An open-label, multiple dose, randomized, two-way crossover study to evaluate the effects of BGG492 on the pharmacokinetics and pharmacodynamics of a monophasic oral contraceptive in healthy female volunteers

BGG492 is not registered as a medicine and is a drug that is being developed
for the treatment of epilepsy. Epilepsy is one of the most common neurological
disorders, with a life time prevalence in excess of 1% of the world population.
Despite the fact that there are several anti-epileptic drugs on the market,
there is still a high medical need for improved treatments of epilepsy since
about 30-40% of patients is inadequately controlled or suffer from drug side
effects. The development of anti-epileptic drugs with new mechanisms of action
is therefore desirable.

BGG492 is a so called orally active AMPA receptor antagonist of which means
that it works on blocking certain signaling proteins in the brain. BGG492 is
showing anticonvulsant activity in several animal models of epilepsy and first
positive results in the interim analysis of an ongoing a single dose proof of
concept trial in patients with light sensitive epilepsy.

The purpose of this investigation is:
• To examine how the new drug BGG492 (study medication) will be absorbed,
metabolized and excreted by the body in combination with the contraception pill
which consists of ethinyl-estradiol and levonorgestrel.
• To assess the effect of BGG492 given on the effect of an oral contraceptive
determined by the hormones FSH, LH, estradiol and progesterone concentrations
and transvaginal ultrasound.
• To assess the safety and tolerability of BGG492 given three times daily in
co-administration with once daily dosing oral contraceptive
• To assess the cardiac safety after repeated administration of BGG492 given
three times a day

This trial is an open label, randomized, two way cross-over study

24 healthy female test subjects will participate in this trial. Depends on the
allocation to the treatment group these 24 women will receive either 1 tablet
of OC given concomitanly with 3 hard gelatine capsules of BGG492 given three
times a day in dose of 100 mg for a period of 21 days in period 1 or period 2.
Alternatively they will receive only OC tablet

So far, four clinical studies with BGG492 were conducted in a total of 247
healthy subjects. The results of these clinical studies regarding safety and
therein observed unwanted events (side effects) as dizziness, fatigue,
sleepiness and balance disorder. In some subjects, changes in their ECG
(electrocardiogram) occurred at different time points after the administration
of BGG492. These were for example a slower heart beat or additional heart
beats of mild intensity that were recorded by the ECG, but induced no
symptoms.

All these described unwanted effects in previous clinical studies were
temporary and disappeared without any treatment. No clinically significant
deviations of vital signs (blood pressure, pulse), ECG (measurement of the
electrical heart activity) or the physical and neurological examination were
reported.

In another clinical study, an interaction between BGG492 and the marketed drug
cyclosporine was investigated in 30 healthy subjects. Reported were the
already known neurological unwanted effects of BGG492. No increase of unwanted
effects with a combined administration of cyclosporine was reported.

Currently, three (3) patient studies are conducted in the indications epilepsy
and migraine. In general, BGG492 was tolerated well. However, in a currently
ongoing proof-of-concept study [CBGG492A2204] investigating a single dose of
250 mg BGG492 in patients with acute migraine, one female patient developed
nystagmus along with dizziness and unsteady gait 4 hours after intake of study
medication. All events resolved 3 hours after onset. Nystagmus had been
observed for the first time and in this case it was classified as serious since
the patient was hospitalized overnight for observation, i.e. the event was
classified as a suspected unexpected serious adverse event (SUSAR).