A COMPARATIVE, OPEN-LABEL, RANDOMIZED, 2 PERIODS, 2 SEQUENCES CROSSOVER STUDY TO ASSESS THE RELATIVE BIOAVAILABILITY OF SODIUM OXYBATE FOR EXTENDED RELEASE ORAL SUSPENSION (FT218) FORMULATION (SINGLE DOSE ADMINISTERED AT THE DOSE OF 6 G) VERSUS THE MARKETED REFERENCE XYREM® (AT THE DOSE OF 2*3 G) IN HEALTHY VOLUNTEERS

FT218 is a new compound that may eventually be used for the treatment of
narcolepsy. Narcolepsy is a sleeping disorder that involves excessive daytime
sleepiness. For some people with narcolepsy it also involves a sudden loss of
muscle tone (cataplexy), usually triggered by strong emotion. Sodium
oxybate/GHB is a substance that has depressant or sedating effects in people.
Xyrem® is an oral solution that has to be taken at bedtime, and then again 2.5
to 4 hours later. This dosing schedule is considered inconvenient for the
patients because they have to wake up in the middle of the night to take the
second dose. FT218 contains the same active molecule or substance (sodium
oxybate) as Xyrem®, but in a special formulation which provides slower and
longer release of the active substance. As a result, FT218 only has to be taken
once at bedtime. FT218 is in development and is not registered as a drug, but
it has been given to humans before.

FT218 is made of the active ingredient sodium oxybate encapsulated in very
small particles made of naturally occurring substances (polymers). Flamel has
conducted all research and studies needed to show that the particles used can
be broken down by the human body and that the components are not harmful. These
particles have been used previously in humans without any safety concern.

FT218 is a new formulation (composition) of the registered drug sodium oxybate.
Sodium oxybate (also known as the sodium salt of gamma-hydroxybutyric acid
[GHB]) is registered under the name Xyrem® for the treatment of narcolepsy. The
purpose of this study is to investigate how safe the new compound FT218 is when
it is administered to healthy subjects in a single dose of 6 g.

It will also be investigated how quickly and to what extent FT218 is absorbed
and eliminated from the body (this is called pharmacokinetics), this will be
compared to 2 doses, 4 hours apart, of the reference product Xyrem® (2*3 g).

The study will be performed in 2 periods. During the study the volunteers will
receive FT218 (6 g) in one period in the evening (around 22:00 h) of Day 1, 2
hours after completion of a standard dinner, as an oral drink (a suspension) of
50 milliliters (Treatment A). After administration of the study compound, the
dosing cup will be rinsed once with 20 milliliters of water, which they will
also be required to drink. They will receive Xyrem® in the other period
(Treatment B). The first dose Xyrem® (3 g) will take place in the evening
(around 22:00 h) of Day 1, 2 hours after completion of a standard dinner, as an
oral drink (a suspension) of 60 milliliters. The volunteers will receive the
second dose (3 g) 4 hours later.
One of the investigators will inspect the mouth after the study compound intake.

During the study they will receive standard meals and snacks at scheduled
times. In-between meals and snacks only water is allowed and no other food or
drinks. From 1 hour before until 1 hour after administration of the study
compound they are not allowed to drink water (except for the water given with
the study compound).

The order in which they will receive FT218 or Xyrem® will be determined by
chance. A total of 14 volunteers will receive FT218 in Period 1 and Xyrem® in
Period 2, and 14 other volunteers will receive Xyrem® in Period 1 and FT218 in
Period 2.

Not applicable

Pain, minor bleedings, bruises and possibly an infection.