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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 : September 12, 2019
Sponsor:
Information provided by (Responsible Party):
Proximagen, LLC

Brief Summary:
The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: USL261 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters
Actual Study Start Date : July 2012
Actual Primary Completion Date : April 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy Seizures

Arm Intervention/treatment
Experimental: USL261
Intranasal midazolam 5 mg
Drug: USL261



Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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)

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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)


Secondary Outcome Measures :
  1. 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)



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01529034


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Locations
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United States, Arizona
United States, Arizona
Phoenix, Arizona, United States
United States, Arizona
Scottsdale, Arizona, United States
United States, Arizona
Tucson, Arizona, United States
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Little Rock, Arkansas, United States
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Sacramento, California, United States
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Detroit, Michigan, United States
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Saint Louis, Missouri, United States
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Lebanon, New Hampshire, United States
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Hackensack, New Jersey, United States
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Bronx, New York, United States
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Stony Brook, New York, United States
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Durham, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Oklahoma City, Oklahoma, United States
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Philadelphia, Pennsylvania, United States
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Memphis, Tennessee, United States
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Nashville, Tennessee, United States
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Greenville, Texas, United States
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Heidelberg west, Victoria, Australia
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Parkville, Victoria, Australia
Canada, Ontario
Canada
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Canada
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Germany
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Munchen, Bayern, Germany
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Marberg, Hessen, Germany
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Bonn, Nordrhein-Westfalen, Germany
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Bielefeld, Westfalen-Lippe, Germany
Hungary
Hungary
Budapest, Hungary
Israel
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Haifa, Israel
Israel
Petah Tikvah, Israel
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Ramat Gan, Israel
New Zealand
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Christchurch, Canterbury, New Zealand
Poland
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Gdansk, Poland
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Katowice, Poland
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Lublin, Poland
Spain
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Sevilla, Andalucia, Spain
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Gerona, Cataluyna, Spain
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Madrid, Spain
Ukraine
Ukraine
Ivano-Frankivsk, Ukraine
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Kharkiv, Ukraine
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Odessa, Ukraine
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Poltava, Ukraine
Ukraine
Ternopil, Ukraine
Ukraine
Vinnytsa, Ukraine
Sponsors and Collaborators
Proximagen, LLC
  Study Documents (Full-Text)

Documents provided by Proximagen, LLC:
Study Protocol  [PDF] May 20, 2015
Statistical Analysis Plan  [PDF] May 15, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Proximagen, LLC
ClinicalTrials.gov Identifier: NCT01529034     History of Changes
Other Study ID Numbers: P261-402
2011-004109-25 ( EudraCT Number )
First Posted: February 8, 2012    Key Record Dates
Results First Posted: June 25, 2019
Last Update Posted: September 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Proximagen, LLC:
Epilepsy
seizure clusters
acute repetitive seizures
rescue treatment
Additional relevant MeSH terms:
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Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms