An Open-Label Study to Determine the ADME of 14C-labeled SLV337 after a Single Dose of an Oral Suspension

The drug to be given is a new, investigational compound that may eventually be
used for the treatment of type 2 diabetes mellitus. In type 2 diabetes
mellitus, blood sugar levels. Insulin regulates the blood sugar concentrations.
In type 2 diabetes mellitus, blood sugar concentrations are not regulated
properly by insulin. Therefore blood sugar concentrations can be elevated. The
compound influences for example metabolism, energy management, responses to
insulin, and inflammation. It is expected that the compound may improve the
regulation of blood sugar metabolism and lipid metabolism in the body.

Primary:
Part 1:
- to assess the relative bioavailability of the compound in an oral suspension
(400 mg) and capsules (5 x 200 mg)
- to determine the dose of the compound to be administered as an oral
suspension in Part 2 of the study
Part 2:
- to assess the excretion balance of total 14C-radioactivity after single oral
administration of the14C labeled compound (3.33 MBq, in the range of 400 mg up
to 1000 mg)
- to determine the PK of the compound, the compound acyl-glucuronide and total
14C-radioactivity
- To collect plasma, urine and feces samples containing 14C-labeled parent
compound and
metabolites of SLV337 for metabolic profiling and identification.

Secondary:
Both Part 1 and Part 2
- to collect data on safety and tolerability of single oral doses of the
compound in the form of a suspension and capsule

Design:
An open-label, randomized, two-part study.

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

Observation period:
Part1 :
2 periods, up to a total of 6 days each period
Part 2:
One period up to a total of 9 days.

Blood sampling:
Part 1:
- for pharmacokinetics and acyl-glucuronide in plasma: pre-dose and up to 96
hours post dose
- for genotyping: post dose (period 1 only)

Part 2:
- for pharmacokinetics and acyl-glucuronide in plasma: pre-dose and up to 168 h
hours post dose (if discharge is between Day 5 and Day 8)
- for total radioactivity in plasma and whole blood: pre-dose and up to 168 h
post dose (if discharge is between Day 5 and Day 8)
- for metabolite profiling and identification in plasma: pre-dose and up to 96
h post-dose
- for plasma protein binding and acyl-glucuronide reactivity: pre-dose and 2
and 6 h post-dose
- for genotyping: post dose

Urine sampling:
Part 2 only.
- for total radioactivity and metabolite profiling: pre-dose and intervals 0-4,
4-8, 8-12 and 12-24 h post-dose and thereafter 24 h collection intervals

Faeces sampling:
Part 2 only.
- for total radioactivity and metabolite profiling: pre-dose and thereafter 24
h collection intervals

Safety assessments:
Part 1:
Adverse events: throughout the study; ECG and vital signs: pre-dose and 2 and 6
h post-dose and once on Day 5; clinical laboratory: pre-dose

Part 2:
Adverse events: throughout the study; clinical laboratory: pre-dose; ECG and
vital signs: pre-dose and 2 and 6 h post dose

Bioanalysis:
- analysis of plasma and whole blood and its metabolites samples using
validated methods by Sponsor
- analysis of total radioactivity in plasma, whole blood, urine and faeces
using validated methods by PRA
- metabolite profiling and identification by Sponsor
- plasma protein binding by Sponsor
- genotyping by Sponsor
- quick counts by PRA

Active substance: SLV337 and [14C]-SLV337

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