ES-481 for Essential Tremor

Not currently recruiting at 1 trial location

Overseen By Robert Niecestro, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: ES Therapeutics Australia Pty Ltd

Must be taking: Anti-tremor medications

Must not be taking: Tremorgenic drugs

Disqualifiers: Pregnancy, Alcohol dependence, Parkinson's, others

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

Compensation: Varies

Number of Visits: 117

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ES-481 to determine its safety and tolerability for people with essential tremor, a condition causing uncontrollable shaking, usually in the hands. Participants will receive either the experimental treatment or a placebo (a pill with no active medicine) to compare results. This offers an opportunity for those who have experienced essential tremor for at least three years, affecting their daily activities, to potentially benefit from a new treatment option. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants must be on a stable dose of anti-tremor medication for at least four weeks before the study and must continue with the same dose during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ES-481 is currently being tested for safety in treating essential tremor. Studies have found that most patients tolerate the treatment well, with no major reports of serious side effects. The drug is also under investigation for other conditions, such as epilepsy, suggesting researchers consider it fairly safe. As this trial is in an early stage, it focuses on assessing safety and how the body processes the drug. Researchers closely monitor for any side effects or issues. Overall, ES-481 appears promising in terms of safety so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for essential tremor?

Unlike the standard treatments for essential tremor, which often include beta-blockers or anti-seizure medications, ES-481 offers a novel approach. Most current therapies work by calming the nervous system overall, but ES-481 targets specific neural pathways to reduce tremors more directly. This precision could lead to fewer side effects and improved effectiveness, giving researchers hope for a more tailored and effective treatment option for those living with essential tremor.

What evidence suggests that ES-481 might be an effective treatment for essential tremor?

Research has shown that ES-481, which participants in this trial may receive, may help treat essential tremor. In earlier studies, people taking ES-481 experienced a 68% to 80% improvement in symptoms. This was significantly better than the 38% to 49% improvement in those taking a placebo (a pill with no active medicine), which serves as the comparator in this trial. The highest dose of ES-481 led to an 80% improvement, indicating strong effectiveness. These results suggest that ES-481 could be a useful treatment for essential tremor. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-75 with essential tremor, not caused by other conditions or recent trauma, who haven't had surgery for tremor and are on a stable dose of anti-tremor medication. They must have no history of substance abuse or major psychiatric disorders and agree to avoid alcohol before visits.

Inclusion Criteria

You have been diagnosed with essential tremor which means you have been experiencing shaking in your arms for at least three years, even when you are trying to do something. You may have shaking in other parts of your body as well.

You have never taken perampanel before.

The Subject must have Essential Tremor (ET). ET is defined as at least 1 upper extremity with a tremor score ≥ 1.5 in forward posture, wing beating posture, or finger-to-nose movement using the Performance subscale of The Essential Tremor Rating Assessment Scale (as per by the Tremor Investigation Group criteria).

Exclusion Criteria

You are using an intrauterine device for birth control.

You have had a surgery to permanently prevent pregnancy.

You have experienced nerve system injury or trauma within the last 3 months prior to the start of your tremors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive ES-481 or placebo with escalating doses over 4 weeks

4 weeks

Visits on Days 1, 8, 15, 22

Washout

Participants undergo a washout period between treatment periods

2 weeks

Treatment Period 2

Participants receive ES-481 or placebo with escalating doses over 4 weeks

4 weeks

Visits on Days 44, 51, 58, 65

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Visit on Day 72

What Are the Treatments Tested in This Trial?

Interventions

• ES-481
• Placebo

Trial Overview The trial is testing ES-481's safety, tolerability, and how the body processes it in adults with essential tremor compared to a placebo. It's designed to see if this new treatment can help control the involuntary shaking characteristic of this condition.

How Is the Trial Designed?

Group I: ES-481 Experimental Treatment 1 Intervention

Week 1 - 25 mg qd (2 x 25 mg capsule in the mornings Days 1 to 7 in Treatment Period 1 and Days 44 to 50 in Treatment Period 2) Week 2 - 50 mg bid (2 x 25 mg capsule in the mornings and 2 x 25 mg capsules in the evening on Days 8 to 14 in Treatment Period 1 and Days 51 to 57 in Treatment Period 2) Week 3 - 75 mg bid (2 x 25 mg capsule in the mornings and 2 x 25 mg capsules in the evening on Days 15 to 21 in Treatment Period 1 and Days 58 to 64 in Treatment Period 2) Week 4 - 75 mg bid (2 x 25 mg capsule in the mornings and 2 x 25 mg capsules in the evening on Days 22 to 28 in Treatment Period 1 and Days 65 to 71 in Treatment Period 2)

Group II: Placebo Placebo Group 1 Intervention

Placebo will be dosed at the same quantity and frequency as ES-481 just as Placebo HPMC capsules

Who Is Running the Clinical Trial?

ES Therapeutics Australia Pty Ltd

Lead Sponsor

Trials

3

Recruited

50+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05234762

Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult ... This Pilot Phase 2A study will investigate the safety, tolerability, and pharmacokinetics (PK) of ES-481 in adult patients with essential tremor.

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000206132

Efficacy and Safety of ES-481, a Novel TARP Inhibitor, in ... Subjects had 68%–80% improvements on ES-481 treatment, compared to 38%–49% under placebo treatment. For the top dose of ES-481 treatment subjects had 80% ...

3. withpower.com withpower.com/trial/phase-2-tremor-essential-10-2021-f84d1

ES-481 for Essential Tremor · Info for Participants This trial will test a new drug called ES-481 in adults with essential tremor to see if it is safe and well-tolerated. Researchers will study how the drug ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9346245/

A Systematic Review of the Literature - PMC - PubMed Central Essential tremor (ET) is one of the most common tremor disorders in the world with an estimated incidence of 0.3% overall (increasing over the lifespan to 5% in ...

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05234762?keyword=%22Tremor%22

Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult ... This Pilot Phase 2A study will investigate the safety, tolerability, and pharmacokinetics (PK) of ES-481 in adult patients with essential tremor. Criteria:.

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05234762/efficacy-safety-and-pharmacokinetics-of-es-481-in-adult-patients-with-essential-tremors

Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult ... This Pilot Phase 2A study will investigate the safety, tolerability, and pharmacokinetics (PK) of ES-481 in adult patients with essential tremor ...

7. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/es-481-es-therapeutics-epilepsy-likelihood-of-approval/

ES-481 by ES Therapeutics for Epilepsy: Likelihood of ... ES-481 (CERC-611) is under development for the treatment of essential tremor and drug resistant epilepsy. The drug candidate is administered orally.