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

NCT01390220 | Terminated Phase 3 Results DMC

• 2 other identifiers: P261-4012011-001318-32
• Study Type: interventional
• Target: 292
• Locations: 11 countries
• Sites: 90

Brief Summary

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

Conditions

Epilepsy

Keywords

Epilepsy; seizure clusters; acute repetitive seizures; rescue treatment; ARTEMIS

Outcome Measures

Primary Outcomes (1)

• Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)

  Treatment Success is defined as achieving both of the following: 1) termination of seizure(s) within 10 minutes after double-blind study drug administration, and 2) no recurrence of seizure(s) beginning 10 minutes after study drug administration to 6 hours after study drug administration. Participants who received the open-label second dose within 6 hours of administration of the double-blind dose were analyzed as having had a seizure.

  6 hours

Secondary Outcomes (3)

• Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose

  4 hours

• Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose

  24 hours

• Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose

  24 hours

Study Arms (2)

USL261

EXPERIMENTAL

intranasal midazolam 5mg

Drug: USL261

Placebo

EXPERIMENTAL

Intranasal placebo

Drug: Placebo

Interventions

USL261 DRUG

Also known as: Midazolam nasal spray (MDZ NS)

USL261

Placebo DRUG

Placebo

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma S.P.R.L.: lead

Study Sites (90)

United States, Arizona

Phoenix, 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

Irvine, California, United States

Location

United States, California

Loma Linda, 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

Gainesville, Florida, United States

Location

United States, Florida

Gulf Breeze, Florida, United States

Location

United States, Florida

Port Charlotte, Florida, United States

Location

United States, Florida

Tampa, 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, Kansas

Manhattan, Kansas, 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

Chesterfield, Missouri, United States

Location

United States, Missouri

St Louis, Missouri, United States

Location

United States, Nevada

Reno, Nevada, United States

Location

United States, New Hampshire

Lebanon, New Hampshire, United States

Location

United States, New Jersey

Flemington, New Jersey, 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, Ohio

Columbus, Ohio, United States

Location

United States, Oklahoma

Oklahoma City, Oklahoma, United States

Location

United States, Oregon

Portland, Oregon, 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

Fort Worth, Texas, United States

Location

United States, Texas

Greenville, Texas, United States

Location

United States, Texas

San Antonio, Texas, United States

Location

United States, Texas

Temple, Texas, United States

Location

United States, Virginia

Norfolk, Virginia, United States

Location

United States, Wisconsin

Madison, Wisconsin, United States

Location

Australia, New South Wales

Chatswood, New South Wales, Australia

Location

Australia, New South Wales

Randwick, New South Wales, Australia

Location

Australia, Queensland

Herston, Queensland, Australia

Location

Australia, Vctoria

Heidelberg West, Victoria, Australia

Location

Australia, Victoria

Parkville, Victoria, Australia

Location

Canada, Ontario

Toronto, Ontario, Canada

Location

Canada, Quebec

Montreal, Quebec, Canada

Location

Germany, Baden-Wurttemberg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Location

Germany, Bayern

Munich, Bavaria, Germany

Location

Germany, Hessen

Marburg, Hesse, Germany

Location

Germany, Nordrhein-Westfalen

Bonn, North Rhine-Westphalia, Germany

Location

Germany, Westfalen-Lippe

Bielefeld, Wetsfalen-Lippe, Germany

Location

Hungary

Budapest, Hungary

Location

Hungary

Kazincbarcika, Hungary

Location

Israel

Haifa, Israel

Location

Israel

Holon, Israel

Location

Israel

Jerusalem, Israel

Location

Israel

Petah Tikva, Israel

Location

Israel

Ramat Gan, Israel

Location

Israel

Tel Aviv, Israel

Location

Italy

Florence, Italy

Location

Italy

Genova, Italy

Location

Italy

Milan, Italy

Location

Italy

Napoli, Italy

Location

Italy

Pavia, Italy

Location

Italy

San Fermo della Battaglia, Italy

Location

New Zealand, Auklund

Grafton, Auklund, New Zealand

Location

New Zealand, Canterbury

Christchurch, Canterbury, New Zealand

Location

Poland

Gdansk, Poland

Location

Poland

Katowice, Poland

Location

Poland

Krakow, Poland

Location

Poland

Olsztyn, Poland

Location

Spain, Andalucia

Seville, Andalusia, Spain

Location

Spain, Catalonia

Barcelona, Catalonia, Spain

Location

Spain, Catalonia

Girona, Catalonia, Spain

Location

Spain, Madrid

Fuencarral-El Pardo, Madrid, Spain

Location

Spain, Madrid

Moncloa-Aravaca, Madrid, Spain

Location

Spain, Madrid

Pozuelo de Alarcón, Madrid, Spain

Location

Ukraine, Ivano-Frankivsk

Ivano-Frankivsk, Ukraine

Location

Ukraine

Kharkiv, Ukraine

Location

Ukraine

Odesa, Ukraine

Location

Ukraine

Poltava, Ukraine

Location

Ukraine

Ternopil, Ukraine

Location

Ukraine

Vinnytsia, 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 DERIVED

• 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.

  PMID: 31140596 DERIVED

MeSH Terms

Conditions

Epilepsy; Severe combined immunodeficiency with sensitivity to ionizing radiation

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2011
• First Posted: July 8, 2011
• Study Start: June 1, 2011
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: October 10, 2019
• Results First Posted: May 31, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); US (46); IT (6); ES (6); CA (2); DE (5); PL (4); IL (6); HU (2); UA (6); NZ (2)