An Open-Label, Long-Term Safety Study Including a Double-Blind, Placebo-Controlled, Randomized Withdrawal Period of TEV-50717 (Deutetrabenazine) for the Treatment of Tourette Syndrome in Children and Adolescents
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 228
- 试验地点
- 76
- 主要终点
- Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
研究概览
简要总结
This is an otherwise open-label, single-arm study that includes a 2-week, double-blind, placebo controlled, randomized drug withdrawal period followed by a 3 week blinded maintenance or re-titration, and then a maintenance period. This study aims to evaluate the safety and efficacy of TEV-50717 tablets in patients with tics associated with TS who have previously completed participation in any of the parent studies.
详细描述
This is an otherwise open-label, single-arm study (Part A) that includes a 2-week, double-blind, placebo controlled, randomized drug withdrawal period (Part B) followed by a 3 week blinded maintenance or re-titration (Part A resumed), and then a maintenance period. This study aims to evaluate the safety and efficacy of TEV-50717 tablets in patients with tics associated with TS who have previously completed participation in any of the parent studies (SD-809-C-17 [Phase 1b], TV50717-CNS 30046 [Phase 2/3], or TV50717-CNS 30060 [Phase 3]).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Patient is younger than 18 years of age on day 1
- •Patient weighs at least 44 pounds (20 kg)
- •The patient's active tics are causing distress or impairment
- •Patient is able to swallow study medication whole
- •Patient is in good general health
- •Women/girls of childbearing potential whose male partners are of childbearing potential must use contraception for the duration of the study -- Additional criteria apply, please contact the investigator for more information
排除标准
- •Patient is 18 years of age or older.
- •Patient has a neurologic disorder other than TS that could obscure the evaluation of tics.
- •The patient's predominant movement disorder is stereotypy (coordinated movements that repeat continually and identically) associated with autism spectrum disorder.
- •Patient has a confirmed diagnosis of bipolar disorder, schizophrenia, or another psychotic disorder.
- •Patient has clinically significant depression at screening or day
- •Note: Patients receiving antidepressant therapy may be enrolled if on a stable dose for at least 6 weeks before screening.
- •Patient has a history of suicidal intent or related behaviors within 2 years of screening
- •Patient has a history of a previous actual, interrupted, or aborted suicide attempt.
- •Patient has a first-degree relative who has completed suicide.
- •Patient has clinically significant obsessive-compulsive disorder (OCD) on day 1 that, in the opinion of the investigator, is the primary cause of impairment.
- •Patient has received comprehensive behavioral intervention for tics for TS or cognitive behavioral therapy for OCD within 4 weeks of screening.
- •Patient has received treatment with deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation for reduction of tics within 4 weeks of the screening visit.
- •Patient has an unstable or serious medical illness at screening or day 1
- •Patients with a history of torsade de pointes, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
- •Patient has received a monoamine oxidase inhibitor within 14 days of the day 1 visit.
- •Patient has participated in an investigational drug or device study (with the exception of Study SD-809-C-17, Study TV50717-CNS-30046, or Study TV50717-CNS-30060) and received IMP/intervention within 30 days or 5 drug half-lives of day 1, whichever is longer.
- •The patient is a pregnant or lactating female, or plans to become pregnant during the study.
- •Patient has a history of, or acknowledges, alcohol-related disorder in the previous 12 months -- Additional criteria apply, please contact the investigator for more information
研究组 & 干预措施
TEV-50717- Part A
All patients will undergo TEV-50717 dose titration in this study. Patients will receive 6 mg of TEV-50717 with food on the evening of day 1. The titration scheme and maximum dose will be determined by body weight and cytochrome P450 2D6 (CYP2D6) impairment status from the parent study.
干预措施: TEV-50717 (Drug)
TEV-50717- Part B RW
TEV-50717 is administered during Part B Randomized Drug Withdrawal (RW) 2-week period.
干预措施: TEV-50717 (Drug)
Placebo- Part B RW
Placebo is administered during Part B Randomized Drug Withdrawal (RW) 2-week period only.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) for Parts A & B Combined
时间窗: Day 1 to Week 55
Adverse events were analyzed for all participants in Parts A \& B combined as one group for this outcome measure. An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Incudes clinically significant changes such as changes in vital signs or lab values. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants Reporting Treatment Emergent Adverse Events (AEs) in Part B (Period II)
时间窗: Weeks 28 to 30
Adverse events were analyzed for Part B for this outcome measure. An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Incudes clinically significant changes such as changes in vital signs or lab values. Relationship of AE to treatment was determined by the Investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score
时间窗: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
Parents were asked to rate their child's behaviors in past 2 weeks on a 4-point Likert scale from "not at all" to "much or most of the time." It contains 2 subscales (emotional problems and functional problem). Total score: sum of 2 subscales, ranging from 0 to 51, with higher score indicating more depression-related behaviors.
