An open-label, two-period, fixed sequence study to evaluate the effects of multiple oral doses of AFQ056 on the pharmacokinetics of a monophasic oral contraceptive in healthy female volunteers

The test compound is an experimental (or investigational) drug which has not
been registered as a medicine. This drug is being developed by the Sponsor for
the treatment of Fragile X Syndrome and for some aspects of Parkinson*s
Disease. Fragile X syndrome is a genetic syndrome which results in a spectrum
of characteristic physical and intellectual limitations and emotional and
behavioral features which range from severe to mild in manifestation like
learning difficulties, speech impairments, attention problems and epilepsy.
Parkinson*s disease is a degenerative disorder of the central nervous system
that often impairs the sufferer's motor skills, speech but also other functions
like in Fragile X Syndrome.

The test compound is a so called *metabotropic glutamate receptor 5 inhibitor*
which means that it works on blocking certain signaling proteins in the brain

* To examine how multiple oral doses of the test compound (an experimental
medication) will be taken up by the body, metabolized and excreted by the body
in combination with the oral contraception pill which consists of
ethinyl-estradiol and levonorgestrel.
* To investigate the safety and tolerability of multiple oral doses of the test
compound (the test medication).

This trial is a open-label, two-period, fixed sequence study.

30 healthy female subjects will participate in this trial. On day 1 and 18 an
oral contraceptive tablet will be administered. On day 9, 25mg test compound
will be administered twice daily, on day 10, 50mg test compound will be
administered twice daily, on day 11, 75mg test compound will be administered
twice daily and on on days 12-20 100mg test compound will be administered twice
daily.

The test compound has been previously tested in humans and was generally well
tolerated. The test compound has been administered to humans in eight single
dose studies and in seven multiple dose studies (in total about 500 healthy
subjects and patients). The dosage was between 5 mg and 800 mg, single- and
multiple doses. Safety data and data to adverse events result from these
studies. The highest *well tolerated* dosage which has been given to humans
over several days is 100 mg twice a day.

The most commonly reported adverse events were brain related and included:
headache, dizziness, fatigue, insomnia, feeling drunk, blurred vision,
hypoaesthesia, nausea and euphoric mood. In addition, visual hallucinations or
illusions were also reported in healthy subjects.
In general, the frequency and importance of adverse events tended to diminish
over days in multiple dose studies. Studies on subjects and patients with
multiple doses of 150 mg test compound twice a day have shown a higher number
of adverse events that were central nervous system related. In general no
clinically-relevant, drug-related changes in any ECG parameters, vital signs
(heart rate, blood pressure, body temperature, pulse rate) and laboratory
findings were observed.

The dose level is selected on the basis of research results in animals and
humans. The risk to health at these dose levels is limited but you may
experience one of the above mentioned side-effects or other symptoms not
previously reported. Your health will be closely monitored during the trial to
minimize these risks.

A death of a 77 year old patient with Parkinson's disease during participation
in another study with the test compound was reported. This patient had
received the test compound twice-daily for 18 days. Prior to the first intake
of the test compound the patient had shown an abnormal ECG finding. As there
was no autopsy undertaken, the reason for this death remains unclear. To
maximize your safety throughout the study, thorough cardiovascular monitoring
will be carried out during the study. A transient ischemic attack and
paraesthesias has been recently reported for a 50 year-old female patient with
Parkinson's disease during participation in another study with the test
compound . The patient was reported to have completely recovered.