NBI-98854 Dose Titration Study for the Treatment of Tardive Dyskinesia

This is a Phase 2, randomized, double-blind, placebo-controlled, dose-titration study to
evaluate the efficacy, safety, and tolerability of NBI-98854 (titrated to subject's optimal
dose in the range of 25 to 75 mg) compared to placebo, administered once daily (q.d.) for a
total of 6 weeks of treatment. Approximately 90 medically stable male and female subjects
with one of the following clinical diagnoses will be enrolled: schizophrenia or
schizoaffective disorder with neuroleptic-induced TD; mood disorder with neuroleptic-induced
TD; or gastrointestinal disorder with metoclopramide-induced TD.

For subjects randomized to active treatment, the starting dose will be 25 mg NBI 98854,
which may be escalated in increments of 25 mg every 2 weeks to a maximum of 75 mg to achieve
an optimal dose of NBI-98854 for each subject

Inclusion Criteria:

- Have one of the following clinical diagnoses for at least 3 months prior to screening
a) schizophrenia or schizoaffective disorder; b) mood disorder; or c)
gastrointestinal disorder (e.g., gastroparesis, gastroesophageal reflux disease)

- Have a clinical diagnosis of neuroleptic-induced tardive dyskinesia for at least 3
months prior to screening.

- Be receiving a stable dose of antipsychotic medication for a minimum of 30 days
before study start. Subjects who are not using antipsychotic medication must have
stable psychiatric status.

- Have the doses of concurrent medications and the conditions being treated be stable
for a minimum of 30 days before study start and be expected to remain stable during
the study.

- Subjects of childbearing potential must agree to use hormonal or two forms of
nonhormonal birth control during the study.

- Female subjects must not be pregnant.

- Be in good general health and expected to complete the clinical study as designed.

- Have a body mass index (BMI) of 18 to 38 kg/m2 (both inclusive).

- Have a negative urine drug screen (negative for amphetamines, barbiturates,
benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids) at screening and
study start, except for any subject receiving a stable dose of benzodiazepine.

- Have a negative alcohol breath test at screening and study start.

Exclusion Criteria:

- Have an active clinically significant unstable medical condition within 1 month (30
days) prior to screening.

- Have a history of substance dependence or substance (drug) or alcohol abuse within
the 3 months before study start(nicotine and caffeine dependence are not
exclusionary).

- Have a known history of neuroleptic malignant syndrome.

- Have a significant risk of suicidal or violent behavior.

- Receiving any excluded concomitant medication such as reserpine, metoclopramide,
stimulants, or tetrabenazine.

- Receiving medication for the treatment of tardive dyskinesia.

- Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface
antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a
history of positive result.

- Have received an investigational drug within 30 days before screening or plan to use
an investigational drug (other than NBI-98854) during the study.

- Have an allergy, hypersensitivity, or intolerance to tetrabenazine.

- Have had previous exposure with NBI-98854.