Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters (ARTEMIS1)

October 8, 2019 updated by: UCB Biopharma S.P.R.L.

A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Intranasal Midazolam (USL261) in the Outpatient Treatment of Subjects With Seizure Clusters. ARTEMIS-1: Acute Rescue Therapy in Epilepsy With Midazolam Intranasal Spray-1

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
292

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Chatswood, New South Wales, Australia
        • Australia, New South Wales
      • Randwick, New South Wales, Australia
        • Australia, New South Wales
    • Queensland
      • Herston, Queensland, Australia
        • Australia, Queensland
    • Victoria
      • Heidelberg West, Victoria, Australia
        • Australia, Vctoria
      • Parkville, Victoria, Australia
        • Australia, Victoria
  • Canada
    • Ontario
      • Toronto, Ontario, Canada
        • Canada, Ontario
    • Quebec
      • Montreal, Quebec, Canada
        • Canada, Quebec
  • Germany
    • Baden-Wurttemberg
      • Freiburg, Baden-Wurttemberg, Germany
        • Germany, Baden-Wurttemberg
    • Bayern
      • Munich, Bayern, Germany
        • Germany, Bayern
    • Hessen
      • Marburg, Hessen, Germany
        • Germany, Hessen
    • Nordrhein-Westfalen
      • Bonn, Nordrhein-Westfalen, Germany
        • Germany, Nordrhein-Westfalen
    • Wetsfalen-Lippe
      • Bielefeld, Wetsfalen-Lippe, Germany
        • Germany, Westfalen-Lippe
  • Hungary
      • Budapest, Hungary
        • Hungary
      • Kazincbarcika, Hungary
        • Hungary
  • Israel
      • Haifa, Israel
        • Israel
      • Holon, Israel
        • Israel
      • Jerusalem, Israel
        • Israel
      • Petach Tikva, Israel
        • Israel
      • Ramat Gan, Israel
        • Israel
      • Tel Aviv, Israel
        • Israel
  • Italy
      • Firenze, Italy
        • Italy
      • Genova, Italy
        • Italy
      • Milano, Italy
        • Italy
      • Napoli, Italy
        • Italy
      • Pavia, Italy
        • Italy
      • San Fermo della Battaglia, Italy
        • Italy
  • New Zealand
    • Auklund
      • Grafton, Auklund, New Zealand
        • New Zealand, Auklund
    • Canterbury
      • Christchurch, Canterbury, New Zealand
        • New Zealand, Canterbury
  • Poland
      • Gdansk, Poland
        • Poland
      • Katowice, Poland
        • Poland
      • Krakow, Poland
        • Poland
      • Olsztyn, Poland
        • Poland
  • Spain
    • Andalucia
      • Sevilla, Andalucia, Spain
        • Spain, Andalucia
    • Catalonia
      • Barcelona, Catalonia, Spain
        • Spain, Catalonia
      • Girona, Catalonia, Spain
        • Spain, Catalonia
    • Madrid
      • Fuencarral-El Pardo, Madrid, Spain
        • Spain, Madrid
      • Moncloa-Aravaca, Madrid, Spain
        • Spain, Madrid
      • Pozuelo De Alarcón, Madrid, Spain
        • Spain, Madrid
  • Ukraine
      • Ivano-Frankivsk, Ukraine
        • Ukraine, Ivano-Frankivsk
      • Kharkiv, Ukraine
        • Ukraine
      • Odessa, Ukraine
        • Ukraine
      • Poltava, Ukraine
        • Ukraine
      • Ternopil, Ukraine
        • Ukraine
      • Vinnytsya, Ukraine
        • Ukraine
  • United States
    • Arizona
      • Phoenix, Arizona, United States
        • United States, Arizona
      • Tucson, Arizona, United States
        • United States, Arizona
    • Arkansas
      • Little Rock, Arkansas, United States
        • United States, Arkansas
    • 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, California
    • Colorado
      • Aurora, Colorado, United States
        • United States, Colorado
    • Connecticut
      • New Haven, Connecticut, United States
        • United States, Connecticut
    • 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, Florida
    • Idaho
      • Boise, Idaho, United States
        • United States, Idaho
    • Illinois
      • Chicago, Illinois, United States
        • United States, Illinois
    • Kansas
      • Manhattan, Kansas, United States
        • United States, Kansas
    • Kentucky
      • Lexington, Kentucky, United States
        • United States, Kentucky
    • Maryland
      • Baltimore, Maryland, United States
        • United States, Maryland
    • Michigan
      • Detroit, Michigan, United States
        • United States, Michigan
    • Minnesota
      • Saint Paul, Minnesota, United States
        • United States, Minnesota
    • Missouri
      • Chesterfield, Missouri, United States
        • United States, Missouri
      • Saint Louis, Missouri, United States
        • United States, Missouri
    • Nevada
      • Reno, