A PHASE I, OPEN-LABEL, FIXED-SEQUENCE, THREE-PERIOD CROSSOVER TRIAL TO EVALUATE THE PHARMACOKINETICS OF TWO DIFFERENT TABLET FORMULATIONS OF BCI 952 COMPARED TO THE OVER-ENCAPSULATED BCI-952 PRODUCT COMPONENTS IN HEALTHY MALE SUBJECTS

BCI-952 is a new combination of two registered medications, buspirone and
melatonin SR (slow release), that may eventually be used for the treatment of
Major Depressive Disorder (MDD). Buspirone is a psychoactive drug and is
generally used for the treatment of anxiety disorders. Melatonin is generally
prescribed as a sleep aid. Until now, BCI-952 was administered in other
studies as two separate capsules. BrainCells Inc has developed two new
formulations of BCI-952 tablets, so that a single tablet contains buspirone as
well as melatonin SR. Both tablets contain the same amount of buspirone and the
same amount of melatonin. The two tablets also contain the same additive;
however, the proportion of the additives differs between the two new
formulations. An additive is an inactive substance which is added to the drug
to create volume and make it possible to form a tablet. The additives may also
affect the slow release nature of the melatonin.
This new combination of registered medications is not registered as a drug but
has been given to humans before.

Primary
To evaluate the pharmacokinetics of two different tablet formulations of
BCI-952 compared to the over-encapsulated BCI-952 product components.

Secondary
To evaluate the safety and tolerability following the administration of two
different tablet formulations of BCI-952 and the over-encapsulated BCI-952
product components.

Design
An open-label, fixed sequence, three-period crossover study in eight healthy
male subjects receiving a single oral dose of BCI 952 in 3 different
formulations (two new tablet formulations compared to the over encapsulated
tablets/caplets of two separate components). For each individual subject, there
will be a washout of at least five days between dosing in each period.

Procedures and assessments
-Screening and follow-up:clinical laboratory, physical examination, 12-lead ECG
(in triplicate), vital signs (including pulse rate, systolic and diastolic
blood pressure, respiratory rate and oral body temperature); at eligibility
screening: medical history, drug screen, HBsAg, anti HCV, anti-HIV 1/2; to be
repeated upon each admission: 12-lead ECG, vital signs and clinical laboratory
(including drug screen)

-Observation period:three periods in clinic from -18 h up to 24 h after drug
administration on Day 1

-Blood sampling:for pharmacokinetics of plasma melatonin and buspirone:
pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16 and 24 h post
dose

-Safety assessments:adverse events: throughout the study; vital signs
(including pulse rate, systolic and diastolic blood pressure, respiratory rate
and oral body temperature): pre-dose and 1, 4, 12 and 24 h post-dose

-Bioanalysis:analysis of melatonin and buspirone samples using a validated
method by PRA

Treatments
Period 1: a single dose of BCI-952 consisting of an over-encapsulated
commercially available buspirone IR 15 mg tablet and an over-encapsulated
commercially available melatonin SR 3 mg caplet
Period 2: a single oral dose of BCI-952 new formulation #F8, containing
buspirone IR 15 mg and melatonin SR 3 mg as a single bi-layer tablet
Period 3: a single oral dose of BCI-952 new formulation #F13, containing and
buspirone IR 15 mg and melatonin SR 3 mg as a single bi-layer tablet

Study medication: BCI-952
Active substance:buspirone and melatonin
Activity: neurogenesis
Indication:depression
Strength:15 mg buspirone IR and 3 mg melatonin SR
Dosage form:single bi-layer tablet or over-encapsulated tablet/caplet

Procedures: pain, light bleeding, heamatoma, possibly an infection