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

Primary Purpose

Tourette Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NBI-98854
Sponsored by
Neurocrine Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Tourette Syndrome

Eligibility Criteria

6 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Adolescents Dose Group 1

Adolescents Dose Group 2

Adolescents Dose Group 3

Children Dose Group 1

Children Dose Group 2

Children Dose Group 3

Arm Description

Fixed dose of NBI-98854 administered once daily at 0800 for 14 days.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of participants with adverse events following dosing with NBI-98854
Area Under Curve (AUC) of NBI-98854 and its metabolites following repeated daily doses of NBI-98854
Assessment of tic behaviors associated with TS using the Yale Global Tic Severity Scale (YGTSS)

Secondary Outcome Measures

Assessment of tic behaviors associated with TS using the Rush Video-based Tic Rating Scale (RTRS)
Quantification of the premonitory urge phenomena associated with tics using the Premonitory Urge for Tics Scale (PUTS)
Clinical Global Impression of Tourette Syndrome (CGI-TS)
CogState computerized test to assess cognitive function

Full Information

First Posted
September 23, 2014
Last Updated
January 5, 2016
Sponsor
Neurocrine Biosciences
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1. Study Identification

Unique Protocol Identification Number
NCT02256475
Brief Title
Safety, Pharmacokinetics, and Pharmacodynamics of NBI-98854 in Children and Adolescents With Tourette Syndrome
Acronym
T-FORCE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Neurocrine Biosciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tourette Syndrome

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adolescents Dose Group 1
Arm Type
Experimental
Arm Description
Fixed dose of NBI-98854 administered once daily at 0800 for 14 days.
Arm Title
Adolescents Dose Group 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Adolescents Dose Group 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Children Dose Group 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Children Dose Group 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Children Dose Group 3
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
NBI-98854
Primary Outcome Measure Information:
Title
Number of participants with adverse events following dosing with NBI-98854
Time Frame
Up to 21 days
Title
Area Under Curve (AUC) of NBI-98854 and its metabolites following repeated daily doses of NBI-98854
Time Frame
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
Title
Assessment of tic behaviors associated with TS using the Yale Global Tic Severity Scale (YGTSS)
Time Frame
Days 1, 7, 14, and 21
Secondary Outcome Measure Information:
Title
Assessment of tic behaviors associated with TS using the Rush Video-based Tic Rating Scale (RTRS)
Time Frame
Days 1, 7, 14, and 21
Title
Quantification of the premonitory urge phenomena associated with tics using the Premonitory Urge for Tics Scale (PUTS)
Time Frame
Days 1, 7, 14, and 21
Title
Clinical Global Impression of Tourette Syndrome (CGI-TS)
Time Frame
Days 1, 7, 14, and 21
Title
CogState computerized test to assess cognitive function
Time Frame
Day 1 at predose, 2.5 and 8 hours postdose; Day 14 at 8 hours postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Be in good general health. Have a Diagnostic and Statistical Manual of Mental Disorders diagnosis of Tourette Syndrome (DSM-IV or -V). Have TS symptoms that impair school, occupational, and/or social function. 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. 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. 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. Adolescent subjects (12 to 18 years of age) must have a negative alcohol breath test. 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: Have an unstable medical condition or chronic disease. Had a medically significant illness within 30 days of screening. Excessive use of tobacco and/or nicotine-containing products. Have a history of substance (drug) dependence or substance or alcohol abuse. Are currently pregnant or lactating. Have a known history of neuroleptic malignant syndrome. Have a known history of long QT syndrome or cardiac tachy-arrhythmia. Have a cancer diagnosis within 3 years prior to screening, with the exception of localized skin cancer or carcinoma in situ of the cervix. 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 a significant risk of suicidal or violent behavior.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chris O'Brien, MD
Organizational Affiliation
Neurocrine Biosciences
Official's Role
Principal Investigator
Facility Information:
City
San Diego
State/Province
California
Country
United States
City
Kissimmee
State/Province
Florida
Country
United States
City
St. Petersburg
State/Province
Florida
Country
United States
City
Naperville
State/Province
Illinois
Country
United States
City
St. Louis
State/Province
Missouri
Country
United States
City
Lincoln
State/Province
Nebraska
Country
United States
City
New York
State/Province
New York
Country
United States
City
Rochester
State/Province
New York
Country
United States
City
Petersburg
State/Province
Virginia
Country
United States
City
Kirkland
State/Province
Washington
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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