What side effects are associated with this type of intervention?

Common treatments for epilepsy that enhance GABA-A receptor activity, such as benzodiazepines (e.g., alprazolam, diazepam, lorazepam), are associated with several side effects. These include sedation, dizziness, impaired coordination, and cognitive dysfunction. Long-term use can lead to dependence, tolerance, and withdrawal symptoms. Additionally, benzodiazepines can cause respiratory depression, particularly when combined with other central nervous system depressants.

What prior FDA approvals exist?

Several FDA-approved treatments for epilepsy work by enhancing GABA-A receptor activity, similar to Staccato alprazolam. Benzodiazepines like diazepam, lorazepam, and clonazepam are commonly used for their rapid action in terminating seizures by enhancing the inhibitory effect of GABA at the GABA-A receptor. Additionally, barbiturates such as phenobarbital also enhance GABA-A receptor activity and are used in the management of epilepsy. These medications help to inhibit neuronal activity and are effective in controlling various types of seizures.

What other types of research exist?

Promising novel alternatives to Staccato alprazolam for epilepsy patients include ganaxolone, a synthetic neuroactive steroid approved for CDKL5 deficiency disorder, which has shown efficacy in reducing seizure frequency. Additionally, AMPA antagonists of the 2,3-benzodiazepine type, such as GYKI-47261, are being investigated for their broad-spectrum anticonvulsive and neuroprotective effects. These alternatives offer new mechanisms of action and potential benefits for epilepsy management.

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Benzodiazepine

Staccato Alprazolam for Epilepsy

Phase 3

Recruiting

Research Sponsored by UCB Biopharma SRL

Eligibility Criteria Checklist

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

Must have

Participant has had a documented brain computerized tomography or magnetic resonance imaging review, performed after diagnosis of epilepsy and within the 5 years prior to the Screening Visit, that confirms the absence of a progressive neurological disorder

Female participants must not be pregnant, not breastfeeding, and meet specific contraceptive criteria

Must not have

Participant has a history or presence of known nonepileptic seizures which cannot be distinguished from qualifying epileptic seizures

Participant has a known hypersensitivity to any components of the IMP or comparable drugs (and/or an investigational device) as stated in this protocol or to albuterol (or similar bronchospasm rescue medication if needed to meet country-specific requirements)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from start of imp treatment up to the safety follow-up visit (week 19)

Awards & highlights

Pivotal Trial

Summary

This trial tests if inhaling Staccato alprazolam can quickly stop seizures and prevent them from coming back. It targets patients who need fast-acting seizure control. Staccato alprazolam is a potential therapy for rapid epileptic seizure termination, delivered via a breath-actuated device for rapid systemic exposure.

Who is the study for?

This trial is for people aged 12 and older with focal or generalized epilepsy who have had at least four prolonged seizures in the past six months. They must be on a stable medication regimen, not pregnant or breastfeeding, and agree to use contraception. Exclusions include drug abuse within the last year, sensitivity to alprazolam or similar drugs, certain respiratory issues, glaucoma, long QT syndrome, unstable psychiatric disorders, recent changes in VNS therapy settings.

What is being tested?

The study tests Staccato alprazolam's ability to quickly stop a seizure within 90 seconds without recurrence for up to two hours compared to a placebo. Participants will receive one dose of either the actual drug or placebo during an episode.

What are the potential side effects?

Staccato alprazolam may cause drowsiness, dizziness, headache, blurred vision and can affect coordination. It might also lead to dependency if used regularly over time.

Eligibility Criteria

Inclusion Criteria

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

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My recent brain scans show no progressive neurological disorder.

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I am not pregnant, not breastfeeding, and follow specific birth control measures.

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I am 12 years old or older.

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I have been diagnosed with epilepsy and have a history of long-lasting seizures.

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I've had 4 or more long seizures in the last 6 months, with 2 happening in the last 3 months.

Exclusion Criteria

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

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I have seizures that can't be told apart from epileptic ones.

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I am not allergic to the trial medication or similar drugs, including albuterol.

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I have been diagnosed with atrial fibrillation or mitral stenosis.

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I regularly use opioids or sedatives.

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I tested positive for COVID-19 and needed treatment for severe symptoms.

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I have or had acute narrow-angle glaucoma.

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My liver condition is currently unstable.

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I have severe allergies or breathing problems.

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I have or my family has a history of long QT syndrome or sudden unexplained fainting.

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I am on medication for a major psychiatric disorder and expect changes to it during the study.

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I have a serious lung condition that is not mild asthma.

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I cannot take alprazolam due to my health condition.

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I am currently taking medication that strongly affects liver enzyme CYP3A4.

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I am regularly taking medication that affects my heart and blood pressure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from start of imp treatment up to the safety follow-up visit (week 19)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from start of imp treatment up to the safety follow-up visit (week 19)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from start of imp treatment up to the safety follow-up visit (week 19) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Treatment success for the treated seizure with no recurrence up to 2 hours

Treatment success for the treated seizure within 90 seconds after investigational medicinal product (IMP) administration

Secondary study objectives

Frequency of respiratory treatment emergent adverse events (TEAEs)

Number of subsequent seizure(s) up to 2 hours after IMP administration

Time from IMP administration to cessation of the treated seizure

+3 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Staccato alprazolam ArmExperimental Treatment1 Intervention

Participants randomized to this arm will receive a single dose of Staccato alprazolam by inhalation.

Group II: Placebo ArmPlacebo Group1 Intervention

Participants randomized to this arm will receive a single dose of placebo by inhalation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Staccato alprazolam

2022

Completed Phase 1

~30

0 / 19Eligibility 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

Common treatments for epilepsy often target the modulation of neuronal excitability to prevent seizures. Staccato alprazolam, for instance, enhances GABA-A receptor activity, increasing inhibitory neurotransmission and rapidly terminating seizures. Other treatments, such as lamotrigine and valproate, work by stabilizing neuronal membranes through sodium channel modulation and reducing excitatory neurotransmitter release. Pregabalin and gabapentin block calcium channels, decreasing neurotransmitter release and neuronal excitability. These mechanisms are vital for epilepsy patients as they help maintain seizure control and improve quality of life by reducing the frequency and severity of seizures.

[How do antiepileptic drugs work?].