An open label, sequential study to assess the drug-drug interaction of Divalproex Sodium extended release (ER) at steady-state on FT218 formulation administered at a single 6 g dose in healthy volunteeers

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 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.

Divalproex sodium ER has been on the market as a drug for the treatment of
epilepsy, mania / bipolar disorder and migraine. It is already known that the
pharmacokinetics of Xyrem® is affected by divalproex sodium ER.

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 the influence of the compound
divalproex sodium extended-release (ER) on the absorption, distribution, and
elimination (this is called pharmacokinetics) of FT218 from the body, when it
is administered to healthy participants. This study will indicate if divalproex
sodium ER affects the concentrations of FT218 in the blood. FT218 has been
administered to humans before. Divalproex sodium ER is not a new compound; the
active component valproate is already available on the market in several
dosages and formulations.

It will also be investigated whether FT218 given without and with divalproex
sodium ER is safe.

The actual study will consist of 1 period during which the volunteers will stay
in the research center in Groningen Martini Hospital for 14 days (13 nights).

Day 1 is the first day of administration of the study compound. The volunteers
are expected at the research center at 14:00 h in the afternoon prior to the
day of first administration of the study compound. They will leave the research
center on Day 13 of the study.

During the study they will receive 6 gram (g) of FT218 as an oral drink (a
suspension) of 50 milliliters (mL). After administration of the study compound,
the dosing cup will be rinsed once with 20 mL of water, which will also be
required to drink. During the study they will also receive 1250 milligram (mg)
of divalproex sodium ER as oral tablets with 240 mL of water. One of the
investigators will inspect the hands and mouth after the study compound intake.

FT218 and/or divalproex sodium ER is administered in the morning, 2 hours after
they have started a breakfast. After administration of the study compound(s),
the volunteers will be required to fast for 4 additional hours on Day 1, Day 11
and Day 12. Then they will be served lunch. During fasting they are allowed to
drink water, except during 1 hour before and 1 hour after administration of the
study compound.

Not applicable.

Pain, minor bleedings, bruises and possibly an infection.