A Clinical Trial of 2 Doses of PRAX-944 in Participants W... | NCT05021991

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Regimen 1	Experimental	Double-blind Part: Oral dosing, once daily in the morning with titration over 56 days to 100 mg PRAX-944: 7 days of 5 mg, 7 days of 10 mg, 7 days of 20 mg, 7 days of 40 mg, 7 days of 60 mg, 7 days of 80 mg, 14 days of 100 mg Extension Part: Double-blind Lead-in: Oral dosing, once daily in the morning over 43 days: 100 mg PRAX-944 Extension Part: Open-label Flexible PRAX-944 Dosing: Oral dosing, once daily in the morning of 20 mg to 100 mg PRAX-944 for 469 days Crossover Part: Following double-blind lead-in/open-label: 1:1 randomization to placebo or stable dose of PRAX-944 for 21 days followed by cross-over to either placebo or PRAX-944 oral dosing, once daily in the morning with titration over 7 days (3 days at 20 mg, 4 days at 40 mg) to 60 mg (14 days) before returning to open-label part.	Drug: 100 mg PRAX-944 Drug: 60 mg PRAX-944 Drug: Placebo Drug: Flexibly dosed 20 mg to 100 mg PRAX-944
Regimen 2	Experimental	Double-blind Part: Oral dosing, once daily in the morning with titration over 56 days to 60 mg PRAX-944: 7 days of 5 mg, 7 days of 10 mg, 7 days of 20 mg, 7 days of 40 mg, 28 days of 60 mg Extension Part: Double-blind Lead-in: Oral dosing, once daily in the morning with titration over 43 days to 100 mg PRAX-944: 7 days of 80 mg, 36 days of 100 mg Extension Part: Open-label Flexible PRAX-944 Dosing: Oral dosing, once daily in the morning of 20 mg to 100 mg PRAX-944 for 469 days Crossover Part: Following double-blind lead-in/open-label: 1:1 randomization to placebo or stable dose of PRAX-944 for 21 days followed by cross-over to either placebo or PRAX-944 oral dosing, once daily in the morning with titration over 7 days (3 days at 20 mg, 4 days at 40 mg) to 60 mg (14 days) before returning to open-label part.	Drug: 100 mg PRAX-944 Drug: 60 mg PRAX-944 Drug: Placebo Drug: Flexibly dosed 20 mg to 100 mg PRAX-944
Regimen 3

Name	Type	Description	Arm Group Labels	Other Names
100 mg PRAX-944	Drug	Once daily oral treatment with titration	Regimen 1 Regimen 2 Regimen 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
Participant has moderate to severe functional impairment due to tremor as determined by the TETRAS and CGI-S.
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.
Body mass index (BMI) between 18 and 40 kg/m² (inclusive).

Exclusion Criteria:

Sporadically using a benzodiazepine, sleep medication, or anxiolytic that would confound the assessment of tremor.
Trauma to the nervous system within 3 months preceding the onset of tremor.
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
Prior magnetic resonance-guided focused ultrasound or surgical intervention for ET such as deep brain stimulation or thalamotomy.
Botulinum toxin injection for ET in the 6 months prior to Baseline.
Cala trio health device for ET in the 14 days prior to Baseline and throughout the study.
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.

Facility	Status	City	State	ZIP	Country	Contacts
Praxis Research Site		Birmingham	Alabama	35294	United States
Praxis Research Site

ID	Term
D020329	Essential Tremor
D009069	Movement Disorders

ID	Term
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases