Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome

Phase 2

Terminated

Conditions: Tourette Syndrome

Interventions: Drug: Placebo oral capsule
Drug: Valbenazine

Registration Number: NCT03530293

Lead Sponsor: Neurocrine Biosciences

Brief Summary: This is a Phase 2, double-blind, placebo-controlled, randomized withdrawal study to evaluate the safety and maintenance of efficacy of an optimized once-daily (qd) dose of NBI-98854 in pediatric subjects with TS.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 81

Inclusion Criteria

Have a clinical diagnosis of Tourette Syndrome (TS)
Have at least moderate tic severity
Have TS symptoms that impair school, occupational, and/or social function
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
Be in good general health
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
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

Have an active, clinically significant unstable medical condition within 1 month prior to screening
Have a known history of long QT syndrome or cardiac arrhythmia
Have a known history of neuroleptic malignant syndrome
Have a cancer diagnosis within 3 years prior to screening (some exceptions allowed)
Have an allergy, hypersensitivity, or intolerance to VMAT2 inhibitors
Have a blood loss ≥250 mL or donated blood within 30 days prior to screening
Have a known history of substance dependence, substance (drug) or alcohol abuse
Have a significant risk of suicidal or violent behavior
Have initiated Comprehensive Behavioral Intervention for Tics (CBIT) during the screening period or at baseline or plan to initiate CBIT during the study
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 previously participated in an NBI-98854 clinical study, except for NBI-98854-1403 or NBI-98854-1501.
Have HIV, hepatitis B, or hepatitis C

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Randomized Placebo	Placebo oral capsule	Participants received placebo (matching valbenazine) once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.
Randomized Valbenazine	Valbenazine	Participants received their optimized dose of valbenazine once daily from randomization (Week 8, 10, or 12) through Week 36. Randomization into this arm occurred after treatment with valbenazine once daily through randomization.
Pre-randomization Valbenazine	Valbenazine	Participants received valbenazine once daily for up to 12 weeks, depending on if and when randomization occured. The starting dose was 20 mg for participants \<50 kg at baseline and 40 mg for participants ≥50 kg at baseline, and could be escalated in increments of 20 mg every 2 weeks to a maximum of 60 mg for participants \<50 kg and 80 mg for participants ≥50 kg to achieve an optimal dose of valbenazine for each participant.

Primary Outcome Measures

Name	Time	Method
Time to Loss of Treatment Response	Randomization (Week 8, 10 or 12) through Week 36	Loss of treatment response during the withdrawal period was defined as: 2 consecutive visits with 1) an increase in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) of greater than 35% or 7 points from the randomized withdrawal period baseline and 2) an increase in CGI-Tics-Severity score of ≥2 points from the randomized withdrawal period baseline; or discontinuation due to lack of efficacy or a treatment-emergent adverse event (TEAE) of worsening of tics. Median (lower and upper quartiles) Kaplan-Meier estimates for the time to loss of treatment response were not able to be calculated because of the low incidence of loss of treatment response events.

Secondary Outcome Measures

Name	Time	Method
Change From Randomization Baseline to the Week 36 Visit in the CGI-Tics-Severity Score	Randomization Baseline (Week 8, 10 or 12); Week 36	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.
Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the YGTSS TTS	Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization	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. Least-squares mean were estimated using a mixed-effects model for repeated measures.
Change From Randomization Baseline to the 8 Weeks Post-randomization Timepoint in the CGI-Tics-Severity Score	Randomization Baseline (Week 8, 10 or 12); 8 weeks post-randomization	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.
Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS	Randomization Baseline (Week 8, 10 or 12); Week 36	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.