food (e.g. chocolate); no smoking during a test period.
Prior to the test periods subjects will be medically examined. This will take
approximately 1 hour and a total of 12 mL blood will be drawn for clinical
blood analysis. In addition, the driving test will be trained during 1 hour and
subjects sleep one night for habituation to the environment and practice of the
procedures. This habituation procedure lasts approximately 10 hours. Following
the final test period again 12 mL blood will be drawn for clinical blood
analysis.
There will be no noticeable risk for participation to this study. Side effects
such as daytime sleepiness, loss of muscle tone, dizziness, tiredness and
blurred vision may occur. Possible minor side-effects are intestinal problems,
increased appetite, decreased libido, and menstrual pains. Alle side-effect are
known to be mild and transient. Zopiclone 7.5 mg is known to impair driving
performance untill 11 hours after administration.