A SINGLE ORAL DOSE STUDY OF THE SAFETY, TOLERABILITY, AND PHARMACOKINETIC PROFILE OF RADIPRODIL IN ADULT HEALTHY VOLUNTEERS

Radiprodil is a new investigational compound that may eventually be used for
the treatment of convulsions in children under 3 years of age (Infantile spasm,
West syndrome). Radiprodil binds to a protein in the neural cells (the
N-methyl-D-aspartate receptor subtype 2B [NR2B]) and changes the sensitivity of
the protein to a signaling agent (glutamate). As a result a decrease in
uncoordinated muscle contractions (convulsions) is expected. Radiprodil is in
development and is not registered as a drug but has been given to humans
before.

The purpose of the study is to investigate how quickly and to what extent
radiprodil is absorbed and eliminated from the body (this is called
pharmacokinetics). It will also be investigated to what extent radiprodil is
tolerated. In addition, 2 new blood sampling methods, allowing easier blood
sampling in young children, will be tested.This study is not intended to
improve your health, but is necessary for the further development of
radiprodil.

The study will be performed in 1 part. The purpose of the study is to
investigate how quickly and to what extent radiprodil is absorbed and
eliminated from the body (this is called pharmacokinetics). It will also be
investigated to what extent radiprodil is tolerated. In addition, 2 new blood
sampling methods, allowing easier blood sampling in young children, will be
tested.

The study will consist of 1 period during which you will receive 30 mg
radiprodil once. Radiprodil will be given as an oral suspension of 12 mL

Should, in the opinion of the investigators, unacceptable adverse effects
appear, the study will be discontinued.

The possible adverse effects of the investigational procedures (e.g. the use of
the indwelling cannula) are described in Chapter 8 of the information booklet.

All potential drugs cause adverse effects; the extent to which this occurs
differs. radiprodil has been given to 118 healthy volunteers and 332 patients
with neuropathic (nerve) pain The most frequently observed adverse effects in
healthy volunteers were: headache, somnolence (feeling sleepy), dizziness,
disturbance in attention, insomnia, altered mood, oropharyngeal (throat) pain,
and euphoric mood, feeling abnormal, feeling drunk, vision blurred, amnesia,
feeling hot, lethargy, palpitations and tremor. Adverse effects more frequently
observed in patients, but not in healthy volunteers were fatigue, nausea,
increased libido, constipation, decreased appetite, flatulence and increased
heart rate. A few rare but serious adverse events that were assessed as at
least possibly related to radiprodil included balance disorder, mental status
changes, feeling confused and suicidal ideation. One patient with predisposing
risk factors had a transient ischemic attack (mini-stroke). These events were
observed only in patients with neuropathic pain exposed to radiprodil
continuously after more than a week of treatment and were reversible. No
serious adverse events occurred during the prior studies in healthy volunteers.

You should be aware that the aforementioned adverse effects and possibly other,
still unknown adverse effects, may occur during the study. With the single dose
used in this study no serious adverse effects are expected.