Epilepsy
Conditions
Keywords
Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment
Brief summary
This study is designed to evaluate the efficacy, safety, and tolerability of USL261 compared with that of intranasal (IN) placebo for the treatment of intermittent bouts of increased seizure activity.
Interventions
DRUGUSL261
DRUGPlacebo
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has been admitted to the institution's EMU for seizure characterization or pre-surgical evaluation, or such admission is planned within 28 days * Subject body weight is ≥ 40 kg to ≤ 125 kg (inclusive) * Subject has an established diagnosis of partial or generalized epilepsy
Exclusion criteria
* Subject has history of status epilepticus in the 6 months prior to Screening * Subject has a progressive neurological disorder such as brain tumor, demyelinating disease, or degenerative central nervous system (CNS) disease that is likely to progress in the next 12 months * Subject has respiratory failure (or is at risk for respiratory failure) or other severe cardiorespiratory disease with New York Heart Association Class III or IV functional status, or requires supplemental oxygen * Subject has acute narrow-angle glaucoma * Subject is receiving chronic benzodiazepine treatment (defined as an average of ≥ 4 administrations per week) and cannot safely withdraw from such treatment within the washout period prior to treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Were Seizure-free | 6 hours | A participant was considered seizure-free if he or she completed the 6-hour Treatment Phase without seizures recorded, premature discontinuation of study drug, rescue intervention for acute central respiratory depression adverse event (AE), and alterations to background anti-epileptic drug (AED) therapy. Otherwise, the participant was included in the analysis for seizure-free events with the outcome of seizure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Seizure Following Treatment (TFSFT) | 6 hours | Time to first seizure following treatment was defined as time from treatment with study drug to the onset of the next seizure, rescue intervention (for acute central respiratory depression AE) to maintain subject safety, alterations to background AED therapy, early termination, or 6 hours, whichever came first. |
Countries
Australia, Austria, Belgium, Czechia, Germany, Lithuania, Spain, United States
Participant flow
Pre-assignment details
188 eligible subjects entered Pretreatment Observation during which they were monitored in EMU for seizure events. Only subjects who met entry criteria and presented with seizure events meeting the treatment decision criteria were eligible to enter the Treatment Phase. Participant flow represents subjects who took at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| USL261 5 mg intranasal midazolam
USL261 | 31 |
| Placebo intranasal placebo
Placebo | 31 |
| Total | 62 |
Baseline characteristics
| Characteristic | USL261 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 29 Participants | 58 Participants |
| Age, Continuous | 32.7 years STANDARD_DEVIATION 12.94 | 35.9 years STANDARD_DEVIATION 13.56 | 34.3 years STANDARD_DEVIATION 13.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 29 Participants | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 26 Participants | 27 Participants | 53 Participants |
| Region of Enrollment Belgium | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Czechia | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Germany | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Lithuania | 3 participants | 2 participants | 5 participants |
| Region of Enrollment Spain | 3 participants | 4 participants | 7 participants |
| Region of Enrollment United States | 22 participants | 22 participants | 44 participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 39 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 16 / 31 | 17 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 |
Outcome results
Primary
Number of Participants That Were Seizure-free
A participant was considered seizure-free if he or she completed the 6-hour Treatment Phase without seizures recorded, premature discontinuation of study drug, rescue intervention for acute central respiratory depression adverse event (AE), and alterations to background anti-epileptic drug (AED) therapy. Otherwise, the participant was included in the analysis for seizure-free events with the outcome of seizure.
Time frame: 6 hours
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| USL261 | Number of Participants That Were Seizure-free | 17 Participants |
| Placebo | Number of Participants That Were Seizure-free | 12 Participants |
Comparison: Assumptions included that the proportion of seizures occurring within 6 hours after placebo administration was \~65% and a relative reduction of 50% would result in a reduction of ≥ 32.5 percentage points. Based on a 2-sided 95% confidence interval (CI) for the differences in proportions, a sample size of 62 analyzable subjects was chosen to detect a 0.35 difference between group. Sample size estimations were based on nQuery Version 7.0 using the table for CIs for differences in 2 proportions.p-value: 0.1972Wald asymptotic
Secondary
Time to First Seizure Following Treatment (TFSFT)
Time to first seizure following treatment was defined as time from treatment with study drug to the onset of the next seizure, rescue intervention (for acute central respiratory depression AE) to maintain subject safety, alterations to background AED therapy, early termination, or 6 hours, whichever came first.
Time frame: 6 hours
Population: Intent-to-treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| USL261 | Time to First Seizure Following Treatment (TFSFT) | NA hours |
| Placebo | Time to First Seizure Following Treatment (TFSFT) | 3.9 hours |
p-value: 0.1388Log Rank