A Phase 2, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study to Evaluate the Safety and Efficacy of NBI-98854 in Pediatric Subjects With Tourette Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 81
- 试验地点
- 2
- 主要终点
- Time to Loss of Treatment Response
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
open-label study drug treatment period followed by blinded randomization into treatment arm or placebo arm
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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-
- •Have HIV, hepatitis B, or hepatitis C
研究组 & 干预措施
Pre-randomization 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.
干预措施: Valbenazine (Drug)
Randomized Placebo
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.
干预措施: Placebo oral capsule (Drug)
Randomized 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.
干预措施: Valbenazine (Drug)
结局指标
主要结局
Time to Loss of Treatment Response
时间窗: 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.
次要结局
- Change From Randomization Baseline to the Week 36 Visit in the CGI-Tics-Severity Score(Randomization Baseline (Week 8, 10 or 12); Week 36)
- 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)
- 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)
- Change From Randomization Baseline to the Week 36 Visit in the YGTSS TTS(Randomization Baseline (Week 8, 10 or 12); Week 36)