Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters

Epilepsy Clinical Trial

— ARTEMIS1  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01390220
• Other study ID #: P261-401
• Secondary ID: 2011-001318-32
• Status: Terminated
• Phase: Phase 3
• Start date: June 2011
• Est. completion date: March 2017

Study information

• Verified date: October 2019
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the safety and effectiveness of USL261 for the outpatient treatment of seizure clusters.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 292
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• USL261

• Placebo

Locations

Country	Name	City	State
Australia	Australia, New South Wales	Chatswood	New South Wales
Australia	Australia, Vctoria	Heidelberg West	Victoria
Australia	Australia, Queensland	Herston	Queensland
Australia	Australia, Victoria	Parkville	Victoria
Australia	Australia, New South Wales	Randwick	New South Wales
Canada	Canada, Quebec	Montreal	Quebec
Canada	Canada, Ontario	Toronto	Ontario
Germany	Germany, Westfalen-Lippe	Bielefeld	Wetsfalen-Lippe
Germany	Germany, Nordrhein-Westfalen	Bonn	Nordrhein-Westfalen
Germany	Germany, Baden-Wurttemberg	Freiburg	Baden-Wurttemberg
Germany	Germany, Hessen	Marburg	Hessen
Germany	Germany, Bayern	Munich	Bayern
Hungary	Hungary	Budapest
Hungary	Hungary	Kazincbarcika
Israel	Israel	Haifa
Israel	Israel	Holon
Israel	Israel	Jerusalem
Israel	Israel	Petach Tikva
Israel	Israel	Ramat Gan
Israel	Israel	Tel Aviv
Italy	Italy	Firenze
Italy	Italy	Genova
Italy	Italy	Milano
Italy	Italy	Napoli
Italy	Italy	Pavia
Italy	Italy	San Fermo della Battaglia
New Zealand	New Zealand, Canterbury	Christchurch	Canterbury
New Zealand	New Zealand, Auklund	Grafton	Auklund
Poland	Poland	Gdansk
Poland	Poland	Katowice
Poland	Poland	Krakow
Poland	Poland	Olsztyn
Spain	Spain, Catalonia	Barcelona	Catalonia
Spain	Spain, Madrid	Fuencarral-El Pardo	Madrid
Spain	Spain, Catalonia	Girona	Catalonia
Spain	Spain, Madrid	Moncloa-Aravaca	Madrid
Spain	Spain, Madrid	Pozuelo De Alarcón	Madrid
Spain	Spain, Andalucia	Sevilla	Andalucia
Ukraine	Ukraine, Ivano-Frankivsk	Ivano-Frankivsk
Ukraine	Ukraine	Kharkiv
Ukraine	Ukraine	Odessa
Ukraine	Ukraine	Poltava
Ukraine	Ukraine	Ternopil
Ukraine	Ukraine	Vinnytsya
United States	United States, Colorado	Aurora	Colorado
United States	United States, Maryland	Baltimore	Maryland
United States	United States, Idaho	Boise	Idaho
United States	United States, New York	Bronx	New York
United States	United States, Missouri	Chesterfield	Missouri
United States	United States, Illinois	Chicago	Illinois
United States	United States, Ohio	Columbus	Ohio
United States	United States, Texas	Dallas	Texas
United States	United States, Michigan	Detroit	Michigan
United States	United States, North Carolina	Durham	North Carolina
United States	United States, New Jersey	Flemington	New Jersey
United States	United States, Texas	Fort Worth	Texas
United States	United States, California	Fresno	California
United States	United States, Florida	Gainesville	Florida
United States	United States, Texas	Greenville	Texas
United States	United States, Florida	Gulf Breeze	Florida
United States	United States, New Jersey	Hackensack	New Jersey
United States	United States, California	Irvine	California
United States	United States, New Hampshire	Lebanon	New Hampshire
United States	United States, Kentucky	Lexington	Kentucky
United States	United States, Arkansas	Little Rock	Arkansas
United States	United States, California	Loma Linda	California
United States	United States, Wisconsin	Madison	Wisconsin
United States	United States, Kansas	Manhattan	Kansas
United States	United States, Tennessee	Memphis	Tennessee
United States	United States, Tennessee	Nashville	Tennessee
United States	United States, Connecticut	New Haven	Connecticut
United States	United States, New York	New York	New York
United States	United States, Virginia	Norfolk	Virginia
United States	United States, Oklahoma	Oklahoma City	Oklahoma
United States	United States, Pennsylvania	Philadelphia	Pennsylvania
United States	United States, Arizona	Phoenix	Arizona
United States	United States, Florida	Port Charlotte	Florida
United States	United States, Oregon	Portland	Oregon
United States	United States, Nevada	Reno	Nevada
United States	United States, California	Sacramento	California
United States	United States, Missouri	Saint Louis	Missouri
United States	United States, Minnesota	Saint Paul	Minnesota
United States	United States, Texas	San Antonio	Texas
United States	United States, New York	Stony Brook	New York
United States	United States, Florida	Tampa	Florida
United States	United States, Texas	Temple	Texas
United States	United States, Arizona	Tucson	Arizona
United States	United States, California	Ventura	California
United States	United States, Florida	Wellington	Florida
United States	United States, North Carolina	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma S.P.R.L.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Hungary,  Israel,  Italy,  New Zealand,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)	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.	6 hours
Secondary	Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose	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.	4 hours
Secondary	Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose	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.	24 hours
Secondary	Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose	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.	24 hours