AN OPEN LABEL STUDY TO EVALUATE THE PHARMACOKINETICS OF ASP7035 AFTER A SINGLE ORAL DOSE OF 14C-LABELED ASP7035 IN HEALTHY MALE SUBJECTS

The drug to be given is a new, investigational compound that may eventually be
used for the treatment of excessive night-time urination. The need to get up
during the night in order to urinate is highly associated with for example
aging, medication usage, diabetes mellitus and sleep disturbance. The compound
is expected to reduce urinating by decreasing the water excretion in the
kidneys.
No causal therapy for excessive night-time urination is available. A drug with
a similar mode of action, however, is used at the moment. The drug is expected
to have a better, more predictable efficacy and safety profile.

Primary:
- to evaluate the pharmacokinetics, in particular the routes and extent of
metabolism and excretion, of the study medication after a single oral dose of 1
mg 14C-labeled study medication

Secondary:
-to identify the metabolic profile of the study medication in human, blood,
plasma, urine and feces after a single oral dose of 1 mg 14C-labeled study
medication
-to evaluate safety and tolerability after a single oral dose of 1 mg
14C-labeled study medication

Design:
An open-label ADME study in six healthy male subjects receiving a 14C labeled,
single oral dose of the study medication, containing approximately 2.8 MBq
radioacarbon

Procedures and assessments
Screening and follow-up:
Clinical laboratory, vital signs (in triplicate at screening), physical
examination, 12-lead ECG; at eligibility screening: medical history, alcohol
and drug screen, HBsAg, anti HCV, anti-HIV 1/2; physical examination, alcohol
and drug screen, clinical laboratory, vital signs and 12-lead ECG to be
repeated upon admission

Observation period:
One period in clinic from -17 h up to 120 h after drug administration and a
possible extension to Day 9 if discharge criteria (recovery of administered
radioactivity *95% and radioactivity in urine and faeces is below acceptable
limits <50 dpm/mL in urine or <75 dpm in 100 mg original faeces) have not been
met on Day 6; if after the 3-day prolongation, the discharge criteria have
still not been met, subjects will be requested to continue collecting all their
urine and/or faeces at home

Blood sampling:
For pharmacokinetics of the study medication: pre-dose and up to 48 h post-dose
For total radioactivity in plasma and blood: pre-dose and up to120 h post-dose
and each 24 h in case of prolonged in-house stay
For metabolic profiling: pre-dose and up to 120 h post-dose and each 24 h in
case of prolonged in-house stay
For biobanking: pre-dose

Urine sampling:
For pharmacokinetics of of the study medication, total radioactivity and
metabolic profiling: pre-dose and intervals 0-2, 2-4, 4-8, 8-12, 12-24 h
post-dose and 24 h collection intervals up to discharge

Faeces sampling:
For pharmacokinetics of the study medication, total radioactivity and metabolic
profiling: pre-dose and 24 h collection intervals up to discharge

Expired air sampling:
Pre-dose and up to 120 h post-dose and each 24 h in case of prolonged in-house
stay

Safety assessments:
Adverse events: throughout the study; clinical laboratory, 8, 24 and 120 h
post-dose; vital signs and 12-lead ECG: pre-dose and 2, 8, 24 and 120 h
post-dose

Bioanalysis:
Analysis of the study medication in plasma, urine and faeces samples using
validated methods by PRA
analysis of total radioactivity in plasma, blood, urine, faeces and expired air
using validated methods by PRA
metabolic profiling by PRA

Active substance: ASP7035 and [14C]-ASP7035

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