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

Epilepsy Clinical Trial

Official title:

An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01529034
• Other study ID #: P261-402
• Secondary ID: 2011-004109-25
• Status: Terminated
• Phase: Phase 3
• Start date: July 2012

Study information

• Verified date: January 2023
• 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 long-term safety and tolerability of USL261 in the treatment of seizure clusters.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 175
• Est. primary completion date: April 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 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

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• USL261

Locations

Country	Name	City	State
Australia	Australia, Victoria	Heidelberg west	Victoria
Australia	Australia, Victoria	Parkville	Victoria
Australia	Australia, New South Wales	Randwick	New South Wales
Canada	Canada	Montreal	Ontario
Canada	Canada	Toronto	Quebec
Canada	Canada, Toronto	Toronto	Ontario
Germany	Germany	Bielefeld	Westfalen-Lippe
Germany	Germany	Bonn	Nordrhein-Westfalen
Germany	Germany	Marberg	Hessen
Germany	Germany	Munchen	Bayern
Hungary	Hungary	Budapest
Israel	Israel	Haifa
Israel	Israel	Petah Tikvah
Israel	Israel	Ramat Gan
New Zealand	New Zealand	Christchurch	Canterbury
Poland	Poland	Gdansk
Poland	Poland	Katowice
Poland	Poland	Lublin
Spain	Spain	Gerona	Cataluyna
Spain	Spain	Madrid
Spain	Spain	Sevilla	Andalucia
Ukraine	Ukraine	Ivano-Frankivsk
Ukraine	Ukraine	Kharkiv
Ukraine	Ukraine	Odessa
Ukraine	Ukraine	Poltava
Ukraine	Ukraine	Ternopil
Ukraine	Ukraine	Vinnytsa
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, Illinois	Chicago	Illinois
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, California	Fresno	California
United States	United States, Texas	Greenville	Texas
United States	United States, New Jersey	Hackensack	New Jersey
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, 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, 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, California	Sacramento	California
United States	United States, Missouri	Saint Louis	Missouri
United States	United States, Minnesota	Saint Paul	Minnesota
United States	United States, Arizona	Scottsdale	Arizona
United States	United States, New York	Stony Brook	New York
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,  New Zealand,  Poland,  Spain,  Ukraine, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Safety Observation	Duration of participant study participation for collection of long term safety data	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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.	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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)	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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.	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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.	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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.	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Primary	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)	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Secondary	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)	6 hours after first dose of USL261 for each treated seizure cluster