Safety, Pharmacokinetics, and Pharmacodynamics of NBI-98854 in Children and Adolescents With Tourette Syndrome

A Phase 1b, Open-Label, Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-98854 in Children and Adolescents With Tourette Syndrome

This is a Phase 1b, open-label, multiple-dose study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of NBI-98854 in a total of 36 pediatric subjects with Tourette syndrome (TS). The study will be conducted in approximately 18 male and female children (6 to 11 years of age) and approximately 18 male and female adolescents (12 to 18 years of age). Both age groups will be divided equally into 3 dosing cohorts with 6 subjects each. Ascending doses will be evaluated as part of a staggered-cohort design. Study drug will be administered in each cohort for 14 consecutive days.

Inclusion Criteria:

1. Have documentation of written informed consent, or written and witnessed assent from the subject and written informed consent from the subject's parent or legal guardian.
2. Be in good general health.
3. Have a Diagnostic and Statistical Manual of Mental Disorders diagnosis of Tourette Syndrome (DSM-IV or -V).
4. Have TS symptoms that impair school, occupational, and/or social function.
5. If medications are being used to treat TS symptoms, must be on stable doses of these medications for a minimum of 30 days before baseline (Day -1), and the medication regimen is expected to remain stable throughout the study period. The use of tetrabenazine to treat TS symptoms is prohibited.
6. Subjects of childbearing potential who do not practice total abstinence must be instructed on the proper use of barrier methods of contraception and agree to use hormonal or two forms of nonhormonal contraception consistently from screening until 30 days after the last dose of study drug.
7. Adolescent subjects (12 to 18 years of age) must have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids. Subjects who are on stable doses of prescribed benzodiazepines, opiates, or psychostimulants are allowed to participate in the study.
8. Adolescent subjects (12 to 18 years of age) must have a negative alcohol breath test.
9. Be willing and able to adhere to the study regimen and study procedures described in the protocol and informed consent/assent forms, including all requirements at the study center and return for the follow-up visit.

Exclusion Criteria:

1. Have an unstable medical condition or chronic disease.
2. Had a medically significant illness within 30 days of screening.
3. Excessive use of tobacco and/or nicotine-containing products.
4. Have a history of substance (drug) dependence or substance or alcohol abuse.
5. Are currently pregnant or lactating.
6. Have a known history of neuroleptic malignant syndrome.
7. Have a known history of long QT syndrome or cardiac tachy-arrhythmia.
8. Have a cancer diagnosis within 3 years prior to screening, with the exception of localized skin cancer or carcinoma in situ of the cervix.
9. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study.
10. Have a significant risk of suicidal or violent behavior.