Staccato Alprazolam for Seizures

Recruiting at 161 trial locations

Overseen By UCB Cares

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: UCB Biopharma SRL

Must be taking: Staccato alprazolam

Must not be taking: CYP3A4 inhibitors, Opioids, Sedatives, Beta blockers

Disqualifiers: Alcohol/drug use disorder, Airway hypersensitivity, Chronic pulmonary disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 48 months

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is studying the long-term safety and tolerability of Staccato alprazolam, a fast-acting inhaled medication for anxiety and panic disorders. Staccato alprazolam is a fast-acting inhaled formulation of alprazolam, which has been widely used and studied for its efficacy in treating anxiety and panic disorders.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to join this trial. Specifically, you cannot take strong CYP3A4 inhibitors (like some antifungal medications), opioids, sedative hypnotics, or nonselective beta blockers on a regular basis.

What data supports the effectiveness of the drug Staccato alprazolam for seizures?

Research shows that Staccato alprazolam, delivered through a special device for quick absorption, may rapidly stop seizures in patients with predictable seizure patterns. This is similar to how other fast-acting benzodiazepines, like midazolam, are effective in quickly managing seizures. ^{1 2 3 4 5}

Is Staccato Alprazolam safe for use in humans?

The safety of Staccato Alprazolam was evaluated in a study where it was used to quickly stop seizures in a small group of patients. The study was conducted under direct supervision, suggesting careful monitoring of safety, but specific safety outcomes were not detailed in the available information. ^{1 6 7 8 9}

How is the drug Staccato alprazolam different from other seizure treatments?

Staccato alprazolam is unique because it uses a breath-actuated device to deliver the drug directly into the lungs, allowing for rapid absorption and quick seizure termination. This method is different from traditional oral or intravenous benzodiazepines, which may not act as quickly. ^{1 10 11 12 13}

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 prolonged seizures. They must have a caregiver to monitor them, no recent severe respiratory issues, no drug abuse in the past year, not be allergic to alprazolam or similar drugs, and should not take certain medications like strong CYP3A4 inhibitors.

Inclusion Criteria

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

I have completed a study with Staccato alprazolam.

Participant must have a study caregiver ≥18 years of age at the time of signing the informed consent; the study caregiver(s) must be able to recognize and observe the participant's seizures

Exclusion Criteria

I have or had acute narrow-angle glaucoma.

I have mild asthma or other allergies affecting my breathing but can still participate.

I have had a major seizure episode in the last 8 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Staccato alprazolam by inhalation to evaluate long-term safety and tolerability

48 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive Staccato alprazolam to assess long-term safety and tolerability

Long-term

Treatment Details

Interventions

• Staccato alprazolam

Trial Overview The study tests Staccato alprazolam's long-term safety and tolerability in patients with epilepsy experiencing prolonged seizures. Participants previously involved in specific Staccato alprazolam studies are eligible.

Participant Groups

Group I: Staccato alprazolam Experimental Treatment 1 Intervention

Participants will receive Staccato alprazolam 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

Findings from Research

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]

Three approved rescue therapies for treating seizure clusters in the U.S. are diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray, with diazepam rectal gel being effective but potentially socially uncomfortable for adults and adolescents.

Midazolam and diazepam nasal sprays offer a rapid and socially acceptable alternative to rectal administration, allowing for easier self-administration during seizure clusters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue Treatments for Seizure Clusters. Kotloski, RJ., Gidal, BE.[2022]

Midazolam nasal spray (MDZ-NS) has been shown to be effective in treating seizure clusters, with a significant success rate in terminating seizures within 10 minutes and maintaining seizure-free status for at least six hours, compared to placebo.

The 5 mg dose of MDZ-NS was found to be as safe as a placebo, indicating that it is a well-tolerated option for patients aged 12 years and older experiencing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Evaluation of the Efficacy and Safety of Midazolam Nasal Spray in Patients With Seizure Clusters: A Systematic Review and Meta-Analysis. Niraj, N., Mahajan, S., Prakash, A., et al.[2023]

Clobazam, a 1,5-benzodiazepine, has been shown to significantly reduce seizure frequency by 65% in patients with refractory epilepsy, making it an effective adjunctive therapy.

While clobazam is generally well tolerated with minimal cognitive impairment, it can cause sedation in some patients, and about 36% may develop tolerance over time, necessitating careful management of dosage and withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of the 1,4- and 1,5-benzodiazepines in the treatment of epilepsy: the place of clobazam. Robertson, MM.[2022]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

The safety and tolerability of intranasal midazolam in epilepsy. [2014]

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

IM midazolam for status epilepticus in the emergency department. [2019]

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

The influence of diazepam or lorazepam on the frequency of endotracheal intubation in childhood status epilepticus. [2019]

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

Rescue Treatments for Seizure Clusters. [2022]

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

Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy. [2022]

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

The Evaluation of the Efficacy and Safety of Midazolam Nasal Spray in Patients With Seizure Clusters: A Systematic Review and Meta-Analysis. [2023]

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

An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group. [2019]

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

Pharmacokinetics and safety of VALTOCO (NRL-1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri-ictal) and nonseizure (interictal) conditions: A phase 1, open-label study. [2021]

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

Stiripentol in refractory status epilepticus. [2013]

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

Comparison of midazolam and diazepam by the intramuscular route for the control of seizures in a mouse model of status epilepticus. [2019]

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

Effect of anesthetics on neuropathologic sequelae of status epilepticus in rats. [2019]

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

Current status of the 1,4- and 1,5-benzodiazepines in the treatment of epilepsy: the place of clobazam. [2022]