PRAX-944 for Essential Tremor

(Essential1 Trial)

No longer recruiting at 38 trial locations

Overseen By Head of Pharmacovigilance, Praxis Precision Medicines

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Praxis Precision Medicines

Must not be taking: Benzodiazepines, Sleep medications

Disqualifiers: Parkinson's, Huntington's, Alzheimer's, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of PRAX-944, a new potential drug for treating essential tremor, a condition causing uncontrollable shaking, usually in the hands. Researchers aim to determine the optimal dose and compare its efficacy to a placebo. The study includes several phases, with some participants receiving varying dosages of PRAX-944 and others receiving a placebo. It suits individuals who have experienced essential tremor symptoms for at least three years and face moderate to severe difficulties in daily activities due to the tremor. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

If you're taking medication for Essential Tremor, you need to be on a stable dose for at least a month before the trial and keep it stable during the trial. If you're taking primidone, you'll need to stop it 14 days before starting the trial.

Is there any evidence suggesting that PRAX-944 is likely to be safe for humans?

Research has shown that PRAX-944 is well tolerated in clinical studies. Specifically, participants have managed doses up to 120 mg per day. Some studies noted a decrease in tremor strength, indicating the medicine's effectiveness. While all treatments can have side effects, current data suggests that PRAX-944 is safe for humans at the tested doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Essential Tremor?

PRAX-944 is unique because it targets essential tremor with a novel approach, potentially offering a more effective treatment than current medications like propranolol and primidone. Unlike these standard options, which often focus on symptom management, PRAX-944 is designed to modulate specific neural pathways involved in tremor generation, potentially leading to better control of symptoms. Researchers are excited about PRAX-944 because it offers a promising mechanism of action that could enhance quality of life for patients with essential tremor by directly addressing the underlying neural activity.

What evidence suggests that PRAX-944 might be an effective treatment for Essential Tremor?

Research has shown that PRAX-944, the investigational treatment in this trial, may help treat essential tremor. One study reported a 42% reduction in hand and arm tremors, which is promising. Another study found that tremors decreased significantly without affecting movement, suggesting it might be a well-tolerated option. Early animal studies also support these findings, showing a 50% to 72% reduction in tremors. These results suggest that PRAX-944 could help manage symptoms for those with essential tremor. ^{2 5 6 7 8}

Who Is on the Research Team?

Director, Clinical Development

Principal Investigator

Praxis Precision Medicines

Are You a Good Fit for This Trial?

Inclusion Criteria

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.

Your body mass index (BMI) is between 18 and 40.

Your body mass index (BMI) should be between 18 and 40 kg/m2.

Exclusion Criteria

You have a history of specific medical, neurological, or psychiatric conditions that can cause tremors, such as Parkinson's disease, Alzheimer's disease, or a family history of Fragile X syndrome.

You are not using certain types of medication that could affect the evaluation of tremors.

You have had a problem with drugs or alcohol in the past, but you have been doing well for at least 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral dosing of PRAX-944 with titration over 56 days

8 weeks

Multiple visits for titration and monitoring

Extension Double-blind Lead-in

Participants receive double-blind oral dosing of PRAX-944 for 43 days

6 weeks

Extension Open-label

Participants receive open-label flexible dosing of PRAX-944 for 469 days

67 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PRAX-944

How Is the Trial Designed?

Group I: Regimen 2 Experimental Treatment 4 Interventions

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 II: Regimen 1 Experimental Treatment 4 Interventions

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 III: Regimen 3 Placebo Group 4 Interventions

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.

Who Is Running the Clinical Trial?

Praxis Precision Medicines

Lead Sponsor

Trials

11

Recruited

1,300+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05021978

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

2. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-topline-results-essential1

Praxis Precision Medicines Announces Topline Results ... The results from Essential1 illustrate the clear potential of ulixacaltamide as an effective and well tolerated treatment for people with essential tremor.

3. neurology.org neurology.org/doi/10.1212/WNL.98.18_supplement.1557

PRAX-944-221: A Phase 2 Clinical Trial Evaluating the ... Preliminary results revealed a mean reduction in TETRAS-UL score of 2.83 points on Day 14, corresponding to a 42% reduction in upper limb tremor ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9310641/

Translational Pharmacology of PRAX‐944, a Novel T‐Type ... Results. In rats, PRAX‐944 dose‐dependently reduced tremor by 50% and 72% at 1 and 3 mg/kg doses, respectively, without locomotor side effects. ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/praxis-precision-essential-tremor-therapy/

Praxis Precision Medicines reports data from essential ... Praxis Precision Medicines has reported topline data from the Phase IIb Essential1 trial of ulixacaltamide (PRAX-944) to treat essential tremor (ET).

6. praxismedicines.com praxismedicines.com/wp-content/uploads/2023/09/Olhaye-et-al_MDS2022_944-221_Abstract-951_QRcode.pdf

A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, ... A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults with Essential Tremor. Omar ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000206620

The Future of Clinical Trial Design in Essential Tremor (P3 ... An innovative, multi-study Phase 3 program to definitively assess safety and efficacy of ulixacaltamide (PRAX-944) in essential tremor (ET).

8. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-present-data-prax-944-essential

Praxis Precision Medicines to Present Data from PRAX ... In clinical trials to date, treatment with PRAX-944 up to 120mg/day has been well tolerated and showed both a reduction in tremor amplitude and ...