An open-label, randomized, crossover, phase 1 study to evaluate bioequivalence and relative bioavailability between JZP-507 commercial scale and pilot oral solutions in healthy subjects

The JZP-507 oral solution is a new investigational compound that is being
evaluated for the treatment of narcolepsy. Narcolepsy is a sleeping disorder
that involves excessive daytime sleepiness. Some people may also experience a
sudden loss of muscle tone usually triggered by strong emotions (cataplexy).
One of the current medications for excessive daytime sleepiness and cataplexy
in narcolepsy is Xyrem® (sodium oxybate, also known as the sodium salt of
gamma-hydroxybutyric acid [GHB]). This is an oral solution that contains a high
amount of sodium at the highest approved dose. Sodium oxybate/GHB is a
substance that has depressant or sedating effects in people.

JZP-507 is a new oral solution that contains the same active substance as
Xyrem, but reduces the daily intake of sodium. JZP-507 is in development and is
not registered as a drug but has been given to humans before (also referenced
as *KEY-507 D*).

During the study, an oral solution of JZP-507 produced on a commercial scale
will be compared with a JZP-507 oral solution produced on a pilot scale (an
oral solution of JZP-507 which is manufactured locally at PRA). The purpose of
the study is to evaluate if the different methods to make the two JZP-507 oral
solutions will affect how quickly and to what extent oxybate is absorbed and
eliminated from the body (this is called pharmacokinetics). This comparison is
called the relative bioavailability. The safety of the JZP-507 oral solutions
and to what extent the JZP-507 oral solutions are tolerated will also be
investigated.

Day 1 is the first day of administration of JZP-507. The volunteer is expected
at the clinical research center in Groningen (location UMCG) at 14:00 h in the
afternoon prior to the day of first administration of the study compound. The
volunteer will be required not to have consumed any food or drinks during the 4
hours prior to arrival in the clinical research center (with the exception of
water).

Each treatment with JZP-507 is separated by a period of 1 day. The volunteer
will receive the investigational compounds on Day 1 and Day 3. During the study
the volunteer will stay for 5 days (4 nights: from Day -1 to Day 4) in the
clinical research center.

On the final study day (Day 4) the volunteer will undergo a post study
screening, during which the volunteer will get similar examinations as in the
pre-study screening (please refer to Chapter 10 of the information booklet). If
the participation in the study is ended earlier than Day 4, he/she will be
asked to undergo the post-study screening to make sure the volunteer is healthy
when he/she leaves the clinical research center.

The participation in the entire study, from pre-study screening until the post
study screening, will be maximally 26 days.

During each treatment the volunteer will receive a solution of 9 mL JZP-507,
diluted with 60 mL of water.

The study consists of 2 treatments with JZP-507 which will be administered
after 10 hours of overnight fasting. The order in which the volunteer will
receive the treatments will be determined by chance to match one of two
predefined sequences. The volunteer will receive each treatment once.

Please refer to the table below to see the planned treatments:

Treatment How often
A 9 mL (3.7 g) JZP 507 commercial scale product Once
B 9 mL (3.7 g) JZP 507 pilot product Once

All drugs have the potential to cause adverse events. The active substance in
JZP-507 is the same as the active substance in Xyrem (oxybate). In a previous
clinical study, 4 variants of the oral solution with JZP-507 (under the former
drug name *KEY 507 D*) were compared to Xyrem. In this study, 35 healthy
volunteers received JZP-507 at the same dose as used in the current study (3.7
g oxybate or 4.5 g Xyrem). No serious adverse events or discontinuations due to
adverse events were reported with any of the treatments. Most of the adverse
events were of mild severity, none were of severe intensity. The following
adverse events were reported by >=5% of the volunteers treated with JZP-507:
somnolence, dizziness, nausea, headache, euphoric mood, vomiting, muscle
contracture, back pain, musculoskeletal stiffness, and paraesthesia (tingling
and prickling sensation). The adverse events reported after treatment with the
JZP-507 oral solution were comparable to those reported after treatment with
Xyrem.

In clinical studies with Xyrem in subjects with narcolepsy, the most common
side effects (those that occurred in greater than or equal to 5% of subjects)
were nausea, dizziness, vomiting, sleepiness, enuresis (inability to control
urination especially during sleep), and tremor (muscle twitching).

In clinical studies with Xyrem in healthy volunteers, vomiting was seen in
approximately 24% of those who received 4.5 g Xyrem while fasting. Less common
side effects with Xyrem that occurred in greater than or equal to 2% but less
than 5% of subjects were diarrhea, stomach pain, dry mouth, pain, feeling
drunk, edema peripheral (swelling of legs), pain in arms and legs, increased
cataplexy in people with cataplexy (a sudden loss of muscle tone usually
triggered by strong emotion), muscle spasms, paresthesia (tingling and
prickling sensation), disturbance in attention (cannot concentrate), sleep
paralysis (not able to move when falling asleep or at awakening),
disorientation (loss sense of direction, position), anxiety (feeling of worry),
irritability (easily annoyed), sleep walking, and hyperhidrosis (sweating a
lot).

The rare but serious side effects (that occurred in less than 2%) in
Xyrem-treated subjects were reduced or stopped breathing, sleep apnea (short
periods of no breathing while sleeping), loss of consciousness or coma,
psychosis (seeing or hearing things that are not real), and thoughts of killing
yourself or trying to kill yourself.

As with taking any drug, there is a risk of allergic reaction. Some symptoms of
allergic reactions are: rash, difficulty breathing, and wheezing, sudden drop
in blood pressure, a fast heart rate sweating, and swelling around the mouth,
throat or eyes. During your stay in the research center you will be monitored
continuously for any symptoms of an allergic reaction.

As information becomes available, the volunteer will be told of any changes in
the way the study will be done and of any newly identified risks to which the
volunteer may be exposed that may affect the willingness to participate in the
study. The following adverse effects may occur in relation to the
investigational procedures:

Blood Drawing Risks: Risks associated with drawing blood from the arm include
lightheadedness, pain, bruising, and bleeding at the site of needle puncture,
inflammation of the vein, and, on rare occasions, infection. Scarring damage to
a vein is also possible.

IV risks: During the placement of an IV catheter into a vein, the volunteer may
experience pain and/or bruising at the site on the arm where the IV is placed
and blood is taken. In the event the IV fails to work properly, a direct needle
stick into a vein may obtain blood draws for one or more time-points. The
volunteer may experience dizziness, lightheadedness, and/or fainting. Localized
bruising, clot, and infections may occur. Scarring damage to a vein is also
possible.

ECG Risks: Risks associated with ECG may include skin irritation, redness, and
itching from the adhesive pads.