A RANDOMIZED, SINGLE-CENTER, OPEN-LABEL, 5-WAY CROSSOVER, SINGLE-DOSE BIOAVAILABILITY/BIOEQUIVALENCE COMPARISON OF BRIVARACETAM ORAL TABLETS (10MG, 50MG, 75MG, AND 100MG) AND BRIVARACETAM INTRAVENOUS BOLUS INJECTION (100MG) IN HEALTHY VOLUNTEERS

Brivaracetam (BRV) is a new investigational compound that may eventually be
used for the treatment of epileptic seizures. BRV is not yet approved as a drug
but has been given to humans before.

Primary objective:
To assess the BE under fasted conditions of BRV 10mg, 75mg, and 100mg oral
tablets of commercial formulation vs BRV 50mg oral tablet
(reference) of clinical development formulation,

To assess the BA under fasted conditions of BRV 100mg 2-minute iv bolus
injection vs BRV 100mg oral tablet

Secundary objective:
The secondary objective is to gain additional information about the safety and
tolerability of BRV.

Design:
This is a randomized, single-center, open-label, 5-way crossover, single-dose,
BE/BA Phase 1 study in 25 (planned) healthy subjects.

Procedures and assessments
Screening and follow-up:
clinical laboratory, physical examination, ECG, vital signs, serum pregnancy
test (females only); at eligibility screening: medical history, urine drug and
alcohol screening tests, height, weight, HBsAg, anti HCV, anti-HIV 1/2, FSH
(females only)

Each admission:
vital signs, urine dip-stick pregnancy test (only for females of childbearing
potential)

Observation period:
each period in clinic from up to 48 hrs after drug administration

Blood sampling:
for pharmacokinetics: predose, 5min, 15min, 30min, 1h, 1.5h, 2h, 3h, 6h, 9h,
12h, 24h, 36h, and 48h post dose.

Safety assessments:
Physical examinations, ECG, vital signs, clinical laboratory and AEs.

Strength:
Tablets of 10, 50, 75 and 100 mg; 100mg iv bolus 10mg/mL injection

Dosage form:
Oral Tablets of 10, 50, 75 and 100 mg; 100mg iv bolus 10mg/mL injection using a
syringe and slow push in 2 minutes

The order in which the treatments are given in the 5 periods may differ between
volunteers.

During the investigation, various assessments can be experienced as more or
less stressful.

Blood draw, indwelling canula:
During this study blood will be drawn. Each period 1 time an indwelling canula
will be used and a number of blood draws will be drawn by direct puncture of
the vein. The insertion of the canula may be associated with pain, minor
bleeding, bruising, possible infection.

Also there will be a second canula inserted in the other arm for the
administration of the iv bolus injection. This may be associated with the same
side effects as reported above.

In previous studies with BRV in healthy subjects, the most common adverse
effects tended to appear rapidly after the first study drug intake were
dizziness, a strong desire for sleep, fatigue, feeling drunk, euphoric mood,
headache, nausea, vertigo, lack or loss of strength and energy (weakness). BRV
belongs to a group or *class* of medications known as anti-epileptics. An
increased risk of suicidal ideation (thoughts of harming yourself or committing
suicide). Suicide attempt and completed suicide have been noticed in people who
take anti-epileptic medications and also in people who have a severe or long
term of epilepsy. With the doses used in this study no serious adverse effects
are expected. The occurrence of known or other effects cannot be excluded.