Ecopipam Treatment of Tourette Syndrome

Tourette's Syndrome is a neurological disease characterized by verbal and motor tics.
Although its causes are unknown, many researchers believe that changes in brain chemicals
(called neurotransmitters) are critically involved. One of these neurotransmitters is called
dopamine, and it exerts its actions through its receptors (called D1-type or D2-type). It
has been suggested that the symptoms of Tourette's Syndrome are due to an overactivity at
the D1-type receptor. Ecopipam is a selective antagonist of the D1-type receptors. The
present clinical trial is designed to test if ecopipam is able to relieve the symptoms of
the disease in adults patients with Tourette's Syndrome. Eligible patients will be treated
for eight weeks.

Inclusion Criteria:

- Subjects must have TS (Tourette's Syndrome) based on the clinician-administered DCI
(Diagnostic Confidence Index) for TS.

- Subjects must exhibit both motor and vocal tics.

- Subjects must have exhibited tics for >5 years.

- Subjects must have a minimum score of 20 at both Screening and Baseline (just prior
to the first treatment) on the YGTSS (Yale Global Tic Severity Score).

- Subjects must be age ≥ 18 years.

- Women must be postmenopausal (> 12 months without menses) or surgically sterile
(i.e., by hysterectomy and/or bilateral oophorectomy) or must be using effective
contraception (i.e., oral contraceptives, intrauterine device, double barrier method
of condom and spermicide) and agree to continue use of contraception for the duration
of their participation in the study. Women of childbearing potential must agree to
use contraception for 30 days after their last dose of study drug.

- Sexually active male subjects must use a barrier method of contraception during the
study and agree to continue the use of male contraception for at least 30 days after
the last dose of study drug.

- Subject must execute a written informed consent.

Exclusion Criteria:

- Subjects who have unstable medical illness or clinically significant abnormalities on
laboratory tests, or ECG at Screening.

- Subjects with a major depressive episode in the past 2 years

- Subjects with a history of attempted suicide

- Subjects with clinically significant suicidality (score of ≥ 2 on Item 3 for the
Hamilton Depression Rating Scale [HAM-D])

- Subjects with a first-degree relative with a major depressive episode that resulted
in any psychiatric hospitalization, attempted or completed suicide

- Subjects with a history of seizures.

- Subjects with a myocardial infarction within 6 months.

- Women of childbearing potential who are currently pregnant or lactating.

- Subjects who have a need for medication (other than ecopipam) with possible effects
on TS symptoms (i.e., lithium, naltrexone, methylphenidate, or psychostimulants),
unfavorable interactions with ecopipam (ie, dopamine agonists [including bupropion]),
or monoamine oxidase inhibitors.

- Subjects with a lifetime history of bipolar disorder type I or II, dementia,
schizophrenia, or any psychotic disorder determined by the Structured Clinical
Interview for Diagnostic Statistical Manual IV Text Revision (DSM-IV-TR) Axis-I
Disorders (SCID).

- Subjects with current or recent (past 3 months) DSM-IV substance abuse or dependence
(with the exception of nicotine).

- Subjects with positive urine drug screen (cocaine, amphetamine, methamphetamine,
tetrahydrocannabinol (THC), benzodiazepines, barbiturates, phencyclidine (PCP),
opiates) at Screening. Subjects with urine positive only for benzodiazepines and/or
marijuana (i.e., a user but not an abuser as based on DSM-IV criteria) may be
eligible.

- Subjects who have had previous treatment with ecopipam.

- Subjects who have had treatment with:

- investigational medication or depot neuroleptics within 3 months

- fluoxetine within 6 weeks

- other psychotropics with possible effects on TS symptoms (ie, lithium, or
naltrexone) within 2 weeks prior to Screening.

- oral neuroleptics within 2 weeks

- selective serotonin reuptake inhibitors unless the dosage has been stable for a
minimum of 4 weeks prior to study start