Ulixacaltamide for Essential Tremor

Overseen By Head of Pharmacovigilance, Praxis Precision Medicines

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Praxis Precision Medicines

Must not be taking: Benzodiazepines, Sleep medications

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

600 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to compare ulixacaltamide and placebo treatment in essential tremor. The main question it aims to answer is: • Is ulixacaltamide a safe and efficacious treatment for patients with essential tremor? Participants will be asked to participate in one of two clinical studies where they will be treated with either ulixacaltamide or placebo for a period of up to 12 weeks. After the controlled study completion, they will be eligible to participate in a long-term, open-label safety study and be treated with ulixacaltamide.

Will I have to stop taking my current medications?

If you are currently taking medication for essential tremor, you must be on no more than one medication and keep the dose stable throughout the study. You cannot use certain medications like primidone within two weeks before the study and during the study. If you use propranolol as needed, you must stop after the first day of screening.

How is the drug Ulixacaltamide different from other drugs for essential tremor?

Ulixacaltamide (PRAX-944) is unique because it is being specifically studied for its potential to treat essential tremor, whereas other drugs like pramipexole and acetazolamide are primarily used for other conditions such as Parkinson's disease and have mixed results in treating essential tremor. This makes Ulixacaltamide a novel option as it may offer a more targeted approach for essential tremor. ^{1 2 3 4 5}

Research Team

Director, Clinical Development

Principal Investigator

Praxis Precision Medicines

Eligibility Criteria

This trial is for adults with essential tremor (ET) who are on a stable dose of no more than one ET medication, have not used certain drugs like primidone recently, and do not have other conditions that could cause tremors. They must be willing to avoid as-needed ET meds during the study, use contraception if applicable, and have a BMI between 18-40 kg/m2.

Inclusion Criteria

Women of childbearing potential must undertake pregnancy tests, with a documented negative serum pregnancy test at Screening on Day -28, negative urine pregnancy tests Baseline (Day 1) prior to administration of study drug, throughout the intervention periods (as outlined in the SoA) and at the SFU or ED Visit, as appropriate.

I am on 1 or no essential tremor medications, with a stable dose for the last month.

I have been diagnosed with Essential Tremor due to my shaking when moving or standing.

Exclusion Criteria

I have been using the Cala kIQ™ device for my condition for the last 14 days or will continue to use it during the study.

I am not on medications that strongly affect liver enzymes and can't stop them for the study.

I have received a botulinum toxin injection for essential tremor within the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ulixacaltamide or placebo for up to 12 weeks in a double-blind, parallel design or randomized withdrawal format

12 weeks

Regular visits as per study protocol

Randomized Withdrawal

Participants undergo a randomized withdrawal phase to assess maintenance of response

4 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Safety Study

Eligible participants continue in an open-label extension to assess long-term safety of ulixacaltamide

52 weeks

Treatment Details

Interventions

• Ulixacaltamide

Trial Overview The trial tests ulixacaltamide against a placebo in patients with essential tremor over 12 weeks to see if it's safe and effective. After this phase, participants can join a longer-term study where everyone gets ulixacaltamide.

Participant Groups

Group I: Randomized Withdrawal Experimental Treatment 2 Interventions

Double-blind Part: Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, 42 days of 60 mg Randomized Withdrawal Part: Following double-blind part: 1:1 randomization to placebo or 60 mg ulixacaltamide for 28 days

Group II: Parallel Design: ulixacaltamide arm Experimental Treatment 1 Intervention

Double-blind Part: Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, 70 days of 60 mg

Group III: Long-term Safety Study: Parallel Design and Randomized Withdrawal rollovers Experimental Treatment 1 Intervention

Open-label Part for patients previously on placebo: Oral dosing, once daily in the morning with titration over 14 days to 60 mg ulixacaltamide: 7 days of 20 mg, 7 days of 40 mg, up to 351 days of 60 mg Open-label Part for patients previously on 60 mg ulixacaltamide: Oral dosing, once daily in the morning up to 365 days 60 mg ulixacaltamide

Group IV: Long-term Safety Study: Essential1 rollovers Experimental Treatment 1 Intervention

Open-label Part: Oral dosing, once daily in the morning up to one year (365 days) of 60 mg ulixacaltamide

Group V: Parallel Design: placebo arm Placebo Group 1 Intervention

Double-blind Part: Oral dosing, once daily in the morning: 84 days of placebo

Who Is Running the Clinical Trial?

Praxis Precision Medicines

Lead Sponsor

Trials

11

Recruited

1,300+

Findings from Research

Acetazolamide, a carbonic anhydrase inhibitor, significantly reduced tremor severity in 24 patients with essential tremor, indicating its potential efficacy as a treatment.

Despite common side effects, more than half of the patients chose to continue using acetazolamide, suggesting that they found the benefits of tremor reduction outweighed the adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on essential tremor: an open-label trial. Busenbark, K., Pahwa, R., Hubble, J., et al.[2019]

In a pilot study involving 10 patients with tremor-dominant Parkinson's disease, both pramipexole and pergolide significantly reduced tremor scores compared to placebo, indicating their effectiveness in managing this symptom.

However, pergolide was associated with a higher incidence of nausea and vomiting compared to pramipexole, suggesting that while both medications are effective, pramipexole may be a safer option regarding side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease. Navan, P., Findley, LJ., Jeffs, JA., et al.[2018]

A 59-year-old woman with uremia undergoing hemodialysis experienced fatal intoxication after taking amantadine and pramipexole for Parkinsonian tremor, leading to severe symptoms like myoclonus, ataxia, and confusion.

This case emphasizes the potential dangers of using amantadine and pramipexole in patients with uremia, suggesting that these medications may pose significant risks even when patients are receiving hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal intoxication using amantadine and pramipexole in a uremic patient. Hong, CT., Sun, Y., Lu, CJ.[2018]

In a 16-week pilot study involving 29 patients with essential tremor, pramipexole significantly reduced tremor severity by 52% and improved quality of life, with 72.4% of participants responding positively to treatment.

The higher dosage of 2.1 mg/day was more effective than 1.05 mg/day, although both immediate- and extended-release formulations showed similar efficacy, indicating potential for pramipexole as a treatment option for essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pramipexole may be an effective treatment option in essential tremor. Herceg, M., Nagy, F., Pál, E., et al.[2022]

In a study of 22 patients with essential tremor, alprazolam was found to be more effective than placebo and equally effective as primidone, suggesting it can be a viable alternative treatment.

Acetazolamide did not show significant benefits compared to placebo, indicating it may not be a suitable option for managing essential tremor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide. Gunal, DI., Afşar, N., Bekiroglu, N., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on essential tremor: an open-label trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease. [2018]

3. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Fatal intoxication using amantadine and pramipexole in a uremic patient. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Pramipexole may be an effective treatment option in essential tremor. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide. [2019]