Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters

NCT ID: NCT01390220

Last Updated: 2019-10-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 292 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2017-03-31

Brief Summary

The purpose of this study is to examine the safety and effectiveness of USL261 for the outpatient treatment of seizure clusters.

Detailed Description

Qualifying participants underwent an in-clinic administration (Test Dose Phase [TDP]) of two doses of USL261 (intranasal midazolam 5 mg), separated by 10 minutes, in the absence of seizures. Eligible participants were then randomized to USL261 versus Placebo in an outpatient Comparative Phase (CP). When the participant had a qualifying seizure cluster episode, as described in an individualized patient management plan, the participant's caregiver administered the double-blind dose. An open-label USL261 dose could be administered after 10 minutes and up to 6 hours after the double-blind dose, if the participant had persistent or recurrent seizures. Initial participants could not proceed to CP until an independent data safety monitoring board (DSMB) reviewed safety data from at least the first 25 participants in TDP; the DSMB performed additional safety reviews at pre-set intervals based on enrollment.

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

USL261

intranasal midazolam 5mg

Group Type: EXPERIMENTAL

USL261

Intervention Type: DRUG

Placebo

Intranasal placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Interventions

USL261

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Midazolam nasal spray (MDZ NS)

Eligibility Criteria

Inclusion Criteria

• Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes
• Has an established diagnosis of partial or generalized epilepsy that includes the following:

• A documented history of seizure clusters lasting a minimum of 10 minutes
• Seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure activity (if any)
• A second seizure in the seizure cluster typically occurring within 6 hours from the time of cluster recognition
• A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures
• A seizure cluster pattern established > 3 months before Visit 1
• A frequency of ≥ 3 seizure clusters during the year before Visit 1
• At least 1 seizure cluster occurring ≤ 4 months before Visit 1
• Seizure cluster pattern is confirmed by a central reviewer
• Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
• Weight is 40 kg to 125 kg, inclusive

Exclusion Criteria

• Has a neurological disorder that is likely to progress in the next year
• Has severe chronic cardio-respiratory disease
• Has had psychogenic, non-epileptic seizure(s) within the 5 years before Visit 1
• Has a history of their stereotypical seizure cluster progressing to status epilepticus within the 2 years before Visit 1
• Has a history of acute narrow-angle glaucoma.
• Has had active suicidal plan/intent or active suicidal thoughts in the 6 months before Visit 1 or a suicide attempt in the past 5 years
• Currently using a vagal nerve stimulator (VNS) unless the device has been implanted for at least 6 months and the setting stable for 4 weeks before Visit 1

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UCB Biopharma S.P.R.L.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

United States, Arizona

Phoenix, Arizona, United States

United States, Arizona

Tucson, Arizona, United States

United States, Arkansas

Little Rock, Arkansas, United States

United States, California

Fresno, California, United States

United States, California

Irvine, California, United States

United States, California

Loma Linda, California, United States

United States, California

Sacramento, California, United States

United States, California

Ventura, California, United States

United States, Colorado

Aurora, Colorado, United States

United States, Connecticut

New Haven, Connecticut, United States

United States, Florida

Gainesville, Florida, United States

United States, Florida

Gulf Breeze, Florida, United States

United States, Florida

Port Charlotte, Florida, United States

United States, Florida

Tampa, Florida, United States

United States, Florida

Wellington, Florida, United States

United States, Idaho

Boise, Idaho, United States

United States, Illinois

Chicago, Illinois, United States

United States, Kansas

Manhattan, Kansas, United States

United States, Kentucky

Lexington, Kentucky, United States

United States, Maryland

Baltimore, Maryland, United States

United States, Michigan

Detroit, Michigan, United States

United States, Minnesota

Saint Paul, Minnesota, United States

United States, Missouri

Chesterfield, Missouri, United States

United States, Missouri

St Louis, Missouri, United States

United States, Nevada

Reno, Nevada, United States

United States, New Hampshire

Lebanon, New Hampshire, United States

United States, New Jersey

Flemington, New Jersey, United States

United States, New Jersey

Hackensack, New Jersey, United States

United States, New York

New York, New York, United States

United States, New York

Stony Brook, New York, United States

United States, New York

The Bronx, New York, United States

United States, North Carolina

Durham, North Carolina, United States

United States, North Carolina

Winston-Salem, North Carolina, United States

United States, Ohio

Columbus, Ohio, United States

United States, Oklahoma

Oklahoma City, Oklahoma, United States

United States, Oregon

Portland, Oregon, United States

United States, Pennsylvania

Philadelphia, Pennsylvania, United States

United States, Tennessee

Memphis, Tennessee, United States

United States, Tennessee

Nashville, Tennessee, United States

United States, Texas

Dallas, Texas, United States

United States, Texas

Fort Worth, Texas, United States

United States, Texas

Greenville, Texas, United States

United States, Texas

San Antonio, Texas, United States

United States, Texas

Temple, Texas, United States

United States, Virginia

Norfolk, Virginia, United States

United States, Wisconsin

Madison, Wisconsin, United States

Australia, New South Wales

Chatswood, New South Wales, Australia

Australia, New South Wales

Randwick, New South Wales, Australia

Australia, Queensland

Herston, Queensland, Australia

Australia, Vctoria

Heidelberg West, Victoria, Australia

Australia, Victoria

Parkville, Victoria, Australia

Canada, Ontario

Toronto, Ontario, Canada

Canada, Quebec

Montreal, Quebec, Canada

Germany, Baden-Wurttemberg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Germany, Bayern

Munich, Bavaria, Germany

Germany, Hessen

Marburg, Hesse, Germany

Germany, Nordrhein-Westfalen

Bonn, North Rhine-Westphalia, Germany

Germany, Westfalen-Lippe

Bielefeld, Wetsfalen-Lippe, Germany

Hungary

Budapest, , Hungary

Hungary

Kazincbarcika, , Hungary

Israel

Haifa, , Israel

Israel

Holon, , Israel

Israel

Jerusalem, , Israel

Israel

Petah Tikva, , Israel

Israel

Ramat Gan, , Israel

Israel

Tel Aviv, , Israel

Italy

Florence, , Italy

Italy

Genova, , Italy

Italy

Milan, , Italy

Italy

Napoli, , Italy

Italy

Pavia, , Italy

Italy

San Fermo della Battaglia, , Italy

New Zealand, Auklund

Grafton, Auklund, New Zealand

New Zealand, Canterbury

Christchurch, Canterbury, New Zealand

Poland

Gdansk, , Poland

Poland

Katowice, , Poland

Poland

Krakow, , Poland

Poland

Olsztyn, , Poland

Spain, Andalucia

Seville, Andalusia, Spain

Spain, Catalonia

Barcelona, Catalonia, Spain

Spain, Catalonia

Girona, Catalonia, Spain

Spain, Madrid

Fuencarral-El Pardo, Madrid, Spain

Spain, Madrid

Moncloa-Aravaca, Madrid, Spain

Spain, Madrid

Pozuelo de Alarcón, Madrid, Spain

Ukraine, Ivano-Frankivsk

Ivano-Frankivsk, , Ukraine

Ukraine

Kharkiv, , Ukraine

Ukraine

Odesa, , Ukraine

Ukraine

Poltava, , Ukraine

Ukraine

Ternopil, , Ukraine

Ukraine

Vinnytsia, , Ukraine

Countries

United States; Australia; Canada; Germany; Hungary; Israel; Italy; New Zealand; Poland; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 36410152 (View on PubMed)

Detyniecki K, Van Ess PJ, Sequeira DJ, Wheless JW, Meng TC, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters-a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019 Sep;60(9):1797-1808. doi: 10.1111/epi.15159. Epub 2019 May 29.

Reference Type: DERIVED

PMID: 31140596 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2011-001318-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P261-401

Identifier Type: -

Identifier Source: org_study_id