Clinical trial NCT01390220: Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Epilepsy
seizure clusters
acute repetitive seizures
rescue treatment
ARTEMIS
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2011-07-08
Enrollment: 292
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the safety and effectiveness of USL261 for the outpatient treatment of 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.

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

Primary outcomes:
measure: Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
timeFrame: 6 hours
Secondary outcomes:
measure: Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
timeFrame: 4 hours
measure: Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
timeFrame: 24 hours
measure: Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
timeFrame: 24 hours
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: United States, Arizona
state: Arizona
city: Tucson
country: United States
facility: United States, Arizona
state: Arizona
city: Little Rock
country: United States
facility: United States, Arkansas
state: Arkansas
city: Fresno
country: United States
facility: United States, California
state: California
city: Irvine
country: United States
facility: United States, California
state: California
city: Loma Linda
country: United States
facility: United States, California
state: California
city: Sacramento
country: United States
facility: United States, California
state: California
city: Ventura
country: United States
facility: United States, California
state: California
city: Aurora
country: United States
facility: United States, Colorado
state: Colorado
city: New Haven
country: United States
facility: United States, Connecticut
state: Connecticut
city: Gainesville
country: United States
facility: United States, Florida
state: Florida
city: Gulf Breeze
country: United States
facility: United States, Florida
state: Florida
city: Port Charlotte
country: United States
facility: United States, Florida
state: Florida
city: Tampa
country: United States
facility: United States, Florida
state: Florida
city: Wellington
country: United States
facility: United States, Florida
state: Florida
city: Boise
country: United States
facility: United States, Idaho
state: Idaho
city: Chicago
country: United States
facility: United States, Illinois
state: Illinois
city: Manhattan
country: United States
facility: United States, Kansas
state: Kansas
city: Lexington
country: United States
facility: United States, Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: United States, Maryland
state: Maryland
city: Detroit
country: United States
facility: United States, Michigan
state: Michigan
city: Saint Paul
country: United States
facility: United States, Minnesota
state: Minnesota
city: Chesterfield
country: United States
facility: United States, Missouri
state: Missouri
city: Saint Louis
country: United States
facility: United States, Missouri
state: Missouri
city: Reno
country: United States
facility: United States, Nevada
state: Nevada
city: Lebanon
country: United States
facility: United States, New Hampshire
state: New Hampshire
city: Flemington
country: United States
facility: United States, New Jersey
state: New Jersey
city: Hackensack
country: United States
facility: United States, New Jersey
state: New Jersey
city: Bronx
country: United States
facility: United States, New York
state: New York
city: New York
country: United States
facility: United States, New York
state: New York
city: Stony Brook
country: United States
facility: United States, New York
state: New York
city: Durham
country: United States
facility: United States, North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: United States, North Carolina
state: North Carolina
city: Columbus
country: United States
facility: United States, Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: United States, Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: United States, Oregon
state: Oregon
city: Philadelphia
country: United States
facility: United States, Pennsylvania
state: Pennsylvania
city: Memphis
country: United States
facility: United States, Tennessee
state: Tennessee
city: Nashville
country: United States
facility: United States, Tennessee
state: Tennessee
city: Dallas
country: United States
facility: United States, Texas
state: Texas
city: Fort Worth
country: United States
facility: United States, Texas
state: Texas
city: Greenville
country: United States
facility: United States, Texas
state: Texas
city: San Antonio
country: United States
facility: United States, Texas
state: Texas
city: Temple
country: United States
facility: United States, Texas
state: Texas
city: Norfolk
country: United States
facility: United States, Virginia
state: Virginia
city: Madison
country: United States
facility: United States, Wisconsin
state: Wisconsin
city: Chatswood
country: Australia
facility: Australia, New South Wales
state: New South Wales
city: Randwick
country: Australia
facility: Australia, New South Wales
state: New South Wales
city: Herston
country: Australia
facility: Australia, Queensland
state: Queensland
city: Heidelberg West
country: Australia
facility: Australia, Vctoria
state: Victoria
city: Parkville
country: Australia
facility: Australia, Victoria
state: Victoria
city: Toronto
country: Canada
facility: Canada, Ontario
state: Ontario
city: Montreal
country: Canada
facility: Canada, Quebec
state: Quebec
city: Freiburg
country: Germany
facility: Germany, Baden-Wurttemberg
state: Baden-Wurttemberg
city: Munich
country: Germany
facility: Germany, Bayern
state: Bayern
city: Marburg
country: Germany
facility: Germany, Hessen
state: Hessen
city: Bonn
country: Germany
facility: Germany, Nordrhein-Westfalen
state: Nordrhein-Westfalen
city: Bielefeld
country: Germany
facility: Germany, Westfalen-Lippe
state: Wetsfalen-Lippe
city: Budapest
country: Hungary
facility: Hungary
city: Kazincbarcika
country: Hungary
facility: Hungary
city: Haifa
country: Israel
facility: Israel
city: Holon
country: Israel
facility: Israel
city: Jerusalem
country: Israel
facility: Israel
city: Petach Tikva
country: Israel
facility: Israel
city: Ramat Gan
country: Israel
facility: Israel
city: Tel Aviv
country: Israel
facility: Israel
city: Firenze
country: Italy
facility: Italy
city: Genova
country: Italy
facility: Italy
city: Milano
country: Italy
facility: Italy
city: Napoli
country: Italy
facility: Italy
city: Pavia
country: Italy
facility: Italy
city: San Fermo della Battaglia
country: Italy
facility: Italy
city: Grafton
country: New Zealand
facility: New Zealand, Auklund
state: Auklund
city: Christchurch
country: New Zealand
facility: New Zealand, Canterbury
state: Canterbury
city: Gdansk
country: Poland
facility: Poland
city: Katowice
country: Poland
facility: Poland
city: Krakow
country: Poland
facility: Poland
city: Olsztyn
country: Poland
facility: Poland
city: Sevilla
country: Spain
facility: Spain, Andalucia
state: Andalucia
city: Barcelona
country: Spain
facility: Spain, Catalonia
state: Catalonia
city: Girona
country: Spain
facility: Spain, Catalonia
state: Catalonia
city: Fuencarral-El Pardo
country: Spain
facility: Spain, Madrid
state: Madrid
city: Moncloa-Aravaca
country: Spain
facility: Spain, Madrid
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Spain, Madrid
state: Madrid
city: Ivano-Frankivsk
country: Ukraine
facility: Ukraine, Ivano-Frankivsk
city: Kharkiv
country: Ukraine
facility: Ukraine
city: Odessa
country: Ukraine
facility: Ukraine
city: Poltava
country: Ukraine
facility: Ukraine
city: Ternopil
country: Ukraine
facility: Ukraine
city: Vinnytsya
country: Ukraine
facility: Ukraine
Study officials:
References:
citation: Detyniecki K, Van Ess PJ, Sequeira DJ, Wheless JW, Meng TC, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters-a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019 Sep;60(9):1797-1808. doi: 10.1111/epi.15159. Epub 2019 May 29.