A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ASCENDING MULTIPLE DOSE, SAFETY, TOLERABILITY PHARMACODYNAMIC AND PHARMACOKINETIC STUDY OF BCI 838 IN HEALTHY ADULT SUBJECTS

BCI-838 is a new investigational compound that may eventually be used for the
treatment of mood disorders (for example depression). BCI-838 is not registered
as a drug but has been given to humans before.

Primary:
To evaluate the safety and tolerability following oral administration of
multiple doses of BCI-838 in healthy male and female subjects

Secundary:
To determine the pharmacokinetic profile of multiple oral doses of BCI-838 in
healthy male and female subjects
To assess the pharmacodynamic effects of BCI-838 on the central nervous system
using quantitative electroencephalogram (EEG) analysis

A randomized, double blinde, placebo-controlled, multi ascending dose, safety,
pharmacokinetic and pharmacodynamic study of BCI-838 in healthy male and female
adult subjects.

The study will consist of 30 subjects divided over 3 groups (10 subjects per
group). The subjects De vrijwilligers will receive a dose of between 100 to 900
mg BCI-838 in the form of a capsule.
The dose level for group 1 will most likely be 100 mg. However, the exact dose
level will be determined based on ongoing single ascending dose studies. The
dose levels for the subsequent groups (2 and 3) will be increased to a maximum
of 900 mg and only if the lower dose of the previous group was found to be well
tolerated and after receipt of no objection by the local Ethics Committee.

Procedures and assessments during the study:
Screening , follow-up and during study: demographics, body weight and height
(including body mass index calculation),
medical history, drug and alcohol screen, cotinine test, blood sampling for
serology (HBsAg, anti HCV and anti-HIV 1/2),
DNA test, clinical chemistry, hematology, pharmacokinetics, CSSRS, Heart trace
(ECG*s), and registration of brain activity (EEG)

The study will consist of 3 groups, each group will will stay in the clinical
research centre for 11 days (10 nights).
During the study subjects will receive BCI-838 or inactive formulation
(placebo) after a high fat breakfast with 240 mL of tap water once daily on 7
subsequent days. Per group 8 participants will receive BCI-838 and 2
participants will receive placebo. Whether subjects will receive the active
drug or placebo will be determined by chance.
The participant, nor the investigator knows if BCI-838 will be dosed; we call
this *the study is blinded*. However, information on the administration of
study medication and placebo will be present in the clinical research facility,
in sealed envelopes, which can be opened in case of emergency.
The participant will receive the study drug after a high fat breakfast, which
they will need to finish completely. The high fat breakfast will start 30
minutes prior to dosing and will need to be finished 10 minutes prior to
dosing. Sbjects will need to fast (not eat or drink anything) until 4 hours
after drug administration, after which they will receive a lunch. After intake
of the study medication, they are allowed to drink water with the exception of
2 hour prior to until 1 hour after drug administration. After dosing, subjects
are not allowed to lie down for 4 hour post dose, with the exception of study
related procedures.

During the study several assessments will be conducted differing in extent and
the nature of burden:
Blood draws via direct puncture or an indwelling canula: It is anticipated that
for each group 2 time(s) an indwelling canula
will be used and 18 blood draws will be drawn by direct puncture of the vein.
Possible side effects of an indwelling canula are pain, light bleeding,
heamatoma, possibly an infection.

Heart trace (ECG*s): specifically on Days 1 and 7.

Recording of brain activity (EEG) will be performed on days 1 and 7

Columbia Suicide Severity Rating Scale (C-SSRS) will be performed during
screening and follow-up and on Day 7

In previous studies with healthy volunteers, adverse events that were reported
were in general mild, transient and considered not related to study drug. To
date only mild headache is reported as possibly related to the study
medication.