An outpatient phase 3 efficacy study of Ecopipam (PSYRX 101) in the symptomatic treatment of self-injurious behavior in subjects with Lesch-Nyhan disease.

Ecopipam is an investigational drug, it has not yet been granted marketing
approval by regulatory agencies such as the European Medicines Agency (EMA).
Ecopipam is being investigated for use in the symptomatic treatment of
self-injurious behavior in subjects with Lesch-Nyhan Disease (LND).

LND is a very rare neurogenetic disorder caused by a mutation of the HPRT gene.
It is characterized by uric acid accumulation, intellectual impairment,
movement disorders and self-injurious behavior. Estimates reveal an incidence
of LND of 1 in 235,000 live births and a prevalence of 1 case per million.

D1-receptor super-sensitivity may be a mechanism for the repetitive and
compulsive self-injurious behaviors. Ecopipam is a selective antagonist of the
D1-receptor family. This study aims to assess the efficacy and safety of
Ecopipam in the symptomatic relief of self-injurious behavior in subjects with
LND.

The primary objective of this study is to assess the efficacy of Ecopipam to
reduce self-injurious behaviors (SIB) in adults and children with Lesch-Nyhan
Disease (LND) in an outpatient setting. The secondary objectives of this study
are to assess the effect of withdrawal, maintenance, and safety of Ecopipam in
subjects with LND.

Protocol PSY102 is a multicenter, randomized, double-blind, 3-period crossover
study, with an open-label extension. In an outpatient setting, subjects will be
randomized to receive placebo or Ecopipam as the initial treatment.
Double-blind treatment will occur over a 19 to 20 week period with subjets
receiving 1 of the following 2 sequences: Sequence A - placebo, Ecopipam,
placebo or Sequence B - Ecopipam, Placebo, Ecopipam.

Ecopipam (50 or 100 mg, depending on weight) or matching placebo will be taken
daily at bedtime. Subjects who tolerate double-blind treatment will be allowed
to enter the open-label extension and will receive Ecopipam (50 or 100 mg,
depending on weight) for up to 52 weeks, which will be taken daily at bedtime.

* Double-blind phase
Subjects will receive Ecopipam (50 or 100 mg, based on body weight) or matching
placebo daily at bedtime. No study drug will be administered during the
follow-up period (between treatment period 3 and the start of the open-label
phase).

* Open-label extension phase
Subjects will receive a single daily dose of Ecopipam (50 or 100 mg, based on
body weight) at bedtime.

Currently, there are no medications approved for the treatment of
self-injurious behavior in patients with Lesch-Nyhan Disease. The study aims to
assess the efficacy and safety of Ecopipam in the symptomatic relief of
self-injurious behavior in subjects with Lesch-Nyhan Disease. Ecopipam has been
studied in over 2 thousand human subjects in clinical studies and showed to be
well tolerated. In a study with Ecopipam in subjects with Lesch-Nyhan Disease,
the most common side-effects were: sleepiness, upset stomach and involuntary
muscle movement (dystonia).

The total study duration for a subject will be approximately 17 months (up to
18 weeks double-blind treatment, 1 to 2 week follow-up, followed by up to 52
weeks on open-label extension). At most, 3 clinic visits and 6 home visits will
be performed. Additionally, the caregiver will be contacted every 4 weeks by
telephone during the open-label extension.

During the trial following assessments will be performed (see schedule of
procedures/assessments on page 31 of the protocol):
- Physical examination: 1x
- Vital signs (systolic and diastolic blood pressure, radial pulse,
respiration, body temperature and weight): 9x
- Measurement of height: 1x
- Blood drawing: 3x (total approx. 30 ml)
- Urine sample: 3x
- Pregnancy test (urine): 3x (females of childbearing potential only).

The Behavior Problems Inventory (22x) and Caregiver Global Impression (6x) will
be completed by the caregiver.