Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome

Phase 2, double-blind, placebo-controlled study to assess the safety and efficacy of NBI-98854 administered once daily (qd) for a total of 6 weeks of treatment. This study will enroll approximately 90 male and female pediatric subjects clinically diagnosed with Tourette Syndrome.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Sun City, Arizona, United States
  • Arkansas
    • Springdale, Arkansas, United States
  • California
    • Long Beach, California, United States
    • San Bernardino, California, United States
    • San Diego, California, United States
    • Upland, California, United States
  • Florida
    • Bradenton, Florida, United States
    • Gainesville, Florida, United States
    • Hialeah, Florida, United States
    • Loxahatchee Groves, Florida, United States
    • Melbourne, Florida, United States
    • Orlando, Florida, United States
    • Saint Petersburg, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
    • Naperville, Illinois, United States
  • Kansas
    • Wichita, Kansas, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Natick, Massachusetts, United States
  • Michigan
    • Ann Arbor, Michigan, United States
    • Bloomfield Hills, Michigan, United States
  • Nebraska
    • Lincoln, Nebraska, United States
  • New Hampshire
    • Nashua, New Hampshire, United States
  • New Jersey
    • Marlton, New Jersey, United States
    • Summit, New Jersey, United States
  • New York
    • Manhasset, New York, United States
    • New York, New York, United States
    • Rochester, New York, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Middleburg Heights, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Tennessee
    • Franklin, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Dallas, Texas, United States
    • DeSoto, Texas, United States
    • Fort Worth, Texas, United States
    • Houston, Texas, United States
    • Irving, Texas, United States
  • Utah
    • Orem, Utah, United States
    • Salt Lake City, Utah, United States
  • Washington
    • Kirkland, Washington, United States
    • Seattle, Washington, United States
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Have a clinical diagnosis of Tourette Syndrome (TS)
2. Have at least moderate tic severity
3. Have TS symptoms that impair school, occupational, and/or social function
4. If using maintenance medication(s) for TS or TS spectrum diagnoses (e.g. obsessive-compulsive disorder [OCD], Attention-Deficit Hyperactivity Disorder [ADHD]), be on stable doses
5. Be in good general health
6. Adolescent subjects (12 to 17 years of age) must have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids and a negative alcohol screen
7. Subjects of childbearing potential who do not practice total abstinence must agree to use hormonal or two forms of nonhormonal contraception (dual contraception) consistently during the screening, treatment and follow-up periods of the study

Exclusion Criteria:

1. Have an active, clinically significant unstable medical condition within 1 month prior to screening
2. Have a known history of long QT syndrome or cardiac arrhythmia
3. Have a known history of neuroleptic malignant syndrome
4. Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed)
5. Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors
6. Have a blood loss ≥250 mL or donated blood within 30 days prior to screening
7. Have a known history of substance dependence, substance (drug) or alcohol abuse
8. Have a significant risk of suicidal or violent behavior
9. Have initiated Comprehensive Behavioral Intervention for Tics (CBIT) during the screening period or at baseline or plan to initiate CBIT during the study
10. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Administered once daily for 6 weeks	Drug: Placebo
Experimental: Dose Group 1; Administered once daily for 6 weeks	Drug: NBI-98854
Experimental: Dose Group 2; Administered once daily for 6 weeks	Drug: NBI-98854

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 6 in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)	The YGTSS is designed to rate the overall severity of motor and phonic tic symptoms across a range of dimensions: number, frequency, intensity, complexity, and interference. The YGTSS was administered by the investigator (or qualified designee) using a computer-based structured clinical interview. The TTS is the sum of the 5 motor tic items and the 5 phonic (vocal) tic items and ranges from 0 to 50, with higher scores representing greater severity	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression of Tourette Syndrome (CGI-TS) - Improvement Score at Week 6	The CGI-TS-Improvement scale is used to assess overall improvement since the initiation of study drug dosing on a 7-point scale. Each of the CGI-TS-Improvement response categories was assigned a numerical score as follows: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = Not changed; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.	Week 6
Participants Who Are a YGTSS TTS Responder at Week 6	A TTS responder is defined, on a per-visit basis, as a participant whose TTS value is reduced by at least 30% from baseline at the specified postbaseline visit.	Baseline, Week 6
Change From Baseline to Week 6 in the YGTSS Impairment Score	The YGTSS Impairment item is used to rate impairment due to tics using the following 50-point anchored scale: 0 = None; 10 = Minimal; 20 = Mild; 30 = Moderate; 40 = Marked; 50 = Severe.	Baseline, Week 6
Change From Baseline to Week 6 in the YGTSS Global Tic Severity Score	The YGTSS Global Tic Severity score is the sum of the YGTSS TTS and the YGTSS Impairment score and ranges from 0 to 100, with higher scores representing greater severity.	Baseline, Week 6
Change From Baseline to Week 6 in the Rush Video-based Tic Rating Scale (RTRS) Total Score	A modified RTRS was used in this study that includes short video recordings to measure 5 tic variables: number of body areas affected, frequency of motor and phonic tics, and severity of motor and phonic tics. The RTRS total score is calculated as the sum of the 5 domain scores, and ranges from 0 to 20, with higher scores representing greater severity. The final on-treatment visit was used in participants who discontinued prior to Week 6.	Baseline, Week 6
Change From Baseline to Week 6 in the Premonitory Urge for Tics Scale (PUTS) Total Score	The PUTS is an instrument for quantifying the premonitory urge phenomena associated with tics. It consists of 9 items, each of which is scored on a 4-point scale (1=not at all true, 2=a little true, 3=pretty much true, 4=very much true). The PUTS total score is calculated as the sum of the scores for the 9 items. The total score ranges from 9 to 36, with higher scores indicating a worse outcome.	Baseline, Week 6
Change From Baseline to Week 6 in the Clinical Global Impression of Tics (CGI-Tics) - Severity Score	The CGI-Tics-Severity scale is used to assess overall severity on a 7-point scale. Each of the CGI-Tics-Severity response categories was assigned a numerical score as follows: 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patient.	Baseline, Week 6
Participants Who Are a CGI-TS-Improvement Responder at Week 6	A participant is classified as a CGI-TS-Improvement responder at a given visit if their CGI-TS-Improvement score is either a "1" ("very much improved") or a "2" ("much improved") at the visit.	Week 6

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2016
• Primary Completion (Actual): April 14, 2017
• Study Completion (Actual): April 14, 2017

Study Registration Dates

• First Submitted: February 5, 2016
• First Submitted That Met QC Criteria: February 5, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Actual): January 15, 2021
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: December 1, 2020

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-98854-1501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No