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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05021978
Registration number
NCT05021978
Ethics application status
Date submitted
20/08/2021
Date registered
26/08/2021
Date last updated
1/03/2024
Titles & IDs
Public title
A Clinical Trial of PRAX-944 in Participants With Essential Tremor
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Scientific title
A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults With Essential Tremor
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Secondary ID [1]
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PRAX-944-221
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Essential Tremor
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Condition category
Condition code
Neurological
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Other neurological disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Part A: 20 and 40 mg PRAX-944
Treatment: Drugs - Part B: 120 mg PRAX-944
Treatment: Drugs - Part B: 120 mg PRAX-944 and Placebo
Experimental: Part A: Open-label 20 and 40 mg PRAX-944 - Once daily, oral dosing with 7 days of 20 mg and 7 days of 40 mg
Experimental: Part B: Open-label titration PRAX-944 (120 mg) followed by blinded PRAX-944 - Once daily, oral dosing with titration to 120 mg: 3 days of 20 mg, 4 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 7 days of 100 mg, 28 days of 120 mg
Active Comparator: Part B: Open-label titration PRAX-944 (120 mg) followed by blinded placebo - Once daily, oral dosing with titration to 120 mg: 3 days of 20 mg, 4 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 7 days of 100 mg, 14 days of 120 mg, 14 days placebo
Treatment: Drugs: Part A: 20 and 40 mg PRAX-944
Once daily oral treatment
Treatment: Drugs: Part B: 120 mg PRAX-944
Once daily oral treatment with titration
Treatment: Drugs: Part B: 120 mg PRAX-944 and Placebo
Once daily oral treatment with titration followed by placebo
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline (Day 0), Days 7 and 14
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Primary outcome [2]
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Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
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Assessment method [2]
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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.
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Timepoint [2]
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Up to Day 70
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Primary outcome [3]
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Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
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Assessment method [3]
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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.
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Timepoint [3]
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Up to Day 70
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Primary outcome [4]
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Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
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Assessment method [4]
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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).
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Timepoint [4]
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Up to Day 70
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Secondary outcome [1]
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Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale
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Assessment method [1]
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The TETRAS is an essential tremor and activities of daily living rating scale. The full scale has 2 sections, the Performance subscale (PS) and the ADL subscale. The PS consists of 9 items covering different body regions. These 9 items are rated on a 5-point scale (ranging from 0 to 4). One item, Item 4, consists of ratings for 3 tasks rated separately for upper limbs on both sides of the body for a total of 6 ratings. The total score of the 9 items (14 ratings) ranges from 0 to 70 with higher scores indicating greater tremor severity. The total score and individual item ratings will be evaluated as outcomes in this trial. Baseline is defined as the last non-missing value collected prior to receiving first dose of study drug.
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Timepoint [1]
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Baseline (Day 0), Days 7 and 14
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Secondary outcome [2]
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Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry
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Assessment method [2]
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Accelerometer was used to evaluate record coordinates and accelerations in the 3D space over time. The 3 maneuvers in the upper limb item will be completed for both arms, first for the right arm and then for the left. Each upper limb sub-item is scored on a scale from 0 to 4 including to 0.1 increments. The accelerometer upper limb total score, ranges from 0 to 24. A decrease in score is indicative of improvement. 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.
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Timepoint [2]
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Baseline (Day 0), Days 7 and 14
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Secondary outcome [3]
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Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)
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Assessment method [3]
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The TETRAS ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 with higher scores reflecting higher impact. 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.
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Timepoint [3]
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Baseline (Day 0), Days 7 and 14
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Secondary outcome [4]
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Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation
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Assessment method [4]
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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.
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Timepoint [4]
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Up to Day 21
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Secondary outcome [5]
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Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters
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Assessment method [5]
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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.
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Timepoint [5]
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Up to Day 21
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Secondary outcome [6]
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Part A: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS)
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Assessment method [6]
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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).
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Timepoint [6]
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Up to Day 21
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Secondary outcome [7]
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Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline (Day 0) and Day 42
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Secondary outcome [8]
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Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase
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Assessment method [8]
0
0
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.
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Timepoint [8]
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Baseline (Day 0), Days 7 and 21
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Secondary outcome [9]
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Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase
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Assessment method [9]
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TETRAS Performance Subscale was used to assess essential tremor as scored by the independent video raters. The performance subscale consists of 9 items, i.e. item 1 (head), item 2 (face), item 3 (voice), each of the 6 sub-items for item 4 (upper limb), the maximum of the 4 sub-items for item 5 (lower limb), 2 sub-items (right and left side) for item 6 (Archimedes spirals), item 7 (handwriting), 2 sub-items (right and left side) for item 8 (dot approximation), and item 9 (standing) for a total score ranging from 0 to 64 from 16 sub-items. Each item is rated on a scale of 0 to 4, including 0.5 increments. A lower score is indicative of improvement. The total score has been presented. 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.
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Timepoint [9]
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Baseline (Day 0) and Days 7, 21 and 42
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Secondary outcome [10]
0
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Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase
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Assessment method [10]
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Accelerometer was used to evaluate record coordinates and accelerations in the 3D space over time. The 3 maneuvers in the upper limb item will be completed for both arms, first for the right arm and then for the left. Each upper limb sub-item is scored on a scale from 0 to 4 including to 0.1 increments. The accelerometer upper limb total score, ranges from 0 to 24. A decrease in score is indicative of improvement. 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.
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Timepoint [10]
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Baseline (Day 0), and Days 7, 21 and 42
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Secondary outcome [11]
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Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting)
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Assessment method [11]
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TETRAS Performance Subscale was used to assess essential tremor as scored by the independent video raters. The performance subscale consists of 9 items, i.e. item 1 (head), item 2 (face), item 3 (voice), each of the 6 sub-items for item 4 (upper limb), the maximum of the 4 sub-items for item 5 (lower limb), 2 sub-items (right and left side) for item 6 (Archimedes spirals), item 7 (handwriting), 2 sub-items (right and left side) for item 8 (dot approximation), and item 9 (standing) for a total score ranging from 0 to 64 from 16 sub-items. Each item is rated on a scale of 0 to 4, including 0.5 increments. A lower score is indicative of improvement. 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.
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Timepoint [11]
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Baseline (Day 0), Days 7, 21 and 42
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Secondary outcome [12]
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Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score
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Assessment method [12]
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The TETRAS ADL subscale is a 12-item assessment of typical daily activities that are impacted by tremor. Activities are assessed in the following functional domains: speaking, feeding, drinking, personal hygiene, dressing, writing, and social activity. The impact to each function is rated on a 5-point Likert scale from 0 to 4. The ADL subscale score is calculated as the sum of all 12 items and ranges from 0 to 48 with higher scores reflecting higher impact. 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.
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Timepoint [12]
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Baseline (Day 0), Days 7, 21 and 42
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Secondary outcome [13]
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Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores.
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Assessment method [13]
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Quality of Life in Essential Tremor Questionnaire (QUEST) is a patient-reported ET-specific 30-item, specific quality of life scale. Items contribute to five dimensions. Physical/ADL (9 items ), Psychosocial (9 items), Communication (3 items), Hobbies/Leisure (3 items), and Work/Finances (6 items). The QUEST total and subscale scores are calculated as the sum of all applicable items divided by the number of applicable items times 100. Higher score indicates greater dissatisfaction with that domain of QOL. Maximal score 100: worse quality of life. Minimal Score 0: best quality of life. 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.
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Timepoint [13]
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Baseline (Day 0), Days 7, 21 and 42
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Eligibility
Key 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).
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/03/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
24/03/2022
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Sample size
Target
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Accrual to date
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Final
24
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Recruitment in Australia
Recruitment state(s)
New South WhalesQLD,VIC
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Recruitment hospital [1]
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Praxis Research Site - New Lambton Heights
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Recruitment hospital [2]
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Praxis Research Site - Southport
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Recruitment hospital [3]
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Praxis Research Site - Fitzroy
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Recruitment hospital [4]
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Praxis Research Site - Melbourne
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Recruitment hospital [5]
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Praxis Research Site - Parkville
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Recruitment postcode(s) [1]
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2305 - New Lambton Heights
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Recruitment postcode(s) [2]
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4215 - Southport
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Recruitment postcode(s) [3]
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3065 - Fitzroy
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Recruitment postcode(s) [4]
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3004 - Melbourne
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Recruitment postcode(s) [5]
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3050 - Parkville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Florida
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Country [2]
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United States of America
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State/province [2]
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Washington
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Country [3]
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New Zealand
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State/province [3]
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Auckland
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Country [4]
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0
New Zealand
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State/province [4]
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Christchurch
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Praxis Precision Medicines
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Address
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Country
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05021978
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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VP, Clinical Development
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Address
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Praxis Precision Medicines
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Country
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Phone
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Fax
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Email
0
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05021978
Download to PDF