Brief Summary
The purpose of this study is to examine the safety and effectiveness of USL261 for the outpatient treatment of seizure clusters.
Brief Title
Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters
Detailed Description
Qualifying participants underwent an in-clinic administration (Test Dose Phase \[TDP\]) of two doses of USL261 (intranasal midazolam 5 mg), separated by 10 minutes, in the absence of seizures. Eligible participants were then randomized to USL261 versus Placebo in an outpatient Comparative Phase (CP). When the participant had a qualifying seizure cluster episode, as described in an individualized patient management plan, the participant's caregiver administered the double-blind dose. An open-label USL261 dose could be administered after 10 minutes and up to 6 hours after the double-blind dose, if the participant had persistent or recurrent seizures. Initial participants could not proceed to CP until an independent data safety monitoring board (DSMB) reviewed safety data from at least the first 25 participants in TDP; the DSMB performed additional safety reviews at pre-set intervals based on enrollment.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Epilepsy
Eligibility Criteria
Inclusion Criteria:
* Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes
* Has an established diagnosis of partial or generalized epilepsy that includes the following:
* A documented history of seizure clusters lasting a minimum of 10 minutes
* Seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure activity (if any)
* A second seizure in the seizure cluster typically occurring within 6 hours from the time of cluster recognition
* A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures
* A seizure cluster pattern established \> 3 months before Visit 1
* A frequency of ≥ 3 seizure clusters during the year before Visit 1
* At least 1 seizure cluster occurring ≤ 4 months before Visit 1
* Seizure cluster pattern is confirmed by a central reviewer
* Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
* Weight is 40 kg to 125 kg, inclusive
Exclusion Criteria:
* Has a neurological disorder that is likely to progress in the next year
* Has severe chronic cardio-respiratory disease
* Has had psychogenic, non-epileptic seizure(s) within the 5 years before Visit 1
* Has a history of their stereotypical seizure cluster progressing to status epilepticus within the 2 years before Visit 1
* Has a history of acute narrow-angle glaucoma.
* Has had active suicidal plan/intent or active suicidal thoughts in the 6 months before Visit 1 or a suicide attempt in the past 5 years
* Currently using a vagal nerve stimulator (VNS) unless the device has been implanted for at least 6 months and the setting stable for 4 weeks before Visit 1
* Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes
* Has an established diagnosis of partial or generalized epilepsy that includes the following:
* A documented history of seizure clusters lasting a minimum of 10 minutes
* Seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure activity (if any)
* A second seizure in the seizure cluster typically occurring within 6 hours from the time of cluster recognition
* A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures
* A seizure cluster pattern established \> 3 months before Visit 1
* A frequency of ≥ 3 seizure clusters during the year before Visit 1
* At least 1 seizure cluster occurring ≤ 4 months before Visit 1
* Seizure cluster pattern is confirmed by a central reviewer
* Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
* Weight is 40 kg to 125 kg, inclusive
Exclusion Criteria:
* Has a neurological disorder that is likely to progress in the next year
* Has severe chronic cardio-respiratory disease
* Has had psychogenic, non-epileptic seizure(s) within the 5 years before Visit 1
* Has a history of their stereotypical seizure cluster progressing to status epilepticus within the 2 years before Visit 1
* Has a history of acute narrow-angle glaucoma.
* Has had active suicidal plan/intent or active suicidal thoughts in the 6 months before Visit 1 or a suicide attempt in the past 5 years
* Currently using a vagal nerve stimulator (VNS) unless the device has been implanted for at least 6 months and the setting stable for 4 weeks before Visit 1
Inclusion Criteria
Inclusion Criteria:
* Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes
* Has an established diagnosis of partial or generalized epilepsy that includes the following:
* A documented history of seizure clusters lasting a minimum of 10 minutes
* Seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure activity (if any)
* A second seizure in the seizure cluster typically occurring within 6 hours from the time of cluster recognition
* A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures
* A seizure cluster pattern established \> 3 months before Visit 1
* A frequency of ≥ 3 seizure clusters during the year before Visit 1
* At least 1 seizure cluster occurring ≤ 4 months before Visit 1
* Seizure cluster pattern is confirmed by a central reviewer
* Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
* Weight is 40 kg to 125 kg, inclusive
* Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes
* Has an established diagnosis of partial or generalized epilepsy that includes the following:
* A documented history of seizure clusters lasting a minimum of 10 minutes
* Seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure activity (if any)
* A second seizure in the seizure cluster typically occurring within 6 hours from the time of cluster recognition
* A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures
* A seizure cluster pattern established \> 3 months before Visit 1
* A frequency of ≥ 3 seizure clusters during the year before Visit 1
* At least 1 seizure cluster occurring ≤ 4 months before Visit 1
* Seizure cluster pattern is confirmed by a central reviewer
* Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
* Weight is 40 kg to 125 kg, inclusive
Gender
All
Gender Based
false
Keywords
Epilepsy
seizure clusters
acute repetitive seizures
rescue treatment
ARTEMIS
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT01390220
Org Class
Industry
Org Full Name
UCB Pharma
Org Study Id
P261-401
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Intranasal Midazolam (USL261) in the Outpatient Treatment of Subjects With Seizure Clusters. ARTEMIS-1: Acute Rescue Therapy in Epilepsy With Midazolam Intranasal Spray-1
Primary Outcomes
Outcome Description
Treatment Success is defined as achieving both of the following: 1) termination of seizure(s) within 10 minutes after double-blind study drug administration, and 2) no recurrence of seizure(s) beginning 10 minutes after study drug administration to 6 hours after study drug administration. Participants who received the open-label second dose within 6 hours of administration of the double-blind dose were analyzed as having had a seizure.
Outcome Measure
Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
Outcome Time Frame
6 hours
Secondary Ids
Secondary Id
2011-001318-32
Secondary Outcomes
Outcome Description
Participants with recurrence of seizure(s) \>10 minutes and up to 4 hours after administration of the double-blind dose in the CP. Participants who received the open-label second dose within 4 hours of administration of the double-blind dose were analyzed as having had a seizure.
Outcome Time Frame
4 hours
Outcome Measure
Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
Outcome Description
Occurrence of next seizure with a start time \>10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration.
Outcome Time Frame
24 hours
Outcome Measure
Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Outcome Description
Time to next seizure with a start time \>10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration.
Outcome Time Frame
24 hours
Outcome Measure
Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alexis Boro
Investigator Email
aboro@montefiore.org
Investigator Phone