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Study to Evaluate the Long-term Safety and Tolerability of USL261 in Patients With Seizure Clusters

Primary Purpose

Epilepsy

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
USL261
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

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 successfully completed study P261-401, and the subject and caregiver have demonstrated adequate compliance with P261-401 study procedures as determined by the investigator

Exclusion Criteria:

  • Has experienced status epilepticus during or since the P261-401 study
  • In the opinion of the investigator, is experiencing an ongoing, uncontrolled, clinically significant adverse event(s) from P261-401 at Visit 1 or did experience a clinically significant adverse event in study P261-401 that might prevent the subject from safely participating in the study
  • Has a neurological disorder that is likely to progress in the next year
  • Has a history of acute narrow-angle glaucoma
  • Has a medical condition including uncontrolled cardiac, pulmonary, renal, hepatic, or gastrointestinal disease that could interfere with the study, subject safety/safety monitoring, or is not stable despite current therapy
  • Subject has severe chronic cardio-respiratory disease or the need for ambulatory oxygen
  • Has had psychogenic, non-epileptic seizure(s) during or since the P261-401 study
  • Has active suicidal plan or intent as determined by the C-SSRS at Visit 1 or medical history
  • Subject has had vagus nerve stimulator (VNS) implanted since the completion of study P261-401

Sites / Locations

  • United States, Arizona
  • United States, Arizona
  • United States, Arizona
  • United States, Arkansas
  • United States, California
  • United States, California
  • United States, California
  • United States, Colorado
  • United States, Connecticut
  • United States, Florida
  • United States, Florida
  • United States, Idaho
  • United States, Illinois
  • United States, Kentucky
  • United States, Maryland
  • United States, Michigan
  • United States, Minnesota
  • United States, Missouri
  • United States, New Hampshire
  • 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, Oklahoma
  • United States, Pennsylvania
  • United States, Tennessee
  • United States, Tennessee
  • United States, Texas
  • United States, Texas
  • Australia, New South Wales
  • Australia, Victoria
  • Australia, Victoria
  • Canada
  • Canada, Toronto
  • Canada
  • Germany
  • Germany
  • Germany
  • Germany
  • Hungary
  • Israel
  • Israel
  • Israel
  • New Zealand
  • Poland
  • Poland
  • Poland
  • Spain
  • Spain
  • Spain
  • Ukraine
  • Ukraine
  • Ukraine
  • Ukraine
  • Ukraine
  • Ukraine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

USL261

Arm Description

Intranasal midazolam 5 mg

Outcomes

Primary Outcome Measures

Duration of Safety Observation
Duration of participant study participation for collection of long term safety data
Participants Meeting Predefined Safety Criteria for Vital Signs
Participants meeting predefined safety criteria for vital signs (systolic blood pressure [SBP] <85 mm Hg, SBP change from baseline >/= 40 mm Hg, diastolic BP [DBP] <50 mm Hg, DBP change from baseline >/=30 mm Hg, pulse rate <50 beats per minute (bpm), pulse rate >120 bpm, pulse rate change >/= 40 bpm at any visit post baseline or for caregiver recorded participant respiration rate [RR] <8 breaths per minute (brpm) or >24 brpm) after any USL261 treated seizure cluster episode. Abnormal vital signs were assessed separately by investigator and recorded as adverse events if applicable.
Participants With Laboratory Abnormalities Meeting Predefined Criteria
Participants with abnormal laboratory finding, at any time post baseline, meeting predefined criteria. Abnormal laboratory findings were assessed separately by investigator and recorded as adverse events if applicable. Alanine aminotransferase (ALT); Alkaline phosphatase (ALP); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); upper limit of normal (ULN)
Participants With Clinically Significant Abnormalities Physical Examination
Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.
Participants With Clinically Significant Abnormalities on Neurologic Examination
Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator
Participants With Clinically Significant Abnormalities on Nasal Examination
Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
Participant Change in B-SIT Score
Change in participant Brief Smell Identification Test (B-SIT) score from baseline to last visit with assessment. The B-SIT is a self-administered 12-item test; the score indicates odors correctly identified (0 to 12). The B-SIT was added while the study was already ongoing (Protocol Amendment 4, 20 May 2015) in response to a regulatory request. The test was only implemented at sites in the United States and included only participants considered by the investigator to have adequate cognitive ability to perform the test. Baseline was defined as the latest non-missing value prior to administration of USL261 in the Test Dose Phase of Study P261-401.
Participants With Suicidal Ideation
Participants with suicidal ideation reported on Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at any post-baseline visit. Responses including: Wish to be Dead; Non-Specific Active Suicidal Thoughts; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent; and Any Suicidal Ideation Regardless of Type.
Emergency Room/Emergency Medical Service Visits
Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)

