What side effects are associated with this type of intervention?

Common treatments for Essential Tremor include beta-blockers like propranolol, anticonvulsants such as primidone, and benzodiazepines like clonazepam. Side effects of these treatments can include fatigue, dizziness, nausea, and cognitive impairment. For treatments similar to SAGE-324, which modulate GABA-A receptors, side effects may include sedation, dizziness, and potential dependency with long-term use. It is important to discuss these potential side effects with a healthcare provider to determine the best treatment plan.

What prior FDA approvals exist?

The FDA has approved several treatments for Essential Tremor, though specific approvals for Positive Allosteric Modulators of GABA-A Receptors like SAGE-324 are not detailed in the provided context. Traditional treatments include propranolol and primidone, which are commonly used. Additionally, surgical options such as thalamotomy and deep brain stimulation have shown efficacy. The context does not mention specific FDA approvals for drugs similar to SAGE-324, but ongoing studies suggest a focus on GABA-A receptor modulation as a promising therapeutic approach.

What other types of research exist?

Promising novel alternatives to SAGE-324 for Essential Tremor patients include: 1) Cala Trio, a non-invasive neuromodulation device that delivers electrical stimulation to the wrist, which has shown efficacy in reducing tremor symptoms. 2) Focused Ultrasound (FUS) thalamotomy, a non-invasive surgical procedure that targets the thalamus to reduce tremor. 3) TMS (Transcranial Magnetic Stimulation), which uses magnetic fields to stimulate nerve cells in the brain and has shown potential in reducing tremor severity. These alternatives offer different approaches to managing ET and may be considered in treatment plans for 2024.

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GABA receptor modulator

SAGE-324 for Essential Tremor

Phase 2

Waitlist Available

Research Sponsored by Sage Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (eg, voice, head), task- and position-specific tremors, sudden tremor onset, or evidence of stepwise deterioration of tremor.

Scores of at least 6 in the total TETRAS Performance Subscale Item 4 score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) at both Screening and pre-dose on Day 1

Must not have

Previous procedure for the treatment of ET such as deep brain stimulation, brain lesioning, or magnetic resonance (MR) guided procedure

Use of Cala Trio bracelet for the treatment of ET from two weeks prior to Day 1 through Day 97

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to day 91

Summary

This trial is testing a medication to see how well it reduces arm and hand tremors in people with essential tremor. The goal is to find the most effective dose that helps calm the brain's overactive signals causing the tremors.

Who is the study for?

This trial is for adults with Essential Tremor (ET) that's lasted at least 3 years. Participants must be willing to stop their ET medications before starting the study, except propranolol if it's been taken steadily. They can't have other neurological issues or use certain treatments like the Cala Trio bracelet, and they shouldn't have a history of substance abuse or dependence.

What is being tested?

The trial tests SAGE-324 against a placebo to see how different doses affect arm tremors in people with ET. It looks at whether one dose works better than another when no other tremor medications are used.

What are the potential side effects?

Possible side effects aren't specified here, but generally, participants might experience reactions related to the nervous system due to the nature of SAGE-324 targeting tremors.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I do not have other major nerve system symptoms like uncontrolled movements or balance issues.

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My dominant arm's function scores at least 6 on a specific test.

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I have been diagnosed with Essential Tremor in my arms for over 3 years, with no other major neurological issues.

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I have been diagnosed with Essential Tremor in my arms for at least 3 years.

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My upper limb tremor score is 12 or more.

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I can perform most daily activities by myself.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have undergone a procedure like deep brain stimulation for essential tremor.

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I have been using the Cala Trio bracelet for my ET for at least two weeks.

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I have tremors due to a functional neurological condition.

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I am currently taking propranolol for a condition that is not essential tremor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to day 91

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to day 91

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to day 91 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change From Baseline in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Total Score on Day 91 in the Monotherapy Cohort

Secondary study objectives

Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort

Side effects data

From 2021 Phase 2 trial • 69 Patients • NCT04305275

68%

Somnolence

38%

Dizziness

15%

Balance disorder

15%

Fatigue

12%

Diplopia

12%

Gait disturbance

12%

Dysarthria

Myoclonus

Disturbance in attention

Paraesthesia

Diarrhoea

Mental status changes

Lethargy

Speech disorder

Headache

Asthenia

Insomnia

Urinary tract infection

Dehydration

Transient ischaemic attack

Coordination abnormal

100%

80%

60%

40%

20%

Study treatment Arm

SAGE-324 Matched Placebo

SAGE-324 60 mg

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: SAGE-324 60 mgExperimental Treatment1 Intervention

Participants will receive SAGE-324: 15 mg, 30 mg, 45 mg, and 60 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Group II: SAGE-324 30 mgExperimental Treatment1 Intervention

Participants will receive SAGE-324, 30 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Group III: SAGE-324 15 mgExperimental Treatment1 Intervention

Participants will receive SAGE-324, 15 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Group IV: SAGE-324 Matched PlaceboPlacebo Group1 Intervention

Participants will receive SAGE-324 matched placebo, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324 matched placebo, oral tablets, once daily (QD), in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324 matched placebo, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 milligrams (mg) of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

SAGE-324

2020

Completed Phase 2

~70

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Essential Tremor (ET) treatments often target the modulation of neurotransmitter systems to reduce tremor severity. SAGE-324, a Positive Allosteric Modulator of GABA-A receptors, enhances the inhibitory effects of GABA, leading to reduced neuronal excitability and tremor. This mechanism is crucial for ET patients as it directly addresses the hyperactivity in the central nervous system that contributes to tremor. Other common treatments include beta-blockers like propranolol, which reduce tremor by blocking peripheral adrenergic receptors, and anticonvulsants like primidone, which also enhance GABAergic activity. Understanding these mechanisms helps in tailoring treatments to effectively manage symptoms and improve quality of life for ET patients.

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