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

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of NBI-98854 in Adult 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 8 weeks of treatment. This study will enroll approximately 90 male and female 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): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States
    • National City, California, United States
    • San Bernardino, California, United States
    • San Diego, California, United States
    • Upland, California, United States
  • Florida
    • Gainesville, Florida, United States
    • Hialeah, Florida, United States
    • Saint Petersburg, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Massachusetts
    • Boston, Massachusetts, United States
    • Natick, Massachusetts, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New Hampshire
    • Nashua, New Hampshire, United States
  • New Jersey
    • Summit, New Jersey, United States
  • New York
    • Albany, New York, United States
    • Manhasset, New York, United States
    • New York, New York, United States
    • Staten Island, New York, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Pennsylvania
    • Norristown, Pennsylvania, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Dallas, Texas, United States
    • Irving, Texas, United States
  • Utah
    • Orem, Utah, United States
    • Salt Lake City, Utah, United States
  • Washington
    • Kirkland, Washington, United States
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• 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. Have a negative urine drug screen for amphetamines, barbiturates, benzodiazepine, phencyclidine, cocaine, or opiates, 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 tachy-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 known history of substance dependence, substance (drug) or alcohol abuse
7. Have a significant risk of suicidal or violent behavior
8. Are currently pregnant or breastfeeding
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
11. Have a blood loss ≥550 mL or donated blood within 30 days prior to screening

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; Placebo administered once daily for 8 weeks	Drug: Placebo
Experimental: Dose Group 1; Fixed dose administered once daily for 8 weeks	Drug: NBI-98854
Experimental: Dose Group 2; Fixed dose administered once daily for 8 weeks	Drug: NBI-98854

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 8 in the YGTSS 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 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression of Change Tourette Syndrome (CGI-TS)-Improvement Score at Week 8	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 8
Change From Baseline to Week 8 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 8
Change From Baseline to Last Visit 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 subjects who discontinued prior to Week 8.	Baseline, Week 8
Change From Baseline to Week 8 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 8
Change From Baseline to Week 8 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 maximum possible total score is 36.	Baseline, Week 8

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: October 19, 2015
• First Submitted That Met QC Criteria: October 19, 2015
• First Posted (Estimate): October 21, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: April 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-98854-1505