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A Clinical Trial of PRAX-944 in Participants With Essential Tremor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05021978
Recruitment Status : Completed
First Posted : August 26, 2021
Last Update Posted : May 27, 2022
Sponsor:
Collaborator:
Praxis Precision Medicines Australia Pty Ltd
Information provided by (Responsible Party):
Praxis Precision Medicines

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.

Condition or disease Intervention/treatment Phase
Essential Tremor Drug: Part A: 20 and 40 mg PRAX-944 Drug: Part B: 120 mg PRAX-944 Drug: Part B: 120 mg PRAX-944 and Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Part A: Single group Part B: Parallel group, randomized withdrawal
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Part A: Open label Part B: Open label titration followed by quadruple-blind, randomized withdrawal
Primary Purpose: Treatment
Official Title: A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults With Essential Tremor
Actual Study Start Date : March 3, 2020
Actual Primary Completion Date : March 24, 2022
Actual Study Completion Date : March 24, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Part A: 20 and 40 mg PRAX-944
Once daily oral treatment

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
Drug: Part B: 120 mg PRAX-944
Once daily oral treatment with titration

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
Drug: Part B: 120 mg PRAX-944 and Placebo
Once daily oral treatment with titration followed by placebo




Primary Outcome Measures :
  1. Part A: Change from baseline to Day 7 and Day 14 in the Essential Tremor Rating Assessment Scale (TETRAS) upper limb score [ Time Frame: 7 days, 14 days ]
    The TETRAS is a performance and activities of daily living (ADL) 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. The TETRAS upper limb score is item 4 of the TETRAS PS. This item is rated on a 5-point scale (ranging from 0 to 4). This item 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 item ranges from 0 to 24 with higher scores indicating greater tremor severity.

  2. Part B: Incidence and severity of Adverse Events (AE) [ Time Frame: 56 days ]
    An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study drug, whether or not considered related to the study drug.

  3. Part B: Incidence of AEs by preferred term [ Time Frame: 56 days ]
    The incidence of AEs will be reported by preferred term, including any terms related to clinically significant changes in 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), and Columbia-Suicide Severity Rating Scale (C-SSRS) responses.


Secondary Outcome Measures :
  1. Part A: Change from baseline to Day 7 and Day 14 on the Essential Tremor Rating Assessment Scale (TETRAS) Performance subscale [ Time Frame: 7 days, 14 days ]
    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.

  2. Part A: Change from baseline to Day 7 and Day 14 in the Essential Tremor Rating Assessment Scale (TETRAS) upper limb score measured by accelerometry [ Time Frame: 7 days, 14 days ]
    The TETRAS is an essential tremor and activities of daily living (ADL) 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. The TETRAS upper limb score is item 4 of the upper limb body region. This item is rated on a 5-point scale (ranging from 0 to 4). This item 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 item ranges from 0 to 24 with higher scores indicating greater tremor severity. This outcome will be measured by accelerometry with measurements of rotations and accelerations in 3D space over time converted into ratings according to the scale outlined above.

  3. Part A: Incidence of AEs by preferred term [ Time Frame: 14 days ]
    The incidence of AEs will be reported by preferred term, including any terms related to clinically significant changes in 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), and Columbia-Suicide Severity Rating Scale (C-SSRS) responses.

  4. Part A: Incidence and severity of Adverse Events (AE) [ Time Frame: 14 days ]
    An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of study drug, whether or not considered related to the study drug.

  5. Part B: Change from baseline to Day 42 in the Essential Tremor Rating Assessment Scale (TETRAS) upper limb score [ Time Frame: 42 days ]
    The TETRAS is an essential tremor and activities of daily living (ADL) 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. The TETRAS upper limb score is item 4 of the upper limb body region. This item is rated on a 5-point scale (ranging from 0 to 4). This item 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 item ranges from 0 to 24 with higher scores indicating greater tremor severity.

