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

NCT ID: NCT05021991

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-14
• Study Completion Date: 2024-02-29

Brief 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.

Conditions

Essential Tremor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Regimen 1

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.

Group Type: EXPERIMENTAL

100 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment with titration

60 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment with titration

Placebo

Intervention Type: DRUG

Once daily oral treatment

Flexibly dosed 20 mg to 100 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment

Regimen 2

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.

Group Type: EXPERIMENTAL

100 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment with titration

60 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment with titration

Placebo

Intervention Type: DRUG

Once daily oral treatment

Flexibly dosed 20 mg to 100 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment

Regimen 3

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.

Group Type: PLACEBO_COMPARATOR

100 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment with titration

60 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment with titration

Placebo

Intervention Type: DRUG

Once daily oral treatment

Flexibly dosed 20 mg to 100 mg PRAX-944

Intervention Type: DRUG

Once daily oral treatment

Interventions

100 mg PRAX-944

Once daily oral treatment with titration

Intervention Type: DRUG

60 mg PRAX-944

Once daily oral treatment with titration

Intervention Type: DRUG

Placebo

Once daily oral treatment

Intervention Type: DRUG

Flexibly dosed 20 mg to 100 mg PRAX-944

Once daily oral treatment

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Praxis Precision Medicines

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Director, Clinical Development

Role: STUDY_DIRECTOR

Praxis Precision Medicines

Locations

Praxis Research Site

Birmingham, Alabama, United States

Praxis Research Site

Little Rock, Arkansas, United States

Praxis Research Site

San Diego, California, United States

Praxis Research Site

Santa Monica, California, United States

Praxis Research Site

Torrance, California, United States

Praxis Research Site

Aurora, Colorado, United States

Praxis Research Site

Boca Raton, Florida, United States

Praxis Research Site

Gainesville, Florida, United States

Praxis Research Site

Jacksonville, Florida, United States

Praxis Research Site

Port Charlotte, Florida, United States

Praxis Research Site

St. Petersburg, Florida, United States

Praxis Research Site

Tampa, Florida, United States

Praxis Research Site

West Palm Beach, Florida, United States

Praxis Research Site

Chicago, Illinois, United States

Praxis Research Site

Kansas City, Kansas, United States

Praxis Research Site

Louisville, Kentucky, United States

Praxis Research Site

Rockville, Maryland, United States

Praxis Research Site

Boston, Massachusetts, United States

Praxis Research Site

Burlington, Massachusetts, United States

Praxis Research Site

Farmington Hills, Michigan, United States

Praxis Research Site

Golden Valley, Minnesota, United States

Praxis Research Site

Las Vegas, Nevada, United States

Praxis Research Site

New York, New York, United States

Praxis Research Site

New York, New York, United States

Praxis Research Site

Cincinnati, Ohio, United States

Praxis Research Site

Philadelphia, Pennsylvania, United States

Praxis Research Site

Georgetown, Texas, United States

Praxis Research Site

Houston, Texas, United States

Praxis Research Site

Round Rock, Texas, United States

Praxis Research Site

Burlington, Vermont, United States

Praxis Research Site

Alexandria, Virginia, United States

Praxis Research Site

Virginia Beach, Virginia, United States

Praxis Research Site

Kirkland, Washington, United States

Praxis Research Site

Spokane, Washington, United States

Praxis Research Site

Milwaukee, Wisconsin, United States

Praxis Research Site

Vancouver, British Columbia, Canada

Praxis Research Site

Halifax, Nova Scotia, Canada

Praxis Research Site

Toronto, Ontario, Canada

Praxis Research Site

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

PRAX-944-222

Identifier Type: -

Identifier Source: org_study_id