A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Response Study of SAGE-324 for the Treatment of Essential Tremor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 146
- 试验地点
- 1
- 主要终点
- Change From Baseline in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Total Score on Day 91 in the Monotherapy Cohort
研究概览
简要总结
The primary purpose of this study is to evaluate the dose-response relationship of different doses of SAGE-324 on upper extremity tremor in participants with essential tremor (ET) in the monotherapy cohort.
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
- •Diagnosis of ET, as defined by all of the following criteria:
- •Isolated tremor syndrome consisting of bilateral upper limb action tremor
- •At least 3 years duration
- •With or without tremor in other locations (eg, head, voice, or lower limbs)
- •Absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (eg, voice, head), task- and position-specific tremors, sudden tremor onset, or evidence of stepwise deterioration of tremor.
- •Participant has the following:
- •Scores of at least 12 in the combined TETRAS Performance Subscale Item 4 (upper limb tremor) at both Screening and pre-dose on Day 1
- •Scores of at least 6 in the total TETRAS Performance Subscale Item 4 score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) at both Screening and pre-dose on Day 1
- •Participant has a baseline TETRAS ADL Subscale score of at least 20 at Screening.
- •Willing to discontinue medications taken for the treatment of ET except propranolol at least 14 days or 5 half-lives (whichever is longer) prior to receiving the investigational product (IP). Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day
- •Participants in the adjunct therapy cohort must be on a stable dose of propranolol (maximum total daily propranolol dose up to 320 mg allowed) for the treatment of ET from 3 months prior to Screening through Day 97 of the study.
- •Participant is willing to limit use of alcohol to 2 units per day for males and 1 unit per day for females starting at least 1 week prior to Day 1 and through Day 97 of the study.
- •Participant is willing to maintain prestudy consumption of products that contain nicotine starting at least 1 week prior to Day 1 and through Day 97 of the study.
排除标准
- •Presence of known causes of enhanced physiological tremor.
- •Participant has had newly administered tremorgenic drugs (14 days or 5 half-lives [whichever is longer] prior to Day 1) or presence of alcohol withdrawal state.
- •Direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
- •Previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR) guided procedure, eg, MR-guided focused ultrasound. Use of Cala Trio bracelet for the treatment of ET from two weeks prior to Day 1 through Day 97 is prohibited.
- •Participant has had botulinum toxin for treatment of ET within 6 months of Screening.
- •Historical or clinical evidence of tremor with functional neurological syndrome origin.
- •Participant currently requires propranolol treatment for a medical condition other than ET.
- •Participant has history of substance abuse or dependence prior to Screening, has a positive screen for drugs of abuse at Screening or predose on Day
- •Participants with nicotine use disorder that impacts their tremor are excluded.
研究组 & 干预措施
SAGE-324 Matched Placebo
Participants will receive SAGE-324 matched placebo, stratified by baseline propranolol use.
Monotherapy:
Participants will receive SAGE-324 matched placebo, oral tablets, once daily (QD), in the evening, from Day 1 to Day 90 in a double-blind treatment period.
Adjunct therapy:
Participants will receive SAGE-324 matched placebo, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 milligrams (mg) of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.
干预措施: SAGE-324 Matched Placebo (Drug)
SAGE-324 15 mg
Participants will receive SAGE-324, 15 mg, stratified by baseline propranolol use.
Monotherapy:
Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
Adjunct therapy:
Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.
干预措施: SAGE-324 (Drug)
SAGE-324 30 mg
Participants will receive SAGE-324, 30 mg, stratified by baseline propranolol use.
Monotherapy:
Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
Adjunct therapy:
Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.
干预措施: SAGE-324 (Drug)
SAGE-324 60 mg
Participants will receive SAGE-324: 15 mg, 30 mg, 45 mg, and 60 mg, stratified by baseline propranolol use.
Monotherapy:
Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
Adjunct therapy:
Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.
干预措施: SAGE-324 (Drug)
结局指标
主要结局
Change From Baseline in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Total Score on Day 91 in the Monotherapy Cohort
时间窗: Baseline, Day 91
TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. For the TETRAS Performance Subscale Item 4 (upper limb), three maneuvers/assessments were to be completed for both arms, first for the right arm and then for the left, specifically Item 4a, limbs extended forward maneuver (postural tremor), Item 4b, wing-beating \[elbows flexed\] maneuver (postural tremor), and Item 4c finger-nose-finger maneuver (kinetic tremor). Each assessment is rated on a 0 to 4 scale of severity in 0.5-point increments, with higher scores indicating more severe tremor. The Performance Subscale Item 4 (upper limb) total score range for a given side (left or right) is 0 to 12, and for both sides combined is 0 to 24. A negative change from baseline indicates improvement. Mixed model for repeated measures (MMRM) was used for the analysis.
次要结局
- Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort(Baseline, Day 91)