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

NCT01529034 | Terminated Phase 3 Results

• 2 other identifiers: P261-4022011-004109-25
• Study Type: interventional
• Target: 175
• Locations: 10 countries
• Sites: 58

Brief Summary

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

Conditions

Epilepsy

Keywords

Epilepsy; seizure clusters; acute repetitive seizures; rescue treatment

Outcome Measures

Primary Outcomes (9)

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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 Outcomes (1)

• Number of Treated Seizure Clusters Meeting Criteria for Treatment Success

  6 hours after first dose of USL261 for each treated seizure cluster

Study Arms (1)

USL261

EXPERIMENTAL

Intranasal midazolam 5 mg

Drug: USL261

Interventions

USL261 DRUG

USL261

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (58)

United States, Arizona

Phoenix, Arizona, United States

Location

United States, Arizona

Scottsdale, Arizona, United States

Location

United States, Arizona

Tucson, Arizona, United States

Location

United States, Arkansas

Little Rock, Arkansas, United States

Location

United States, California

Fresno, California, United States

Location

United States, California

Sacramento, California, United States

Location

United States, California

Ventura, California, United States

Location

United States, Colorado

Aurora, Colorado, United States

Location

United States, Connecticut

New Haven, Connecticut, United States

Location

United States, Florida

Port Charlotte, Florida, United States

Location

United States, Florida

Wellington, Florida, United States

Location

United States, Idaho

Boise, Idaho, United States

Location

United States, Illinois

Chicago, Illinois, United States

Location

United States, Kentucky

Lexington, Kentucky, United States

Location

United States, Maryland

Baltimore, Maryland, United States

Location

United States, Michigan

Detroit, Michigan, United States

Location

United States, Minnesota

Saint Paul, Minnesota, United States

Location

United States, Missouri

St Louis, Missouri, United States

Location

United States, New Hampshire

Lebanon, New Hampshire, United States

Location

United States, New Jersey

Hackensack, New Jersey, United States

Location

United States, New York

New York, New York, United States

Location

United States, New York

Stony Brook, New York, United States

Location

United States, New York

The Bronx, New York, United States

Location

United States, North Carolina

Durham, North Carolina, United States

Location

United States, North Carolina

Winston-Salem, North Carolina, United States

Location

United States, Oklahoma

Oklahoma City, Oklahoma, United States

Location

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

Location

United States, Tennessee

Memphis, Tennessee, United States

Location

United States, Tennessee

Nashville, Tennessee, United States

Location

United States, Texas

Dallas, Texas, United States

Location

United States, Texas

Greenville, Texas, United States

Location

Australia, New South Wales

Randwick, New South Wales, Australia

Location

Australia, Victoria

Heidelberg West, Victoria, Australia

Location

Australia, Victoria

Parkville, Victoria, Australia

Location

Canada

Montreal, Ontario, Canada

Location

Canada, Toronto

Toronto, Ontario, Canada

Location

Canada

Toronto, Quebec, Canada

Location

Germany

München, Bavaria, Germany

Location

Germany

Marberg, Hesse, Germany

Location

Germany

Bonn, North Rhine-Westphalia, Germany

Location

Germany

Bielefeld, Westfalen-Lippe, Germany

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Hungary

Budapest, Hungary

Location

Israel

Haifa, Israel

Location

Israel

Petah Tikvah, Israel

Location

Israel

Ramat Gan, Israel

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New Zealand

Christchurch, Canterbury, New Zealand

Location

Poland

Gdansk, Poland

Location

Poland

Katowice, Poland

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Poland

Lublin, Poland

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Spain

Seville, Andalusia, Spain

Location

Spain

Girona, Cataluyna, Spain

Location

Spain

Madrid, Spain

Location

Ukraine

Ivano-Frankivsk, Ukraine

Location

Ukraine

Kharkiv, Ukraine

Location

Ukraine

Odesa, Ukraine

Location

Ukraine

Poltava, Ukraine

Location

Ukraine

Ternopil, Ukraine

Location

Ukraine

Vinnytsa, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 36410152 RESULT

• 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.

  PMID: 31353457 DERIVED

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

Open-label, non-comparative design. Potential participation bias due to participants and/or caregiver perceived efficacy/safety in prior study. Seizure data capture in diaries diminished over time in some participants due to length of study.

Results Point of Contact

• Title: David Sequeira
• Organization: Proximagen, LLC

dsequeira@proximagen.com

952-658-7438

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2012
• First Posted: February 8, 2012
• Study Start: July 1, 2012
• Primary Completion: April 1, 2017
• Last Updated: January 20, 2023
• Results First Posted: June 25, 2019

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1); AU (3); US (31); DE (4); ES (3); IL (3); PL (3); CA (3); UA (6); NZ (1)