A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor

Essential Tremor Clinical Trial

— Essential1  

Official title:

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of PRAX-944 in the Treatment of Adults With Essential Tremor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05021991
• Other study ID #: PRAX-944-222
• Status: Completed
• Phase: Phase 2
• Start date: October 14, 2021
• Est. completion date: February 29, 2024

Study information

• Verified date: March 2024
• Source: Praxis Precision Medicines
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This multi-center, randomized, double-blinded, placebo-controlled, dose-range-finding clinical trial (with an optional Extension comprised of an Extension Double-blind (DB) Lead in Period followed by an Extension Open-label (OL) Period) that will assess the efficacy, safety, and tolerability of PRAX 944 in participants aged 18 years or older who have a diagnosis of Essential Tremor (ET) and have had symptoms for at least 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: February 29, 2024
• Est. primary completion date: February 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Clinical diagnosis of ET, including: (a) tremor syndrome of bilateral upper limb action tremor, (b) at least 3 years in duration, (c) with or without tremor in other locations (eg, head, voice, or lower limbs), (d) If the symptoms and signs are judged by the investigator to be due to the diagnosis of ET, it is acceptable for them to also have one or more of the following ET plus signs: (i) mild dystonic posturing, (ii) mild rest tremor in the setting of advanced ET and in the absence of other features of Parkinsonism, (iii) intention tremor, (iv) mild increase in tandem gait difficulty.

2. Participant has moderate to severe functional impairment due to tremor as determined by the TETRAS and CGI-S.

3. If currently receiving any medication for ET, is on a stable dose of any of these medications for ET for 1 month 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 or clinical evidence of other medical, neurological, or psychiatric condition that may explain or cause tremor, including but not limited to Parkinson's disease, Huntington's disease, Alzheimer's disease, cerebellar disease (including spinocerebellar ataxias), primary dystonia, Fragile X Tremor/Ataxia syndrome or family history of Fragile X syndrome, traumatic brain injury, psychogenic tremor, alcohol or benzodiazepine abuse or withdrawal, multiple sclerosis, polyneuropathy, and endocrine states such as hyperthyroidism or unstable treatment of hypothyroidism or medication, food, or supplement induced movement disorders (eg, tremor related to beta agonists or caffeine), or other medical, neurological, or psychiatric conditions that may explain or cause tremor

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 Baseline.

6. Cala trio health device for ET in the 14 days prior to Baseline and throughout the study.

7. History of substance use disorder consistent with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Participants with a previous diagnosis of substance use disorder who have been in remission for at least 2 years can participate in the trial.

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Drug:
• 100 mg PRAX-944
Once daily oral treatment with titration
• 60 mg PRAX-944
Once daily oral treatment with titration
• Placebo
Once daily oral treatment
• Flexibly dosed 20 mg to 100 mg PRAX-944
Once daily oral treatment

Locations

Country	Name	City	State
Canada	Praxis Research Site	Halifax	Nova Scotia
Canada	Praxis Research Site	Montréal	Quebec
Canada	Praxis Research Site	Toronto	Ontario
Canada	Praxis Research Site	Vancouver	British Columbia
United States	Praxis Research Site	Alexandria	Virginia
United States	Praxis Research Site	Aurora	Colorado
United States	Praxis Research Site	Birmingham	Alabama
United States	Praxis Research Site	Boca Raton	Florida
United States	Praxis Research Site	Boston	Massachusetts
United States	Praxis Research Site	Burlington	Massachusetts
United States	Praxis Research Site	Burlington	Vermont
United States	Praxis Research Site	Chicago	Illinois
United States	Praxis Research Site	Cincinnati	Ohio
United States	Praxis Research Site	Farmington Hills	Michigan
United States	Praxis Research Site	Gainesville	Florida
United States	Praxis Research Site	Georgetown	Texas
United States	Praxis Research Site	Golden Valley	Minnesota
United States	Praxis Research Site	Houston	Texas
United States	Praxis Research Site	Jacksonville	Florida
United States	Praxis Research Site	Kansas City	Kansas
United States	Praxis Research Site	Kirkland	Washington
United States	Praxis Research Site	Las Vegas	Nevada
United States	Praxis Research Site	Little Rock	Arkansas
United States	Praxis Research Site	Louisville	Kentucky
United States	Praxis Research Site	Milwaukee	Wisconsin
United States	Praxis Research Site	New York	New York
United States	Praxis Research Site	New York	New York
United States	Praxis Research Site	Philadelphia	Pennsylvania
United States	Praxis Research Site	Port Charlotte	Florida
United States	Praxis Research Site	Rockville	Maryland
United States	Praxis Research Site	Round Rock	Texas
United States	Praxis Research Site	Saint Petersburg	Florida
United States	Praxis Research Site	San Diego	California
United States	Praxis Research Site	Santa Monica	California
United States	Praxis Research Site	Spokane	Washington
United States	Praxis Research Site	Tampa	Florida
United States	Praxis Research Site	Torrance	California
United States	Praxis Research Site	Virginia Beach	Virginia
United States	Praxis Research Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Praxis Precision Medicines