Secondary Outcome Measures

Number of Treated Seizure Clusters Meeting Criteria for Treatment Success
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success: Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after administration of first dose of USL261 (intranasal midazolam 5 mg)

Full Information

First Posted
February 3, 2012
Last Updated
January 19, 2023
Sponsor
UCB Biopharma S.P.R.L.
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1. Study Identification

Unique Protocol Identification Number
NCT01529034
Brief Title
Study to Evaluate the Long-term Safety and Tolerability of USL261 in Patients With Seizure Clusters
Official Title
An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Study Start Date
July 2012 (Actual)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters.
Detailed Description
Participants who completed study P261-401 (NCT01390220), a randomized double-blind study of USL261 (intranasal midazolam) versus placebo to acutely treat a seizure cluster episode, were eligible to to enroll in this open-label extension study (P261-402). The participant's caregiver administered a USL261 5 milligram (mg) dose for a seizure episode meeting study criteria. A second USL261 5 mg dose could be administered after 10 minutes and up to 6 hours after the first dose for persistent or recurrent seizures, unless the participant met exclusions to administration of the second dose. A participant could have more than 1 seizure cluster episode treated during his/her study participation.

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
175 (Actual)

8. Arms, Groups, and Interventions

Arm Title
USL261
Arm Type
Experimental
Arm Description
Intranasal midazolam 5 mg
Intervention Type
Drug
Intervention Name(s)
USL261
Primary Outcome Measure Information:
Title
Duration of Safety Observation
Description
Duration of participant study participation for collection of long term safety data
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participants Meeting Predefined Safety Criteria for Vital Signs
Description
Participants meeting predefined safety criteria for vital signs (systolic blood pressure [SBP] <85 mm Hg, SBP change from baseline >/= 40 mm Hg, diastolic BP [DBP] <50 mm Hg, DBP change from baseline >/=30 mm Hg, pulse rate <50 beats per minute (bpm), pulse rate >120 bpm, pulse rate change >/= 40 bpm at any visit post baseline or for caregiver recorded participant respiration rate [RR] <8 breaths per minute (brpm) or >24 brpm) after any USL261 treated seizure cluster episode. Abnormal vital signs were assessed separately by investigator and recorded as adverse events if applicable.
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participants With Laboratory Abnormalities Meeting Predefined Criteria
Description
Participants with abnormal laboratory finding, at any time post baseline, meeting predefined criteria. Abnormal laboratory findings were assessed separately by investigator and recorded as adverse events if applicable. Alanine aminotransferase (ALT); Alkaline phosphatase (ALP); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); upper limit of normal (ULN)
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participants With Clinically Significant Abnormalities Physical Examination
Description
Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participants With Clinically Significant Abnormalities on Neurologic Examination
Description
Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participants With Clinically Significant Abnormalities on Nasal Examination
Description
Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participant Change in B-SIT Score
Description
Change in participant Brief Smell Identification Test (B-SIT) score from baseline to last visit with assessment. The B-SIT is a self-administered 12-item test; the score indicates odors correctly identified (0 to 12). The B-SIT was added while the study was already ongoing (Protocol Amendment 4, 20 May 2015) in response to a regulatory request. The test was only implemented at sites in the United States and included only participants considered by the investigator to have adequate cognitive ability to perform the test. Baseline was defined as the latest non-missing value prior to administration of USL261 in the Test Dose Phase of Study P261-401.
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Participants With Suicidal Ideation
Description
Participants with suicidal ideation reported on Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at any post-baseline visit. Responses including: Wish to be Dead; Non-Specific Active Suicidal Thoughts; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent; and Any Suicidal Ideation Regardless of Type.
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Title
Emergency Room/Emergency Medical Service Visits
Description
Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)
Time Frame
From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Secondary Outcome Measure Information:
Title
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success
Description
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success: Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after administration of first dose of USL261 (intranasal midazolam 5 mg)
Time Frame
6 hours after first dose of USL261 for each treated seizure cluster