  6. Part B: Change from baseline to Day 7 and Day 21 in the Essential Tremor Rating Assessment Scale (TETRAS) upper limb score [ Time Frame: 7 days, 21 days ]
    The TETRAS is an essential tremor and activities of daily living (ADL) 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. The TETRAS upper limb score is item 4 of the upper limb body region. This item is rated on a 5-point scale (ranging from 0 to 4). This item 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 item ranges from 0 to 24 with higher scores indicating greater tremor severity.

  7. Part B: Change from baseline to Day 7, Day 21, and Day 42 on the Essential Tremor Rating Assessment Scale (TETRAS) Performance subscale [ Time Frame: 7 days, 21 days, 42 days ]
    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.

  8. Part B: Change from baseline to Day 7, Day 21, and Day 42 in the Essential Tremor Rating Assessment Scale (TETRAS) upper limb score measured by accelerometry [ Time Frame: 7 days, 21 days, 42 days ]
    The TETRAS is an essential tremor and activities of daily living (ADL) 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. The TETRAS upper limb score is item 4 of the upper limb body region. This item is rated on a 5-point scale (ranging from 0 to 4). This item 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 item ranges from 0 to 24 with higher scores indicating greater tremor severity. This outcome will be measured by accelerometry with measurements of rotations and accelerations in 3D space over time converted into ratings according to the scale outlined above.

  9. Part B: Change from baseline to Day 7, Day 21, and Day 42 on the TETRAS Activities of Daily Living (ADL) score [ Time Frame: 7 days, 21 days, 42 days ]
    The TETRAS is an essential tremor and ADL rating scale. The full scale has 2 sections, the Performance subscale and the ADL subscale. The ADL subscale consists of 12 items measuring the impact of essential tremor on typical daily activities. These 12 items are rated on a 5-point scale (ranging from 0 to 4). The total score of the 12 items ranges from 0 to 60 with higher scores indicating greater tremor severity.

  10. Part B: Change from baseline to Day 7, Day 21, and Day 42 on the Quality of Life in Essential Tremor Questionnaire (QUEST) total and subscale scores. [ Time Frame: 7 days, 21 days, 42 days ]
    The QUEST is a brief, 30-item, patient-reported ET-specific quality of life scale. The scale contains 5 subscales that cover physical, psychosocial, communication, hobbies/leisure, and work/finance dimensions. The individual items are rated either on a 5-level Likert scale from 0 to 4 (never, rarely, sometimes, frequently, always) or a 2-level scale from 0 (no) to 4 (yes) relative to the respondent's current situation. Five items could also be rated as not applicable. Respondents are also asked to indicate which tremor was perceived to impact a function or be associated with the feeling or attitude in question. 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 scores indicate greater impact of tremor on quality of life.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05021978


Locations
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United States, Florida
Praxis Research Site
Port Charlotte, Florida, United States, 33980
United States, Washington
Praxis Research Site
Spokane, Washington, United States, 99202
Australia, New South Whales
Praxis Research Site
New Lambton Heights, New South Whales, Australia, 2305
Australia, Queensland
Praxis Research Site
Southport, Queensland, Australia, 4215
Australia, Victoria
Praxis Research Site
Fitzroy, Victoria, Australia, 3065
Praxis Research Site
Melbourne, Victoria, Australia, 3004
Praxis Research Site
Parkville, Victoria, Australia, 3050
New Zealand
Praxis Research Site
Grafton, Auckland, New Zealand, 1023
Praxis Research Site
Christchurch, New Zealand, 8011
Sponsors and Collaborators
Praxis Precision Medicines
Praxis Precision Medicines Australia Pty Ltd
Investigators
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Study Director: VP, Clinical Development Praxis Precision Medicines
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Responsible Party: Praxis Precision Medicines
ClinicalTrials.gov Identifier: NCT05021978    
Other Study ID Numbers: PRAX-944-221
First Posted: August 26, 2021    Key Record Dates
Last Update Posted: May 27, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Praxis Precision Medicines:
Movement Disorder
Benign Essential Tremor
Familial Tremor
Hereditary Essential Tremor
Movement Disorder Agents
Calcium Channels, T-type
Additional relevant MeSH terms:
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Tremor
Essential Tremor
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Movement Disorders
Central Nervous System Diseases
Pramoxine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents