Clinical trial NCT05021978: A Clinical Trial of PRAX-944 in Participants With Essential Tremor
Official title: A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults With Essential Tremor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor
Keywords: Movement Disorder
Benign Essential Tremor
Familial Tremor
Hereditary Essential Tremor
Movement Disorder Agents
Calcium Channels, T-type
Lead sponsor: Praxis Precision Medicines
Sponsor class: INDUSTRY
First posted: 2021-08-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A: Single group Part B: Parallel group, randomized withdrawal
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. 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
3. 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 1.
4. Body mass index (BMI) between 18 and 40 kg/m2 (inclusive).

Exclusion Criteria:

1. Sporadically using a benzodiazepine, sleep medication, or anxiolytic that would confound the assessment of tremor.
2. Trauma to the nervous system within 3 months preceding the onset of tremor.
3. 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.
4. Prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
5. Botulinum toxin injection for ET in the 6 months prior to Screening.
6. Unwilling or unable to refrain from alcohol 24 hours before and during clinical trial visits.
7. History of substance use disorder

Primary outcomes:
measure: Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score
timeFrame: Baseline (Day 0), Days 7 and 14
measure: Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
timeFrame: Up to Day 70
measure: Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
timeFrame: Up to Day 70
measure: Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Day 70
Secondary outcomes:
measure: Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale
timeFrame: Baseline (Day 0), Days 7 and 14
measure: Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry
timeFrame: Baseline (Day 0), Days 7 and 14
measure: Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)
timeFrame: Baseline (Day 0), Days 7 and 14
measure: Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
timeFrame: Up to Day 21
measure: Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
timeFrame: Up to Day 21
measure: Part A: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Day 21
measure: Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase
timeFrame: Baseline (Day 0) and Day 42
measure: Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase
timeFrame: Baseline (Day 0), Days 7 and 21
measure: Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase
timeFrame: Baseline (Day 0) and Days 7, 21 and 42
measure: Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase
timeFrame: Baseline (Day 0), and Days 7, 21 and 42
measure: Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)
timeFrame: Baseline (Day 0), Days 7, 21 and 42
measure: Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score
timeFrame: Baseline (Day 0), Days 7, 21 and 42
measure: Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores.
timeFrame: Baseline (Day 0), Days 7, 21 and 42
Other outcomes:
Locations:
city: Port Charlotte
country: United States
facility: Praxis Research Site
state: Florida
city: Spokane
country: United States
facility: Praxis Research Site
state: Washington
city: New Lambton Heights
country: Australia
facility: Praxis Research Site
state: New South Whales
city: Southport
country: Australia
facility: Praxis Research Site
state: Queensland
city: Fitzroy
country: Australia
facility: Praxis Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Praxis Research Site
state: Victoria
city: Parkville
country: Australia
facility: Praxis Research Site
state: Victoria
city: Grafton
country: New Zealand
facility: Praxis Research Site
state: Auckland
city: Christchurch
country: New Zealand
facility: Praxis Research Site
Study officials:
affiliation: Praxis Precision Medicines
name: VP, Clinical Development
role: STUDY_DIRECTOR
References: