AN OPEN-LABEL, SINGLE CENTRE TRIAL TO INVESTIGATE THE MASS BALANCE AND METABOLITE PROFILE OF A SINGLE ORAL DOSE OF AIC090019

The drug to be given is a new investigational compound that may eventually be
used for the treatment of hepatitis B. Chronic hepatitis B virus (HBV)
infection remains a major cause of severe liver disease and premature
liver-related mortality, worldwide. Epidemiologic trials (trial of factors
affecting the health and illness of populations) have indicated that 350 to 400
million persons are infected. 15 to 40% of these infected persons are at risk
for premature mortality from complications of the infection such as liver
failure and liver cancer.
There are presently seven medications for the treatment of hepatitis B
available. These medications suppress the virus. The treatment is, however, not
always successful and some of these medications have severe side effects.
It is expected that the compound contributes to the treatment of patients with
chronic hepatitis by suppressing the virus and, potentially, decreasing the
virus.

Primary:
To evaluate the mass balance of the study medication
To identify the metabolites of the study medication in plasma and excreta
(urine and faeces)
To identify the routes of elimination of the study medication in humans

Secondary
To assess the safety and tolerability of the study medication
To determine the profile of the study medication and its metabolites in humans
in plasma and excreta (urine and faeces)

Design:
This is an open-label, single centre, absorption, distribution, metabolism and
excretion (ADME) trial in 8 healthy male subjects. Subjects will receive 50 mg
unlabeled study medi as an oral solution in the morning of Day 1 spiked with an
oral solution containing a tracer dose of 20 kBq of radio labeled study
medication.

Procedures and assessments
Screening and follow-up:
Clinical laboratory examination (including clinical chemistry, haematology,
coagulation and urinalysis), physical examination (including body weight),
vital signs (including supine systolic and diastolic blood pressure, pulse rate
and oral body temperature), 12 lead electrocardiogram (ECG) and previous and
concomitant medication

Screening:
Demographics, body height, medical history and concomitant diseases, drug and
alcohol screen, HBsAg, anti-HBc, anti HCV and anti-HIV 1/2

Admission:
Oral body temperature, drug and alcohol screen, adverse events (AEs), and
previous and concomitant medication

Observation period:
One period in clinic from -18 h up to 168 h (Day 8) after drug administration,
there will be a follow-up visit 14-21 days after dosing

Blood sampling:
For pharmacokinetics (PK) of the study medication and total radioactivity in
plasma: at pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12,
16, 24, 36, 48, 72, 96, 120, 144 and 168 hours post-dose
For metabolite identification: at 0.5, 1, 3, 6, 12, 24, 48, 72, 96, 120, 144
and 168 hours post-dose
For pharmacogenetics: pre-dose

Urine sampling:
For PK of total radioactivity and metabolite identification: at pre-dose and 0
4, 4-8, 8 12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours
post-dose

Faeces sampling:
For PK of total radioactivity and metabolite identification: at pre-dose and 0
12, 12-24, 24 48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours post-dose

Safety assessments:
AEs: recorded from admission until completion of the follow up visit and
specifically within 1 hour pre-dose and at 1, 2, 4, 12, 24, 48, 72, 96, 120,
144 and 168 hours post-dose; clinical laboratory examinations (including
clinical chemistry, haematology, coagulation and urinalysis): on Day -1 and at
168 hours post-dose; vital signs (including supine systolic and diastolic blood
pressure and pulse rate) and 12 lead ECG: within 1 hour pre-dose and at 1, 2,
4, 12, 24, 48, 72, 96, 120, 144 and 168 hours post-dose; physical examination:
at 168 hours post-dose

Bioanalysis:
analysis of plasma, urine and faeces samples using validated methods by Sponsor
analysis of total radioactivity in plasma, urine and faeces using validated
methods by Sponsor
metabolite identification by Sponsor
genotyping by Sponsor

Active substance: AIC090019 and [14C]-AIC090019

Procedures: pain, light bleeding, heamatoma, possibly an infection.
One serious adverse reaction was reported: erosive gastritis in one subject who
received 50 mg. This event was considered to be mild in intensity and assessed
as possibly related to the trial medication. This was treated (including
prolonged hospitalisation) and during the post-trial examination performed on
Day 14 post dose the subject did not show any clinical findings.