An Open-Label, Long-Term Safety Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 343
- 试验地点
- 82
- 主要终点
- Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal
研究概览
简要总结
The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of SD-809 in reducing the severity of abnormal involuntary movements of moderate to severe tardive dyskinesia. The purpose of part B is to establish the durability of effect of SD-809 following 1-week period of randomized withdrawal (SD-809 and placebo), followed by 12 weeks of maintenance with SD-809.
详细描述
Participants who complete study SD-809-C-18 (NCT02195700), SD-809-C-23 (NCT02291861), or any other SD-809 study will be enrolled in this study. This study include a screening period (Part A), a titration period (Part A), a long-term treatment period (Part A), a double-blind, randomized withdrawal period (Part B), treatment after completion of the randomized withdrawal period (Part B), and a post-treatment safety follow-up period (Part A and Part B). EU participants who complete Part B will be invited to participate in Part C.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of using a dopamine receptor antagonist for at least 3 months
- •Clinical diagnosis of tardive dyskinesia and has had symptoms for at least 3 months prior to screening
- •Participant has successfully completed a controlled study of SD-809 for treatment of moderate to severe tardive dyskinesia
- •Participants with underlying psychiatric diagnosis are stable and have no change in psychoactive medications
- •Have a mental health provider and does not anticipate any changes to treatment regimen in the next 3 months
- •History of being compliant with prescribed medications
- •Able to swallow study drug whole
- •Be in good general health and is expected to attend all study visits and complete study assessments
- •Female participants must not be pregnant and agree to an acceptable method of contraception
排除标准
- •Currently receiving medication for the treatment of tardive dyskinesia
- •Have a neurological condition other than tardive dyskinesia that may interfere with assessing the severity of dyskinesias
- •Have a serious untreated or undertreated psychiatric illness
- •Have recent history or presence of violent behavior
- •Have unstable or serious medical illness
- •Have evidence of hepatic impairment
- •Have evidence of renal impairment
- •Have known allergy to any component of SD-809 or tetrabenazine
- •Has participated in an investigational drug or device trial (other than Study C-18, Study C-23, or any other eligible TEV-50717 parent study) and received study drug within 30 days
- •Have acknowledged use of illicit drugs
- •Have a history of alcohol or substance abuse in the previous 12 months
研究组 & 干预措施
Part A: SD-809
Participants will receive SD-809 orally twice daily (BID) starting at 12 mg/day, which will be titrated based on dyskinesia control and tolerability up to a maximum total dose of 48 mg/day. Participants who decline to participate in Part B, will continue at their stable dose of SD-809 BID up to Week 158.
干预措施: SD-809 (Drug)
Part B: Placebo
Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks.
干预措施: SD-809 (Drug)
Part B: Placebo
Participants will receive placebo matched to SD-809 for 1 week in randomized withdrawal period and thereafter will receive SD-809 (stable dose) for 12 weeks.
干预措施: Placebo (Drug)
Part B: SD-809
Participants will receive SD-809 (stable dose) for 1 week in randomized withdrawal period and will continue to receive the same dose of SD-809 for an additional 12 weeks.
干预措施: SD-809 (Drug)
Part C: SD-809
EU participants who complete Part B and willing to continue in the study will continue treatment with SD-809 for 52 weeks at the dose administered during the 12-week open-label period of Part B.
干预措施: SD-809 (Drug)
结局指标
主要结局
Part A, B, and C: Number of Participants With Treatment-Emergent AEs (TEAEs), Serious TEAEs, Severe TEAEs, Drug-Related TEAEs, and TEAEs Leading to Withdrawal
时间窗: Baseline up to the end of follow-up (4 weeks after the last dose of study drug; mean exposure: up to approximately 866.1 days)
AEs were analyzed as one group combined for parts A and B per planned analysis. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE=prevents normal daily activities. Drug-related TEAEs: TEAEs with possible, probable, or definite relationship to study drug. Serious AEs: death, a life-threatening AE, 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 participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A treatment-emergent AE was defined as an AE that began after the first administration of study medication or existing AEs that worsened after the first dose of study medication. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Part B: Change From Day 1 Visit in Total Motor AIMS Score at Day 7 Visit, as Assessed by Blinded Central Video Rating
时间窗: Day 1 of Part B, Day 7 of Part B
The AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and -scored items. A total motor score from Items 1 to 7 (orofacial, extremity, and truncal movements) was calculated. Items 1 through 7 included facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). Each item was rated on a 5-point anchored scale ranging from 0 (no dyskinesia) to 4 (severe dyskinesia). Total motor AIMS score for Items 1-7 ranged from 0 to 28, with higher scores indicative of more severe dyskinesia.
次要结局
- Part A: Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating(Baseline, Week 145)
- Part A: Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating(Baseline, Week 158)
- Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 145, as Assessed by the Site Rating(Baseline, Week 145)
- Part A: Percent Change From Baseline in Total Motor AIMS Score at Week 158, as Assessed by the Site Rating(Baseline, Week 158)
- Part A: Percentage of Participants Who Had a 50% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating(Baseline to Week 145)
- Part A: Percentage of Participants Who Had a 70% or Greater Reduction From Baseline in Total Motor AIMS Score, as Assessed by the Site Rating(Baseline to Week 145)
- Part A: Change From Baseline in AIMS Items 8, 9, and 10 Score at Week 145, as Assessed by the Site Rating(Baseline, Week 145)
- Part A: Percentage of Participants Who Were a Treatment Success, Based on the Clinical Global Impression of Change (CGIC)(Baseline up to Week 145)
- Part A: Percentage of Participants Who Were a Treatment Success, Based on the Patient Global Impression of Change (PGIC)(Baseline up to Week 145)
- Part A: Change From Baseline in Modified CDQ-24 Score at Week 158(Baseline, Week 158)