Safety, Pharmacokinetics, and Pharmacodynamics of NBI-98854 in Children and Adolescents With Tourette Syndrome (T-FORCE)

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.

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome
• Intervention / Treatment: Drug: NBI-98854

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States
  • Florida
    • Kissimmee, Florida, United States
    • St. Petersburg, Florida, United States
  • Illinois
    • Naperville, Illinois, United States
  • Missouri
    • St. Louis, Missouri, United States
  • Nebraska
    • Lincoln, Nebraska, United States
  • New York
    • New York, New York, United States
    • Rochester, New York, United States
  • Virginia
    • Petersburg, Virginia, United States
  • Washington
    • Kirkland, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adolescents Dose Group 1; Fixed dose of NBI-98854 administered once daily at 0800 for 14 days.	Drug: NBI-98854
Experimental: Adolescents Dose Group 2; Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the adolescent dose group 1 have been reviewed to ensure there are no safety concerns and that maximum tolerated dose (MTD) has not been reached.	Drug: NBI-98854
Experimental: Adolescents Dose Group 3; Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the adolescent dose group 2 have been reviewed to ensure there are no safety concerns and that MTD has not been reached.	Drug: NBI-98854
Experimental: Children Dose Group 1; Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the adolescent dose group 1 have been reviewed to ensure there are no safety concerns and that MTD has not been reached.	Drug: NBI-98854
Experimental: Children Dose Group 2; Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the children dose group 1 have been reviewed to ensure there are no safety concerns and that MTD has not been reached.	Drug: NBI-98854
Experimental: Children Dose Group 3; Fixed dose of NBI-98854 administered once daily at 0800 for 14 days. Dosing will not commence until all safety and PK results from the children dose group 2 have been reviewed to ensure there are no safety concerns and that MTD has not been reached.	Drug: NBI-98854

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events following dosing with NBI-98854	Up to 21 days
Area Under Curve (AUC) of NBI-98854 and its metabolites following repeated daily doses of NBI-98854	Day 1: predose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose; Day 14: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, 72, 120, 168 hours postdose
Assessment of tic behaviors associated with TS using the Yale Global Tic Severity Scale (YGTSS)	Days 1, 7, 14, and 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of tic behaviors associated with TS using the Rush Video-based Tic Rating Scale (RTRS)	Days 1, 7, 14, and 21
Quantification of the premonitory urge phenomena associated with tics using the Premonitory Urge for Tics Scale (PUTS)	Days 1, 7, 14, and 21
Clinical Global Impression of Tourette Syndrome (CGI-TS)	Days 1, 7, 14, and 21
CogState computerized test to assess cognitive function	Day 1 at predose, 2.5 and 8 hours postdose; Day 14 at 8 hours postdose

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Investigators: Principal Investigator: Chris O'Brien, MD, Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 3, 2014

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: January 5, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: NBI-98854-1403