Staccato Alprazolam for Epilepsy

Recruiting in Palo Alto (17 mi)

+153 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: UCB Biopharma SRL

Must be taking: Antiseizure medications

Must not be taking: CYP3A4 inhibitors, Opioids

Disqualifiers: Alcohol use disorder, Atrial fibrillation, Chronic pulmonary disorder, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that your current antiseizure medications remain stable, meaning you cannot add or remove any, but dose adjustments are allowed. However, if you are taking benzodiazepines, you cannot adjust the dose. Also, certain medications like strong CYP3A4 inhibitors, opioids, sedative hypnotics, and nonselective beta blockers are not allowed.

What data supports the effectiveness of the drug Staccato Alprazolam for epilepsy?

The study on Staccato Alprazolam suggests it may rapidly stop seizures by delivering alprazolam quickly into the body, which is important for treating prolonged or repetitive seizures. Alprazolam is known to be effective for panic disorders, and its rapid delivery could be beneficial for quickly terminating seizures. ^{1 2 3 4 5}

How is the drug Staccato Alprazolam different from other epilepsy treatments?

Staccato Alprazolam is unique because it uses a breath-actuated device to deliver the drug directly into the deep lung, allowing for rapid absorption and quick seizure termination, unlike traditional methods that may take longer to act. ^{3 6 7 8 9}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Eligibility Criteria

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.

Inclusion Criteria

I have a caregiver over 18 who can observe and recognize my seizures.

My recent brain scans show no progressive neurological disorder.

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

Exclusion Criteria

Your liver enzymes or total bilirubin levels are higher than they should be.

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

I had a cold or similar illness in the last 4 weeks or a lung infection in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Staccato alprazolam or placebo by inhalation to assess seizure termination and recurrence

Single administration

1 visit (in-person)

Follow-up

Participants are monitored for seizure recurrence and adverse events up to 6 hours after treatment

6 hours

Safety Follow-up

Participants are monitored for safety and adverse events up to the Safety Follow-up Visit

Up to 19 weeks

Treatment Details

Interventions

• Placebo (Other)
• Staccato alprazolam (Benzodiazepine)

Trial Overview 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.

Participant Groups

Group I: Staccato alprazolam Arm Experimental Treatment 1 Intervention

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

Group II: Placebo Arm Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

UCB Biopharma SRL

Lead Sponsor

Trials

118

Recruited

23,200+

Jean-Christophe Tellier

UCB Biopharma SRL

Chief Executive Officer since 2015

MD from University of Reims Champagne-Ardenne, Rheumatology specialization from University of Paris V, Executive business programs at Harvard and INSEAD

Dr. Iris Loew-Friedrich

UCB Biopharma SRL

Chief Medical Officer since 2014

MD from University of Leuven, PhD in Medical Sciences from University of Leuven

Findings from Research

Alprazolam is effective for treating panic disorder but can lead to dependence and withdrawal symptoms when stopped.

Carbamazepine, an anticonvulsant with no abuse potential, was successfully used in three cases to reduce withdrawal symptoms from alprazolam, suggesting a potential alternative for managing withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal. Klein, E., Uhde, TW., Post, RM.[2013]

In a study involving 12 adults with refractory epilepsy, oral flumazenil significantly reduced interictal EEG epileptic activity compared to placebo and diazepam, indicating its potential as an effective antiepileptic treatment.

Flumazenil demonstrated a longer duration and greater extent of action in reducing epileptic discharges than diazepam, with a low incidence of adverse events, suggesting it could be a promising option for patients with intractable epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of oral flumazenil on interictal epileptic activity: results of a double-blind, placebo-controlled study. Sharief, MK., Sander, JW., Shorvon, SD.[2019]

In a study involving 116 patients with epilepsy, both 1.0 mg and 2.0 mg doses of Staccato alprazolam effectively terminated seizures within 2 minutes in 65.8% of cases, compared to 42.5% for the placebo, indicating its potential as a rapid treatment for seizures.

Staccato alprazolam was well tolerated, with mild to moderate side effects like cough and somnolence, and no serious adverse events reported, suggesting it is a safe option for seizure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination. French, J., Biton, V., Dave, H., et al.[2023]

In the UK, approximately 1200 epilepsy-related deaths occur annually, with 42% of these deaths potentially avoidable, highlighting the critical need for effective emergency interventions like buccal midazolam for convulsive status epilepticus (SE).

Buccal midazolam is an effective and socially acceptable emergency medication for reducing seizure duration and preventing SE, but its administration requires trained personnel, and current training guidelines need improvement to ensure safe care for patients with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epilepsy emergency rescue training. Shankar, R., Jory, C., Ashton, J., et al.[2020]

A 33-year-old woman developed non-convulsive status epilepticus after starting valproate therapy, indicating a potential adverse effect of this medication when combined with barbexaclone.

The use of flumazenil, a benzodiazepine receptor antagonist, resulted in immediate improvement in her condition, suggesting it may counteract the adverse effects of valproate and other drugs that increase benzodiazepine receptor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus. Steinhoff, BJ., Stodieck, SR.[2019]

Early treatment of seizures in children is crucial to prevent status epilepticus, which can lead to serious health issues; thus, having effective prehospital treatment options is essential.

Nasal and buccal midazolam are practical and effective alternatives for treating pediatric seizures, allowing parents and caregivers to administer treatment easily outside of hospital settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal and buccal treatment of midazolam in epileptic seizures in pediatrics. Ulgey, A., Aksu, R., Bicer, C.[2021]

Intravenous diazepam is the preferred treatment for status epilepticus in hospitals, effectively stopping ongoing seizures.

Buccal midazolam is becoming the preferred option for treating seizures outside of hospitals, replacing rectal diazepam for its ease of administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benzodiazepines in the treatment of epilepsy]. Nakken, KO., Rytter, EM., Brockmeier, F.[2013]

In a case study involving four children with life-threatening illnesses, midazolam (MDZ) effectively stopped status epilepticus seizures within one hour after administration of a high initial dose, demonstrating its rapid efficacy.

No acute adverse events were observed with MDZ treatment, suggesting it is a safe option for managing refractory status epilepticus, although optimal dosing and treatment duration still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of intravenous midazolam in status epilepticus in children]. Lemerle, J., Daoud, P., Moutard, ML., et al.[2019]

Clonazepam (CZP) is a rapidly effective treatment for status epilepticus (SE), showing reliable results in managing this serious neurological disorder.

The use of CZP in SE treatment is associated with mild and transient adverse reactions, indicating it can be safely administered to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clonazepam in the treatment of status epilepticus. Shangguan, Y., Liao, H., Wang, X.[2015]

References

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

Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of oral flumazenil on interictal epileptic activity: results of a double-blind, placebo-controlled study. [2019]

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

A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Epilepsy emergency rescue training. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus. [2019]

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

Nasal and buccal treatment of midazolam in epileptic seizures in pediatrics. [2021]

7. Norway pubmed.ncbi.nlm.nih.gov

[Benzodiazepines in the treatment of epilepsy]. [2013]

8. France pubmed.ncbi.nlm.nih.gov

[Use of intravenous midazolam in status epilepticus in children]. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Clonazepam in the treatment of status epilepticus. [2015]