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to Day 56 on the modified ADL	The modified ADL is a composite sum of items 1 to 11 of the TETRAS-ADL subscale and items 6 and 7 on the TETRAS-PS. The impact to each function is rated on a 5-point Likert scale from 0 to 4. Before calculating the total score, a scoring adjustment is applied to each item score. The modified ADL score is calculated as the sum of all 13 items (with scoring adjustments) and ranges from 0 to 42 where larger values represent increased direct tremor impact to activities of daily living.	56 days
Secondary	Change from baseline to Day 56 on the Clinical Global Impression-Severity (CGI-S)	The CGI-S assesses the clinician's impression of the participant's current illness state. The clinician should use his/her total clinical experience with this patient population and rate the current severity of the participant's ET on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).	56 days
Secondary	Clinical Global Impression-Improvement (CGI-I) score at Day 56	The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to pre-treatment on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement/worsening is drug-related or not.	56 days
Secondary	Change from baseline to Day 56 on the TETRAS-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 where larger values represent increased direct tremor impact to activities of daily living.	56 days
Secondary	Change from baseline to Day 56 on the TETRAS-Performance Subscale (PS) total score	There are 9 items covering different body regions in the Performance Subscale. Each Performance Subscale item is rated on a scale of 0 to 4, with higher scores indicating higher tremor severity. Item 4 of the Performance Subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). The Performance subscale score is calculated as the sum of all 9 items and ranges from 0 to 64 where larger values represent higher tremor severity.	56 days
Secondary	Change from baseline to Day 56 on the TETRAS-upper limb (UL) score (TETRAS-PS item 4)	Item 4 of the Performance subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). Each sub-item is rated on a scale from 0 to 4, with higher scores indicating higher tremor amplitude of the upper limb. The upper limb total score is the sum of these 6 sub-items and ranges from 0 to 24 where larger values represent higher tremor severity.	56 days
Secondary	Change from baseline to Day 56 on the TETRAS-combined upper limb (CUL) score (TETRAS-PS sum of items 4, 6, 7, and 8)	The combined upper limb score is the sum of the 6 sub-item scores of the upper limb item and the handwriting and spirals scores. The combined upper limb score ranges from 0 to 32 where larger values represent higher tremor severity.	56 days
Secondary	Patient Global Impression-Change (PGI-C) score at Day 56	The PGI-C assesses the participant's change in condition. The participant is required to assess their condition relative to Baseline (Pre-dose on Day 1) on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the participant believes the change is drug-related or not.	56 days
Secondary	Change from baseline to Days 14, 28, and 42 on the modified ADL	The modified ADL is a composite sum of items 1 to 11 of the TETRAS-ADL subscale and items 6 and 7 on the TETRAS-PS. The impact to each function is rated on a 5-point Likert scale from 0 to 4. Before calculating the total score, a scoring adjustment is applied to each item score. The modified ADL score is calculated as the sum of all 13 items (with scoring adjustments) and ranges from 0 to 42 where larger values represent increased direct tremor impact to activities of daily living.	Up to 42 days
Secondary	Change from baseline to Days 14, 28, and 42 on the CGI-S	The CGI-S assesses the clinician's impression of the participant's current illness state. The clinician should use his/her total clinical experience with this patient population and rate the current severity of the participant's ET on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).	Up to 42 days
Secondary	Change from baseline to Days 14, 28, and 42 on the TETRAS-ADL total 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 where larger values represent increased direct tremor impact to activities of daily living.	Up to 42 days
Secondary	Change from baseline to Days 14, 28, and 42 on the TETRAS-UL score	Item 4 of the Performance subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). Each sub-item is rated on a scale from 0 to 4, with higher scores indicating higher tremor amplitude of the upper limb. The upper limb total score is the sum of these 6 sub-items and ranges from 0 to 24 where larger values represent higher tremor severity.	Up to 42 days
Secondary	Change from baseline to Days 14, 28, and 42 on the TETRAS-CUL score	The combined upper limb score is the sum of the 6 sub-item scores of the upper limb item and the handwriting and spirals scores. The combined upper limb score ranges from 0 to 32 where larger values represent higher tremor severity.	Up to 42 days
Secondary	CGI-I scores at Days 14, 28, and 42	The CGI-I assesses the participant's improvement (or worsening). The clinician is required to assess the participant's condition relative to pre-treatment on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement/worsening is drug-related or not.	Up to 42 days
Secondary	PGI-C scores at Days 14, 28, and 42	The PGI-C assesses the participant's improvement (or worsening). The participant is required to assess their condition relative to Baseline (Pre-dose on Day 1) on a 7-point scale from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the participant believes the improvement/worsening is drug-related or not.	Up to 42 days
Secondary	Change from baseline to Day 42 on the TETRAS-PS total score	There are 9 items covering different body regions in the Performance Subscale. Each Performance Subscale item is rated on a scale of 0 to 4, with higher scores indicating higher tremor severity. Item 4 of the Performance Subscale is the upper limb item. It is comprised of 6 sub-items (4a, 4b, and 4c assessed for both the right and left upper limbs). The Performance subscale score is calculated as the sum of all 9 items and ranges from 0 to 64.	42 days
Secondary	Number of participants with Adverse Events (AE)	The number of participants with Adverse Events (AE) will be reported by preferred term.	Up to 56 days