Pharmacokinetics and metabolism of [14C]BMS-820836 in healthy male subjects

The drug to be given is a new, investigational compound that may eventually be
used for the treatment of depression and anxiety disorders.
Depressive Disease is defined as a depressive disorder characterized by
depressed mood, loss of either interest or pleasure, loss of energy, must have
persisted for at least two weeks, associated with significant impairment in
functioning. Anxiety disorders is a blanket term covering several different
forms of abnormal and pathological fear and anxiety.
Depression and Anxiety disorders are thought to be caused by a malfunctioning
in the brain of certain proteins (monoamines like noradrenalin, serotonin and
dopamine). The study drug is a potent, and selective triple monoamine reuptake
inhibitor which is acting on the three monoamines mentioned before.

Primary:
- to assess the pharmacokinetics of the study drug and total radioactivity
(TRA) and the routes and extent of excretion of drug-derived material after
administration of a single 3 mg oral dose of 14C- labeled study drug in healthy
male subjects

Secondary:
- to assess the safety of a single oral 3 mg dose of [14C]-BMS-820836

Exploratory:
- to identify metabolites of BMS-820836 (and, if applicable, estimate their
exposures)
- to identify routes of elimination of BMS-820836

Design:
an open-label, non-randomized, single dose study in six healthy male subjects
receiving a single oral dose of 14C-labeled study drug containing
approximately 2.95 MBq (80 µCi) of total radioacarbon

Procedures and assessments
Screening and follow-up:
The screening will include a physical examination including measurement of
blood pressure, pulse rate, body temperature and respiratory rate, a heart
trace (electrocardiogram) recording, and a number of blood and urine tests.
Subjects will also be screened for drugs of abuse, Hepatitis B and C, and HIV
(= AIDS test).

Observation period:
one period in clinic from -17 h up to 336 h (Day 15) after drug administration
with a possible extension to Day 22 if the following discharge criteria are not
met: at least 90% of the total dose of radioactivity has been collected and the
measurement of combined radioactivity in a 24-hour interval collection of urine
and feces is * 1% of the administered radioactivity over the prior 3
consecutive days (based on [14C] radioactivity quick counts)

Blood sampling:
- for pharmacokinetics of the study drug in plasma: pre-dose and 2, 4, 6, 7, 9,
12, 24, 48, 72, 96, 120, 144, 192 and 336 h post dose dose and in case
subjects are required to stay in the unit past Day 15 based on the discharge
criteria for radioactivity recovery: 504 h post-dose
- for total radioactivity in plasma: pre-dose and 2, 4, 6, 7, 9, 12, 24,48, 72,
96, 120, 144, 168, 192, 216, 240, 264, 288, 312 and 336 h post-dose and in case
subjects are required to stay in the unit past Day 15 based on the discharge
criteria for radioactivity recovery: 360, 384, 408, 432, 456, 480 and 504 h
post-dose

Urine sampling:
for pharmacokinetics, total radioactivity and biotransformation: pre-dose and
intervals 0-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192,
192-216, 216-240, 240-264, 264-288 and 288-312 h post-dose and then every 24 h
interval until discharge

Faeces sampling:
for total radioactivity and metabolite profiling : pre-dose and intervals 0-24,
24-48, 48-72, 72-96, 96-120, 120-144, 144-168, 168-192, 192-216, 216-240,
240-264, 264-288 and 288-312 h post-dose and then every 24 h interval until
discharge

Safety assessments:
adverse events: throughout the study; physical examination: once on Day 1;
vital signs and ECG: 6 h post-dose and once at discharge; body weight and
clinical laboratory:once at discharge

Bioanalysis:
analysis of plasma and urine study drug samples using a validated method by
Sponsor
analysis of total radioactivity in whole blood, plasma, urine and faeces using
a validated method by Sponsor
quick counts by PRA
metabolite profile in plasma, urine and faeces using a validated method by
Sponsor

Active substance: BMS-820836 and [14C]-BMS-820836

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