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Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters (ARTEMIS1)

Primary Purpose

Epilepsy

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
USL261
Placebo
Sponsored by
UCB Biopharma S.P.R.L.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment, ARTEMIS

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • United States, Arizona
  • United States, Arizona
  • United States, Arkansas
  • United States, California
  • United States, California
  • United States, California
  • United States, California
  • United States, California
  • United States, Colorado
  • United States, Connecticut
  • United States, Florida
  • United States, Florida
  • United States, Florida
  • United States, Florida
  • United States, Florida
  • United States, Idaho
  • United States, Illinois
  • United States, Kansas
  • United States, Kentucky
  • United States, Maryland
  • United States, Michigan
  • United States, Minnesota
  • United States, Missouri
  • United States, Missouri
  • United States, Nevada
  • United States, New Hampshire
  • United States, New Jersey
  • United States, New Jersey
  • United States, New York
  • United States, New York
  • United States, New York
  • United States, North Carolina
  • United States, North Carolina
  • United States, Ohio
  • United States, Oklahoma
  • United States, Oregon
  • United States, Pennsylvania
  • United States, Tennessee
  • United States, Tennessee
  • United States, Texas
  • United States, Texas
  • United States, Texas
  • United States, Texas
  • United States, Texas
  • United States, Virginia
  • United States, Wisconsin
  • Australia, New South Wales
  • Australia, New South Wales
  • Australia, Queensland
  • Australia, Vctoria
  • Australia, Victoria
  • Canada, Ontario
  • Canada, Quebec
  • Germany, Baden-Wurttemberg
  • Germany, Bayern
  • Germany, Hessen
  • Germany, Nordrhein-Westfalen
  • Germany, Westfalen-Lippe
  • Hungary
  • Hungary
  • Israel
  • Israel
  • Israel
  • Israel
  • Israel
  • Israel
  • Italy
  • Italy
  • Italy
  • Italy
  • Italy
  • Italy
  • New Zealand, Auklund
  • New Zealand, Canterbury
  • Poland
  • Poland
  • Poland
  • Poland
  • Spain, Andalucia
  • Spain, Catalonia
  • Spain, Catalonia
  • Spain, Madrid
  • Spain, Madrid
  • Spain, Madrid
  • Ukraine, Ivano-Frankivsk
  • Ukraine
  • Ukraine
  • Ukraine
  • Ukraine
  • Ukraine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

USL261

Placebo

Arm Description

intranasal midazolam 5mg

Intranasal placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
July 6, 2011
Last Updated
October 8, 2019
Sponsor
UCB Biopharma S.P.R.L.
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1. Study Identification

Unique Protocol Identification Number
NCT01390220
Brief Title
Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Terminated
Study Start Date
June 2011 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Biopharma S.P.R.L.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment, ARTEMIS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
292 (Actual)

