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

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ClinicalTrials.gov Identifier: NCT01529034
Recruitment Status : Terminated
First Posted : February 8, 2012
Results First Posted : June 25, 2019
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma S.P.R.L. )

Tracking Information
First Submitted Date  ICMJE February 3, 2012
First Posted Date  ICMJE February 8, 2012
Results First Submitted Date  ICMJE May 9, 2019
Results First Posted Date  ICMJE June 25, 2019
Last Update Posted Date October 18, 2019
Actual Study Start Date  ICMJE July 2012
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2019)
  • Duration of Safety Observation [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    Duration of participant study participation for collection of long term safety data
  • Participants Meeting Predefined Safety Criteria for Vital Signs [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    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 [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    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 [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    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 [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    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 [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
  • Participant Change in B-SIT Score [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    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 [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    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 [ Time Frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study. ]
    Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2012)
Long-term safety and tolerability
Adverse events, clinical laboratory assessments, sedation, vital signs, physical exams, C-SSRS
Change History Complete list of historical versions of study NCT01529034 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success [ Time Frame: 6 hours after first dose of USL261 for each treated seizure cluster ]
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)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2012)
Treatment Success
Termination of seizure(s) within 10 minutes and no recurrence within 4 hours after study drug administration
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Long-term Safety and Tolerability of USL261 in Patients With Seizure Clusters
Official Title  ICMJE An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE Drug: USL261
Study Arms  ICMJE Experimental: USL261
Intranasal midazolam 5 mg
Intervention: Drug: USL261
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 19, 2017)
175
Original Estimated Enrollment  ICMJE
 (submitted: February 7, 2012)
155
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Germany,   Hungary,   Israel,   New Zealand,   Poland,   Spain,   Ukraine,   United States
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT01529034
Other Study ID Numbers  ICMJE P261-402
2011-004109-25 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party UCB Pharma ( UCB Biopharma S.P.R.L. )
Study Sponsor  ICMJE UCB Biopharma S.P.R.L.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account UCB Pharma
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP