| Primary | Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score | 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. | Full Analysis Set (FAS): all participants who took at least 1 dose of study drug and had a valid baseline TETRAS assessment and at least 1 valid post-baseline TETRAS assessment. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | Scores on a scale | | Baseline (Day 0), Days 7 and 14 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
| | | Title | Denominators | Categories |
|---|
| Change from baseline to Day 7 | | | Title | Measurements |
|---|
| - OG000-1.427(-4.4375 to 1.5845)
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| | Change from baseline to Day 14 | | | Title | Measurements |
|---|
| - OG000-2.912(-4.2779 to -1.5466)
|
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| Sample size is a convenience sample determined according to feasibility to provide sufficient and safety data to inform the development of future controlled studies with PRAX-944. In the open-label phase of the trial (Part A ), at least 10 participants would provide an 80% probability of observing at least 1 AE with an underlying incidence of 15% or greater and provide approximately 80% power to detect an effect size of 1.0 on the primary endpoint change from baseline in TETRAS Upper Limb score. | Mixed Models Analysis | Includes timepoint as fixed effect and baseline TETRAS score as a covariate. Within subject variability modeled using unstructured covariance pattern. | 0.1048 | Change from baseline to Day 7 in TETRAS Upper Limb Score | | | | | | | | | | | |
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| Primary | Part B: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation | 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. | Safety Analysis Set included all participants who received at least 1 dose of study drug. | Posted | | Number | | participants | | Up to Day 70 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks | | OG001 | Part B: PRAX-944 120mg RWD | Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days. | | OG002 | Part B: Placebo RWD | Participants in double-blind, randomized withdrawal phase were administered Placebo for 14 days. |
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| Primary | Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters | 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. | | Posted | | Number | | participants | | Up to Day 70 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks | | OG001 | Part B: PRAX-944 120mg RWD | Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days. | | OG002 | Part B: Placebo RWD |
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| Primary | Part B: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | 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). | | Posted | | Number | | Participants | | Up to Day 70 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks | | OG001 | Part B: PRAX-944 120mg RWD | Participants in double-blind, randomized withdrawal phase were administered PRAX-944 120mg for 14 days. |
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| Secondary | Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale | 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. | FAS population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7 and 14 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
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| Secondary | Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry | 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. | FAS Population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7 and 14 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
| |
| Secondary | Part A: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) | 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. | FAS population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7 and 14 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
| |
| Secondary | Part A: Number of Participants With Adverse Events (AE), Related AE, and AE Leading to Treatment Discontinuation | 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. | | Posted | | Number | | participants | | Up to Day 21 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
| |
| Secondary | Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Values and Electrocardiogram Parameters | 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. | | Posted | | Number | | Participants | | Up to Day 21 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
| |
| Secondary | Part A: Number of Participants With Suicidal Ideation or Behavior Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) | 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). | | Posted | | Number | | Participants | | Up to Day 21 | | | | ID | Title | Description |
|---|
| OG000 | Part A: PRAX-944 20mg to 40mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg (7 days) to 40 mg (7 days). |
| |
| Secondary | Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase | 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. | FAS Population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0) and Day 42 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |
| Secondary | Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score During OLT Phase | 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. | FAS. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7 and 21 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |
| Secondary | Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale During OLT Phase | 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. | FAS population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0) and Days 7, 21 and 42 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |
| Secondary | Part B: Change From Baseline in Essential Tremor Rating Assessment Scale (TETRAS) Upper Limb Score Measured by Accelerometry During OLT Phase | 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. | FAS population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), and Days 7, 21 and 42 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |
| Secondary | Part B: Change From Baseline in TETRAS Performance Subscale Individual Items # 6 (Spiral Drawing) and Items #7 (Handwriting) | 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. | FAS Population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7, 21 and 42 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |
| Secondary | Part B: Change From Baseline in TETRAS Activities of Daily Living (ADL) Score | 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. | FAS population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7, 21 and 42 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |
| Secondary | Part B: Change From Baseline in Quality of Life in Essential Tremor Questionnaire (QUEST) Total Scores. | 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. | FAS population. Only those participants with data available at indicated timepoints have been presented. | Posted | | Least Squares Mean | 95% Confidence Interval | scores on a scale | | Baseline (Day 0), Days 7, 21 and 42 | | | | ID | Title | Description |
|---|
| OG000 | Part B: PRAX-944 20mg to 120mg OLT | Participants in open-label titration phase were administered once daily oral dose of PRAX-944 titrated from 20 mg to up to 120 mg for 6-weeks. |
| |