A Phase 2a, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of SAGE-217 in the Treatment of Subjects With Essential Tremor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7
研究概览
简要总结
This study is a three-part, multicenter, Phase 2a study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of SAGE-217 in adult participants with essential tremor.
详细描述
Part A of the study was an open-label design with morning dosing of SAGE-217 for 7 days and included 16 participants, 8 of whom qualified for, and entered, Part B.
Part B had a double-blind, placebo-controlled, randomized withdrawal design with morning dosing for 7 days.
Part C was an open-label design with morning and evening dosing for 14 days and included a different set of 18 participants.
Parts A and B were stopped early (in advance of the planned sample size).
This study was previously posted by Sage Therapeutics. In November 2023, sponsorship of the trial was transferred to Biogen.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must have a diagnosis of Essential Tremor (ET), defined as bilateral postural tremor and kinetic tremor, involving hands and forearms, that is visible and persistent and the duration is >5 years prior to screening.
排除标准
- •Participant has presence of abnormal neurological signs other than tremor or Froment's sign.
- •Participant has presence of known causes of enhanced physiological tremor.
- •Participant has concurrent or recent exposure (14 days prior to admission visit) to tremorogenic drugs.
- •Participant has had direct or indirect trauma to the nervous system within 3 months before the onset of tremor.
- •Participant has historical or clinical evidence of tremor with psychogenic origin.
- •Participant has convincing evidence of sudden tremor onset or evidence of stepwise deterioration of tremor.
研究组 & 干预措施
Part A: SAGE-217 Oral Solution
Participants received SAGE-217 10 mg oral solution on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7 with food in the morning.
干预措施: SAGE-217 (Drug)
Part A: SAGE-217 Capsules
Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2 and 30 mg on Days 3 to 7, orally, with food in the morning.
干预措施: SAGE-217 (Drug)
Part B: Placebo
Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 matching placebo for 7 days beginning on Day 8 with food in the morning.
干预措施: Placebo (Drug)
Part B: SAGE-217 Capsules
Participants who received maximum tolerated dose of SAGE-217 in Part A and achieved response on Day 8 were randomized to receive to SAGE-217 for 7 days beginning on Day 8 with food in the morning.
干预措施: SAGE-217 (Drug)
Part C: SAGE-217 Capsules
Participants received SAGE-217 10 mg capsules on Day 1, 20 mg on Day 2, 30 mg on Day 3, orally, with food in the evening. Beginning on Day 4 through Day 14, participants received a 40-mg total daily dose (administered as 10 mg with food in the morning and 30 mg with food in the evening).
干预措施: SAGE-217 (Drug)
结局指标
主要结局
Part A: Change From Baseline in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 7
时间窗: Baseline (Day 1) and Day 7 (8 hours postdose)
The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Baseline indicates improvement.
Part C: Change From Baseline in the Accelerometer-based Kinesia Upper Limb Tremor Combined Score at Day 15
时间窗: Baseline (Day 1) and Day 15
The accelerometer-based Kinesia upper limb total score is the sum of the individual item scores across both sides of the body. The individual items included forward outstretched postural tremor (FOPT), lateral "wing beating" postural tremor (LWBPT), and kinetic tremor (KT) scores from both sides of the body. Each upper limb individual item question score for each side of the body ranges from 0 to 4. The Kinesia upper limb total score ranges from 0 to 24, with higher scores indicating more tremors/greater tremor amplitude. A negative change from Baseline indicates improvement.
Part B: Change From Randomization in Accelerometer-based Kinesia Kinetic Tremor Combined Score at Day 14
时间窗: Randomization (Day 8, predose) and Day 14 (predose)
The accelerometer-based Kinesia kinetic tremor combined score is the sum of Kinesia kinetic tremor scores across both sides of the body. Tremor is measured using a motion sensor that transmits raw data to a computer where it converts the tremor amplitude to a Kinesia score of 0 to 4 based on validated algorithms; the total score ranges from 0 to 8, higher scores indicate more severe tremor. A negative change from Randomization indicates improvement.
次要结局
- Number of Participants With Clinically Significant Vital Signs(Up to 28 days)
- Parts A and B: Change From Baseline in Stanford Sleepiness Scale (SSS)(Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B)
- Number of Participants With Clinically Significant Laboratory Parameters(Up to 28 days)
- Part A: Change From Baseline in Kinesia Upper Limb Total Score at Day 7(Baseline (Day 1) and Day 7 (8 hours postdose))
- Change From Baseline in the TETRAS Upper Limb Individual Items (Performance Subscale Items 4a, 4b, or 4c) Scores at Day 7(Baseline (Day 1) and Day 7 (8 hours postdose))
- Part B: Change From Randomization in the TETRAS Upper Limb Total Score at Day 14(Randomization (Day 8, predose) and Day 14 (predose))
- Part B: Change From Randomization in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 14(Randomization (Day 8, predose) and Day 14 (predose))
- Part B: Change From Randomization in the TETRAS Performance Subscale Item 4c (Kinetic Tremor) Combined Score at Day 14(Randomization (Day 8, predose) and Day 14 (predose))
- Part B: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Score at Day 14(Baseline (Day 1) and Day 14 (predose))
- Part A: Change From Baseline in Kinesia Upper Limb Individual Item Score at Day 7(Baseline (Day 1) and Day 7 (8 hours [hr] postdose [pd]))
- Part A, B and C: Number of Participants With Suicidal Ideation as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) Score(Baseline and post-baseline (up to 28 days))
- Part A: Change From Baseline in the Tremor Research Group (TRG) Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Total Score at Day 7(Baseline (Day 1) and Day 7 (8 hours postdose))
- Part A: Change From Baseline in TETRAS Performance Subscale Score (Items 6, 7, and 8) at Day 7(Baseline (Day 1) and Day 7 (predose))
- Part B: Change From Randomization in the Kinesia Upper Limb Total Score at Day 14(Randomization (Day 8, predose) and Day 14 (predose))
- Part B: Change From Randomization in the Kinesia Upper Limb Individual Item Score at Day 14(Randomization (Day 8, predose) and Day 14 (predose))
- Part C: Change From Baseline in the Kinesia Upper Limb Individual Item Score at Day 15(Baseline (Day 1) and Day 15)
- Part C: Change From Baseline in the TETRAS Upper Limb Total Score at Day 15(Baseline (Day 1) and Day 15)
- Part C: Change From Baseline in the TETRAS Upper Limb Individual Item (Performance Subscale Items 4a and 4b) Score at Day 15(Baseline (Day 1) and Day 15)
- Part C: Change From Baseline in TETRAS Performance Subscale (Items 6, 7, and 8) Scores at Day 15(Baseline (Day 1) and Day 15)
- Number of Participants With Clinically Significant Electrocardiogram (ECG) Values(Up to 28 days)
- Parts A, B and C: Change From Baseline in Bond-Lader Visual Analogue Scale (VAS) Score(Baseline (Day 1), Day 7 (predose) for Part A, Day 14 (predose) for Part B and Day 15 for Part C)
- Parts A, B and C: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) or Serious Adverse Event (SAE)(From first dose of study drug through 14 days after the last dose (Up to 28 days))
- Parts A, B and C: Participant's Feeling After Taking the Study Drug as Assessed by Drug Effects Questionnaire (DEQ-5) Score(Baseline (Day 1), Day 7 (2 hours postdose) for Part A, Day 14 (2 hours postdose) for Part B and Day 15 for Part C)