A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults With Essential Tremor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 10
- 主要终点
- Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score
研究概览
简要总结
This is a 2-part clinical trial to evaluate the efficacy, safety, and tolerability of 40 and 120 mg oral PRAX-944 compared to placebo in the treatment of adults with essential tremor. Part A is designed to study the dose titration from 20 to 40 mg every morning (QAM) (ie, 2 weeks with 7 days at each dose level). Part B is designed to study the dose titration from 20 to up to 120 mg QAM with at least 14 days of dosing at the highest tolerated dose for each participant. Blood levels of PRAX-944 will also be measured throughout the trial and pharmacokinetics will be evaluated.
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)
盲法说明
Part A: Open label Part B: Open label titration followed by quadruple-blind, randomized withdrawal
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
- •Clinical diagnosis of ET consistent with Movement Disorders Society Criteria, a duration of ET of at least 3 years and with onset before the age of 65
- •TETRAS upper limb score (ie, sum of bilateral upper limb items 4a, 4b, and 4c) of ≥10 as rated by the Investigator at Screening and Baseline OR A score of ≥2 on 2 or more of the following TETRAS activities of daily living (ADL) subscale items: (2) Feeding with a spoon, (3) Drinking from a glass, (5) Dressing, (6) Pouring, (9) Writing OR A score of ≥2 on 1 of the following TETRAS ADL subscale items: (2) Feeding with a spoon, (3) Drinking from a glass, (5) Dressing, (6) Pouring, or (9) Writing AND a score of ≥2 on both of the following TETRAS ADL subscale items: (10) Working and (12) Social Impact
- •If currently receiving any medication for ET, is on a stable dose of any of these medications for ET for 28 days prior to Screening and is willing to maintain stable doses throughout the trial. If receiving primidone for ET, is willing and able to discontinue 14 days prior to Day
- •Body mass index (BMI) between 18 and 40 kg/m2 (inclusive).
排除标准
- •Sporadically using a benzodiazepine, sleep medication, or anxiolytic that would confound the assessment of tremor.
- •Trauma to the nervous system within 3 months preceding the onset of tremor.
- •History of other medical, neurological or psychiatric condition that may explain or cause tremor, including but not limited to Parkinson's disease, dystonia, cerebellar disease, family history of Fragile X syndrome, traumatic brain injury, alcohol abuse or withdrawal, benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism.
- •Prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
- •Botulinum toxin injection for ET in the 6 months prior to Screening.
- •Unwilling or unable to refrain from alcohol 24 hours before and during clinical trial visits.
- •History of substance use disorder
结局指标
主要结局
Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score
时间窗: Baseline (Day 0), Days 7 and 14
The TETRAS upper limb score is calculated as the sum of the 6 separate upper-limb maneuvers assessed by the clinician: forward-outstretched postural tremor \[right\], forward outstretched postural tremor \[left\], lateral wing-beating postural tremor \[right\], lateral wing-beating postural tremor \[left\], kinetic tremor \[right\], kinetic tremor \[left\], each on a 0 (no tremor) to 4 (maximum tremor) severity scale in 0.5-point increments. TETRAS Part 4 score for both upper limbs ranged from 0 to 24, higher scores indicated more severe tremor. A negative change from baseline indicated less tremor. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug. Change from baseline will be defined as assessment value minus baseline value.
Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
时间窗: Up to Day 70
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Incidence and Severity of Adverse Events have been reported.
Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
时间窗: Up to Day 70
Vital signs parameters included body temperature, pulse rate, respiratory rate, blood pressure (systolic and diastolic), clinical laboratory measures (chemistry, hematology, urinalysis, and coagulation), electrocardiogram parameters (heart rate, PR, QRS, QT, and corrected QT intervals). Any change in vital sign abnormalities that was clinically significant in the medical and scientific judgment of the investigator and not related to an underlying disease was reported as an unsolicited adverse event (AE). Any clinically significant abnormality associated with underlying disease does not require reporting as an (S)AE unless judged by the investigator to be more severe than expected for the participant's condition.
Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to Day 70
The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. Four constructs were measured. Severity of Suicidal ideation is rated on a 5-point ordinal scale. Intensity of ideation is comprised of 5 items (frequency, duration, controllability, deterrents, and reason for ideation), each rated on a 5-point ordinal scale. Suicidal behavior is rated on a nominal scale that includes actual, aborted, and interrupted attempts; preparatory behavior; and non-suicidal self-injurious behavior. Lethality, assesses actual attempts; actual lethality is rated on a 6-point ordinal scale, and if actual lethality is 0, potential lethality of attempts is rated on a 3-point ordinal scale.The higher the C-SSRS score, the higher the suicide risk (ie. worse outcome).
次要结局
- Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score(Baseline (Day 0), Days 7, 21 and 42)
- Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters(Up to Day 21)
- Part A: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)(Up to Day 21)
- Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase(Baseline (Day 0) and Days 7, 21 and 42)
- Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores.(Baseline (Day 0), Days 7, 21 and 42)
- Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale(Baseline (Day 0), Days 7 and 14)
- Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry(Baseline (Day 0), Days 7 and 14)
- Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)(Baseline (Day 0), Days 7 and 14)
- Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase(Baseline (Day 0), Days 7 and 21)
- Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase(Baseline (Day 0), and Days 7, 21 and 42)
- Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation(Up to Day 21)
- Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)(Baseline (Day 0), Days 7, 21 and 42)