Effects of Single Dose of Bilastine 20mg on Flying Ability in Healthy Volunteers Under Conditions of Simulated Cabin Pressure

Rationale: Optimal physical and mental fitness of the pilots is a prerequisite
for flight safety. Pilots suffering from allergic rhinoconjuctivitis or other
allergic diseases are not allowed to fly because ambient pressure changes may
aggravate the symptoms and some antihistaminic medication may interfere with
flight safety, probably due to their sedative effects. Bilastine is a new
second-generation highly selective H1 antihistamine that has been developed for
the treatment of allergic rhinoconjunctivitis and urticaria. Bilastine is
considered to have no sedative side effects and no cardiotoxic effects and may,
therefore, provide a safe therapeutic alternative to keep pilots suffering from
allergic rhinitis on flying status. A single oral dose of bilastine 20 mg had
minimal brain H1 receptor occupancy, was not associated with subjective
sedation or objective impairment of psychomotor performance and driving
ability, and was devoid of treatment-related sedative adverse effects, thus
satisfying relevant subjective, objective criteria as a non-sedating
antihistamine. Although 20 mg bilastine produced no significant impairment of
cognitive and psychomotor performance, it should be excluded that the drug may
affect flying abilities of pilots working in an airliner cabin environment with
lowered ambient pressure.

Objective: The response over time on daytime alertness and performance will be
assessed following a single oral dose of bilastine 20 mg in healthy volunteers
performing flying ability tests in a hypobaric chamber with an ambient pressure
of 75.2 kPa, which equals an airliner cabin altitude of about 8,000 feet.

Study design: This will be a single-center, randomized, double-blind,
placebo-controlled, crossover study using single doses of bilastine 20 mg,
placebo, and hydroxyzine 50 mg as an active control.

Intervention: In a crossover design all subjects will receive bilastine 20 mg,
hydroxyzine 50 mg, and placebo on three respective treatment days. There will
be at least a seven-day washout between each treatment day.

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Volunteers have to visit the institute for
screening, training on the tasks, and familiarization in the hypobaric chamber
(total 0.5 day) and have to undergo the assessments on 3 separate trial days.
Each trail day lasts 8 hours of which 7 hours are spent in the hypobaric
chamber with an ambient pressure equalling the cabin pressure of an airliner.
Under these circumstances peripheral oxygen saturation may decrease by 5-10%,
which is known to be easily tolerable without health complaints. Reported
adverse effects of bilastine are headache, somnolence, dizziness, and abdominal
pain (all infrequent, mild and with an incidence not different from placebo).
Reported adverse effects of the active control hydroxyzine are dry mouth,
drowsiness, sleepiness, dizziness, hypotension, headache, allergic reactions,
pruritus, rash, urticaria, and hallucinations. It is anticipated that all
reported adverse effects recover spontaneously after termination of the
treatment. It is considered that the possible adverse effects of the study
medication and/or hypobaric conditions are non-health threatening and
acceptable. The outcome of the study may provide a safe therapeutic alternative
for pilots suffering from allergic rhinitis, or urticaria.