A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor (Essential1)

Praxis Precision Medicines

Status and phase: Completed; Phase 2

Conditions: Essential Tremor

Treatments: Drug: Flexibly dosed 20 mg to 100 mg PRAX-944; Drug: 100 mg PRAX-944; Drug: 60 mg PRAX-944; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05021991

PRAX-944-222

Details and patient eligibility

About

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.

Enrollment: 133 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

133 participants in 3 patient groups, including a placebo group

Regimen 1

Experimental group

Description:

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.

Treatment:

Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Drug: Placebo

Drug: 100 mg PRAX-944

Drug: 60 mg PRAX-944

Regimen 2

Experimental group

Description:

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.

Treatment:

Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Drug: Placebo

Drug: 100 mg PRAX-944

Drug: 60 mg PRAX-944

Regimen 3

Placebo Comparator group

Description:

Double-blind Part: Oral dosing, once daily in the morning: 56 days of placebo 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 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: 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.

Treatment:

Drug: Flexibly dosed 20 mg to 100 mg PRAX-944

Drug: Placebo

Drug: 100 mg PRAX-944

Drug: 60 mg PRAX-944