8. Arms, Groups, and Interventions

Arm Title
USL261
Arm Type
Experimental
Arm Description
intranasal midazolam 5mg
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Intranasal placebo
Intervention Type
Drug
Intervention Name(s)
USL261
Other Intervention Name(s)
Midazolam nasal spray (MDZ NS)
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
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.
Time Frame
6 hours
Secondary Outcome Measure Information:
Title
Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
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.
Time Frame
4 hours
Title
Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
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.
Time Frame
24 hours
Title
Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
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.
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
United States, Arizona
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
United States, Arizona
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
United States, Arkansas
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
United States, California
City
Fresno
State/Province
California
Country
United States
Facility Name
United States, California
City
Irvine
State/Province
California
Country
United States
Facility Name
United States, California
City
Loma Linda
State/Province
California
Country
United States
Facility Name
United States, California
City
Sacramento
State/Province
California
Country
United States
Facility Name
United States, California
City
Ventura
State/Province
California
Country
United States
Facility Name
United States, Colorado
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
United States, Connecticut
City
New Haven
State/Province
Connecticut
Country
United States
Facility Name
United States, Florida
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
United States, Florida
City
Gulf Breeze
State/Province
Florida
Country
United States
Facility Name
United States, Florida
City
Port Charlotte
State/Province
Florida
Country
United States
Facility Name
United States, Florida
City
Tampa
State/Province
Florida
Country
United States
Facility Name
United States, Florida
City
Wellington
State/Province
Florida
Country
United States
Facility Name
United States, Idaho
City
Boise
State/Province
Idaho
Country
United States
Facility Name
United States, Illinois
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
United States, Kansas
City
Manhattan
State/Province
Kansas
Country
United States
Facility Name
United States, Kentucky
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
United States, Maryland
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
United States, Michigan
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
United States, Minnesota
City
Saint Paul
State/Province
Minnesota
Country
United States
Facility Name
United States, Missouri
City
Chesterfield
State/Province
Missouri
Country
United States
Facility Name
United States, Missouri
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
United States, Nevada
City
Reno
State/Province
Nevada
Country
United States
Facility Name
United States, New Hampshire
City
Lebanon
State/Province
New Hampshire
Country
United States
Facility Name
United States, New Jersey
City
Flemington
State/Province
New Jersey
Country
United States
Facility Name
United States, New Jersey
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
United States, New York
City
Bronx
State/Province
New York
Country
United States
Facility Name
United States, New York
City
New York
State/Province
New York
Country
United States
Facility Name
United States, New York
City
Stony Brook
State/Province
New York
Country
United States
Facility Name
United States, North Carolina
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
United States, North Carolina
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
United States, Ohio
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
United States, Oklahoma
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
United States, Oregon
City
Portland
State/Province
Oregon
Country
United States
Facility Name
United States, Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
United States, Tennessee
City
Memphis
State/Province
Tennessee
Country
United States
Facility Name
United States, Tennessee
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
United States, Texas
City
Dallas
State/Province
Texas
Country
United States
Facility Name
United States, Texas
City
Fort Worth
State/Province
Texas
Country
United States
Facility Name
United States, Texas
City
Greenville
State/Province
Texas
Country
United States
Facility Name
United States, Texas
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
United States, Texas
City
Temple
State/Province
Texas
Country
United States
Facility Name
United States, Virginia
City
Norfolk
State/Province
Virginia
Country
United States
Facility Name
United States, Wisconsin
City
Madison
State/Province
Wisconsin
Country
United States
Facility Name
Australia, New South Wales
City
Chatswood
State/Province
New South Wales
Country
Australia
Facility Name
Australia, New South Wales
City
Randwick
State/Province
New South Wales
Country
Australia
Facility Name
Australia, Queensland
City
Herston
State/Province
Queensland
Country
Australia
Facility Name
Australia, Vctoria
City
Heidelberg West
State/Province
Victoria
Country
Australia
Facility Name
Australia, Victoria
City
Parkville
State/Province
Victoria
Country
Australia
Facility Name
Canada, Ontario
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Canada, Quebec
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Germany, Baden-Wurttemberg
City
Freiburg
State/Province
Baden-Wurttemberg
Country
Germany
Facility Name
Germany, Bayern
City
Munich
State/Province
Bayern
Country
Germany
Facility Name
Germany, Hessen
City
Marburg
State/Province
Hessen
Country
Germany
Facility Name
Germany, Nordrhein-Westfalen
City
Bonn
State/Province
Nordrhein-Westfalen
Country
Germany
Facility Name
Germany, Westfalen-Lippe
City
Bielefeld
State/Province
Wetsfalen-Lippe
Country
Germany
Facility Name
Hungary
City
Budapest
Country
Hungary
Facility Name
Hungary
City
Kazincbarcika
Country
Hungary
Facility Name
Israel
City
Haifa
Country
Israel
Facility Name
Israel
City
Holon
Country
Israel
Facility Name
Israel
City
Jerusalem
Country
Israel
Facility Name
Israel
City
Petach Tikva
Country
Israel
Facility Name
Israel
City
Ramat Gan
Country
Israel
Facility Name
Israel
City
Tel Aviv
Country
Israel
Facility Name
Italy
City
Firenze
Country
Italy
Facility Name
Italy
City
Genova
Country
Italy
Facility Name
Italy
City
Milano
Country
Italy
Facility Name
Italy
City
Napoli
Country
Italy
Facility Name
Italy
City
Pavia
Country
Italy
Facility Name
Italy
City
San Fermo della Battaglia
Country
Italy
Facility Name
New Zealand, Auklund
City
Grafton
State/Province
Auklund
Country
New Zealand
Facility Name
New Zealand, Canterbury
City
Christchurch
State/Province
Canterbury
Country
New Zealand
Facility Name
Poland
City
Gdansk
Country
Poland
Facility Name
Poland
City
Katowice
Country
Poland
Facility Name
Poland
City
Krakow
Country
Poland
Facility Name
Poland
City
Olsztyn
Country
Poland
Facility Name
Spain, Andalucia
City
Sevilla
State/Province
Andalucia
Country
Spain
Facility Name
Spain, Catalonia
City
Barcelona
State/Province
Catalonia
Country
Spain
Facility Name
Spain, Catalonia
City
Girona
State/Province
Catalonia
Country
Spain
Facility Name
Spain, Madrid
City
Fuencarral-El Pardo
State/Province
Madrid
Country
Spain
Facility Name
Spain, Madrid
City
Moncloa-Aravaca
State/Province
Madrid
Country
Spain
Facility Name
Spain, Madrid
City
Pozuelo De Alarcón
State/Province
Madrid
Country
Spain
Facility Name
Ukraine, Ivano-Frankivsk
City
Ivano-Frankivsk
Country
Ukraine
Facility Name
Ukraine
City
Kharkiv
Country
Ukraine
Facility Name
Ukraine
City
Odessa
Country
Ukraine
Facility Name
Ukraine
City
Poltava
Country
Ukraine
Facility Name
Ukraine
City
Ternopil
Country
Ukraine
Facility Name
Ukraine
City
Vinnytsya
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31140596
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.
Results Reference
derived

Learn more about this trial

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

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