A phase I, open-label, randomized, three-way cross-over study to determine the relative bioavailability of an oral capsule formulation, given both in the fasted state and after a high fat meal, compared to an oral suspension of PSN821 in healthy male volunteers.

The study drug to be given, PSN821, is a new experimental drug (study drug)
that could potentially be a beneficial treatment for type 2 Diabetes. Type 2
Diabetes is a disease characterized by the presence of a high level of sugar
(glucose) in the blood (hyperglycaemia). Type 2 Diabetes patients have an
increased risk of, for example, blindness, kidney (renal) dysfunction and heart
or blood vessel (cardiovascular) complications. The prevalence of type 2
Diabetes is high and is growing at an alarming rate. The number of adults with
Diabetes in the world is expected to reach 300 million by the year 2025, with
more than 90% having type 2 Diabetes. PSN821 interacts with a protein called
GPR119 that occurs naturally in the body. GPR119 is a member of the G-protein
coupled receptor family, and is found mainly in the gut (gastrointestinal
tract) and pancreas. It is involved in the secretion of hormones such as GLP-1
and insulin, and may therefore affect blood glucose levels and body weight. In
laboratory experiments, results have been obtained that suggest that PSN821 may
possibly lower blood glucose levels, food intake, and body weight, which could
be of importance in the treatment of type 2 Diabetes. In addition PSN821 can
also be administered through the mouth (orally). This new drug is still in
development and is not registered as a drug.

Primary:
- to determine the relative bioavailability of a solid formulation (capsule) of
PSN821 compared with an oral suspension of the drug.

Secondary :
- to determine the effect of food on to determine the effect of a high fat meal
or light breakfast on exposure and pharmacokinetics of PSN821 and its
metabolite PSN715297 when PSN is administered as a capsule
- to further evaluate the safety and tolerability of PSN821 in the fasted state
(oral suspension and capsule) and in the fed state (oral capsule)

Design:
A single centre, open-label, randomized, three-way cross-over study in sixteen
lean healthy male subjects. Subjects will each receive 4 doses of PSN821 listed
below in a randomized open-label three-way crossover study design. Subjects
will be assigned to randomization block ABCD, BCAD or CABD, with 4 subjects per
randomization block.

Treatment A: Single oral dose of 375 mg of PSN821 as a suspension in the fasted
state
Treatment B: Single oral dose of 375 mg of PSN821 as a capsule in the fasted
state
Treatment C: Single oral dose of 375 mg of PSN821 as a capsule after consuming
a standard high fat breakfast
Treatment D: Single oral dose of 375 mg of PSN821 as a capsule after consuming
a light breakfast

There will be a minimum of 6 days between doses. There will be an ambulant
visit on Day 3 of each period.
All subjects will return for a follow-up visit 5 to 10 days after their final
dose.



Procedures and assessments
Screening and follow-up:
Clinical laboratory (including clinical chemistry, haematology and urinalysis),
physical examination (including body weight and Body Mass Index (BMI)
calculation), vital signs (including supine and standing systolic and diastolic
blood pressure and pulse rate), 12 lead electrocardiogram (ECG), adverse events
(AEs) and previous and concomitant medication
Screening: demographics, height, medical history, drug and alcohol screen,
HBsAg, anti-HCV and anti-HIC *.
Drug and alcohol screen and previous and concomitant medication to be repeated
upon each admission.

Observation period:
Four periods in clinic each being from 17 hours before to 24 hours after drug
administration, with an ambulant visit at 48 hours after drug administration.

Blood sampling:
For pharmacokinetics (PK) of PSN821 and its metabolite PSN715297 in plasma:
pre-dose, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 and 48 hours
post-dose.

Safety assessments:
AEs: throughout the study; vital signs (including supine and standing systolic
and diastolic blood pressure, and pulse rate): at screening, at pre-dose
(triplicate), at 1, 2, 4 and 24 hours post dose and at follow-up; ECG: at
screening, at pre-dose (in-triplicate) and 1, 2, 4 and 24 hours post-dose and
at follow up; clinical laboratory (including clinical chemistry, haematology
and urinalysis): at screening, pre-dose and at 24 and 48 hours post-dose and
follow-up; drug and alcohol screen: at 48 hours post-dose.

Study Medication
Active substance: PSN821
Activity: GPR119 agonist
Indication: Type 2 Diabetes mellitus
Strength: 50 mg/g (oral suspension) / 375 mg (oral capsule)
Dosage form: oral suspension/oral capsule

Treatment
Treatment A: Single oral dose of 375 mg of PSN821 as a suspension in the fasted
state
Treatment B: Single oral dose of 375 mg of PSN821 as a capsule in the fasted
state
Treatment C: Single oral dose of 375 mg of PSN821 as a capsule after consuming
a standard high fat breakfast
Treatment D: Single oral dose of 375 mg of PSN821 as a capsule after consuming
a light breakfast

In a previous study in 41 healthy volunteers, with doses up to 3000 mg, the
following adverse effects were reported: nausea, headache and dizziness. These
adverse events were all mild and only the minority was considered to be
possibly related to the study medication

The insertion of the indwelling canula and the venepuncture may cause some
pain, and sometimes lead to a
bruise, but the actual collection of blood will not be painful. Light bleeding
and possibly an infection may
occur. However, these complications are rare.