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 successfully completed study P261-401, and the subject and caregiver have demonstrated adequate compliance with P261-401 study procedures as determined by the investigator Exclusion Criteria: Has experienced status epilepticus during or since the P261-401 study In the opinion of the investigator, is experiencing an ongoing, uncontrolled, clinically significant adverse event(s) from P261-401 at Visit 1 or did experience a clinically significant adverse event in study P261-401 that might prevent the subject from safely participating in the study Has a neurological disorder that is likely to progress in the next year Has a history of acute narrow-angle glaucoma Has a medical condition including uncontrolled cardiac, pulmonary, renal, hepatic, or gastrointestinal disease that could interfere with the study, subject safety/safety monitoring, or is not stable despite current therapy Subject has severe chronic cardio-respiratory disease or the need for ambulatory oxygen Has had psychogenic, non-epileptic seizure(s) during or since the P261-401 study Has active suicidal plan or intent as determined by the C-SSRS at Visit 1 or medical history Subject has had vagus nerve stimulator (VNS) implanted since the completion of study P261-401
Facility Information:
Facility Name
United States, Arizona
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
United States, Arizona
City
Scottsdale
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
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
Port Charlotte
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, 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
Saint Louis
State/Province
Missouri
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
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, Oklahoma
City
Oklahoma City
State/Province
Oklahoma
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
Greenville
State/Province
Texas
Country
United States
Facility Name
Australia, New South Wales
City
Randwick
State/Province
New South Wales
Country
Australia
Facility Name
Australia, Victoria
City
Heidelberg west
State/Province
Victoria
Country
Australia
Facility Name
Australia, Victoria
City
Parkville
State/Province
Victoria
Country
Australia
Facility Name
Canada
City
Montreal
State/Province
Ontario
Country
Canada
Facility Name
Canada, Toronto
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Canada
City
Toronto
State/Province
Quebec
Country
Canada
Facility Name
Germany
City
Munchen
State/Province
Bayern
Country
Germany
Facility Name
Germany
City
Marberg
State/Province
Hessen
Country
Germany
Facility Name
Germany
City
Bonn
State/Province
Nordrhein-Westfalen
Country
Germany
Facility Name
Germany
City
Bielefeld
State/Province
Westfalen-Lippe
Country
Germany
Facility Name
Hungary
City
Budapest
Country
Hungary
Facility Name
Israel
City
Haifa
Country
Israel
Facility Name
Israel
City
Petah Tikvah
Country
Israel
Facility Name
Israel
City
Ramat Gan
Country
Israel
Facility Name
New Zealand
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
Lublin
Country
Poland
Facility Name
Spain
City
Sevilla
State/Province
Andalucia
Country
Spain
Facility Name
Spain
City
Gerona
State/Province
Cataluyna
Country
Spain
Facility Name
Spain
City
Madrid
Country
Spain
Facility Name
Ukraine
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
Vinnytsa
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36410152
Citation
Meng TC, Szaflarski JP, Chen L, Brunnert M, Campos R, Van Ess P, Pullman WE, Fakhoury T. Psychosocial outcomes of repeated treatment of seizure clusters with midazolam nasal spray: Results of a phase 3, open-label extension trial. Epilepsy Behav. 2023 Jan;138:108989. doi: 10.1016/j.yebeh.2022.108989. Epub 2022 Nov 18.
Results Reference
result
PubMed Identifier
31353457
Citation
Wheless JW, Meng TC, Van Ess PJ, Detyniecki K, Sequeira DJ, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial. Epilepsia. 2019 Sep;60(9):1809-1819. doi: 10.1111/epi.16300. Epub 2019 Jul 29.
Results Reference
derived

Learn more about this trial

Study to Evaluate the Long-term Safety and Tolerability of USL261 in Patients With Seizure Clusters

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