Change From Baseline in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score
时间窗: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
CDI-2 self-report: 28-item questionnaire assessing depressive symptoms in children 7 to 17 years of age with basic reading and comprehension skills. Children were asked to choose 1 of 3 statements that most closely aligns with their feelings in past 2 weeks. It contains 6 subscales (emotional problem, negative mood/physical symptoms, negative self-esteem, functional problems, ineffectiveness, interpersonal problems). Total score: sum of all subscales scores, ranging from 0 to 56, with higher score indicating greater depression severity.CDI-2 parent: 17-item questionnaire administered to parents to assess depression-related behaviors observed in their children.
Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Parent Version) Total Score at Week 30
时间窗: Week 28, Week 30
Parents were asked to rate their child's behaviors in past 2 weeks on a 4-point Likert scale from "not at all" to "much or most of the time." It contains 2 subscales (emotional problems and functional problem). Total score: sum of 2 subscales, ranging from 0 to 51, with higher score indicating more depression-related behaviors.
Change From Randomized Withdrawal Baseline (Week 28) in the Children's Depression Inventory Second Edition (CDI-2; Self-reported Version) Total Score at Week 30
时间窗: Week 28, Week 30
CDI-2 self-report: 28-item questionnaire assessing depressive symptoms in children 7 to 17 years of age with basic reading and comprehension skills. Children were asked to choose 1 of 3 statements that most closely aligns with their feelings in past 2 weeks. It contains 6 subscales (emotional problem, negative mood/physical symptoms, negative self-esteem, functional problems, ineffectiveness, interpersonal problems). Total score: sum of all subscales scores, ranging from 0 to 56, with higher score indicating greater depression severity.CDI-2 parent: 17-item questionnaire administered to parents to assess depression-related behaviors observed in their children.
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: Baseline, Weeks 2, 4, 8, 15, 28, 34, 41, 54, 55
C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in following 10 categories: 1 = Wish to be dead; 2 = Non-specific active suicidal thoughts; 3 = Active suicidal ideation with any methods (not plan) without intent to act; 4 = Active suicidal ideation with some intent to act, without specific plan; 5 = Active suicidal ideation with specific plan and intent; 6 = Preparatory acts or behavior; 7 = Aborted attempt; 8 = Interrupted attempt; 9 = Non-fatal suicide attempt; and 10 = Completed suicide. Number of participants with any suicidal ideation or suicidal behavior are reported. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module.
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS) at Randomized Withdrawal Baseline Visit (Week 28) and Week 30
时间窗: Week 28, Week 30
C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in following 10 categories: 1 = Wish to be dead; 2 = Non-specific active suicidal thoughts; 3 = Active suicidal ideation with any methods (not plan) without intent to act; 4 = Active suicidal ideation with some intent to act, without specific plan; 5 = Active suicidal ideation with specific plan and intent; 6 = Preparatory acts or behavior; 7 = Aborted attempt; 8 = Interrupted attempt; 9 = Non-fatal suicide attempt; and 10 = Completed suicide. Number of participants with any suicidal ideation or suicidal behavior are reported. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module.
次要结局
- Change From Baseline in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)(Baseline, Weeks 8, 15, 28, 41, 54, and 55)
- Change From Baseline in the Tourette Syndrome-Clinical Global Impression (TS-CGI) Score(Baseline, Weeks 8, 15, 28, 41, 54, and 55)
- Change From Baseline in the Tourette Syndrome-Patient Global Impression of Impact (TS-PGII) Score(Baseline, Weeks 8, 15, 28, 41, 54, and 55)
- Change From Baseline in the Child and Adolescent Gilles de la Tourette Syndrome - Quality of Life (C&A-GTS-QOL) Activities of Daily Living (ADL) Subscale Score(Baseline, Weeks 6, 28, 34, 54)
- Change From Randomized Withdrawal Baseline (Week 28) in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS) to Week 30(Week 28, Week 30)