Staccato Alprazolam for Epilepsy

Recruiting at 173 trial locations

Overseen By UCB Cares

Age: Any Age

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Single administration

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Staccato alprazolam, an inhaled medication, to determine if it can quickly stop seizures and prevent their immediate recurrence. Participants will inhale either this treatment or a placebo to compare effects. The trial seeks individuals with epilepsy who experience frequent, long seizures and are on stable medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for epilepsy.

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.

Is there any evidence suggesting that Staccato alprazolam is likely to be safe for humans?

Research has shown that Staccato alprazolam is generally safe for people with epilepsy. In previous studies, both 1.0 mg and 2.0 mg doses effectively stopped seizures quickly and were safe for patients. Another study found that alprazolam, when administered using the Staccato device, was absorbed quickly by most patients without major safety issues. Researchers primarily assessed safety by monitoring side effects or serious problems after treatment, and these were controlled. Overall, the evidence suggests that this treatment is safe for humans. ^{1 2 3 4 5}

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

Staccato alprazolam is unique because it's delivered through inhalation, allowing for rapid absorption and potentially quicker relief from epileptic seizures. Unlike traditional oral medications, which can take longer to take effect, this method offers a faster response time—crucial during an acute seizure. Researchers are excited about this treatment because it combines the well-known efficacy of alprazolam with an innovative delivery system, potentially offering a more immediate therapeutic benefit for epilepsy patients.

What evidence suggests that Staccato alprazolam might be an effective treatment for epilepsy?

In this trial, participants will be randomized to receive either Staccato alprazolam or a placebo. Research has shown that Staccato alprazolam can quickly stop seizures. One study found that both 1.0 mg and 2.0 mg doses were effective and safe for patients. Another study demonstrated that it significantly shortened seizure duration. Importantly, many patients did not experience new seizures for up to two hours after using the treatment. This medication is inhaled, which helps it work quickly. Overall, evidence suggests that Staccato alprazolam is promising for effectively managing seizures. ^{1 5 6 7 8}

Who Is on the Research Team?

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Are You a Good Fit for This Trial?

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

My recent brain scans show no progressive neurological disorder.

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

I agree to use birth control and not donate sperm for 7 days after treatment.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Staccato alprazolam

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.

How Is the Trial Designed?

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.

Staccato alprazolam is already approved in United States, European Union for the following indications:

Approved in United States as Alprazolam for:

• Anxiety disorder
• Panic disorder

Approved in European Union as Alprazolam for:

• Anxiety disorder
• Panic disorder

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10107237/

A randomized phase 2b efficacy study in patients with seizure ... Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated.

2. neurologylive.com neurologylive.com/view/advancing-rest-in-epilepsy-with-staccato-alprazolam

Advancing REST in Epilepsy with Staccato Alprazolam The study's results demonstrated that Staccato alprazolam effectively reduced seizure duration, with a significant percentage of patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03478982

NCT03478982 | Inpatient, Dose-Ranging Study of Staccato ... Percentage of participants with onset of a predictable seizure through 2 minutes post dosing with study drug and no recurrence of seizure activity within 2 ...

4. ucb-usa.com ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-presents-new-data-on-impact-and-burden-of-epilepsy-at-2024-american-epilepsy-society-aes-meeting

UCB Presents New Data on Impact and Burden of Epilepsy ... Staccato® alprazolam is an investigational treatment (Phase 3) currently being studied to assess its potential to rapidly terminate seizures at ...

5. aesnet.org aesnet.org/abstractslisting/a-two-part--phase-2b-efficacy-study-of-staccato%C2%AE-alprazolam-inhaler-in-patients-with-epilepsy-with-a-predictable-seizure-pattern--results-from-part-1-and-early-results-from-part-2

Phase-2b-Efficacy-Study-of-Staccato®-Alprazolam-Inhaler-in ... A proof-of-concept study showed that Staccato alprazolam rapidly suppressed epileptiform activity in photosensitive patients (pts). ... Methods: ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.18643?af=R

Pharmacokinetics and tolerability of single‐dose Staccato ... Overall, alprazolam was rapidly absorbed in most adolescent patients with epilepsy following administration with the Staccato device, and no ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05077904

NCT05077904 | A Study to Test the Efficacy and Safety of ... The purpose of the study is to assess the success of a single administration of Staccato alprazolam compared with placebo both in rapidly terminating a seizure ...

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000204981

Pharmacokinetics of Staccato® Alprazolam in Healthy ... Primary safety endpoints were treatment-emergent adverse events (TEAEs) and serious TEAEs in Japanese and Chinese participants. Results: 10 ...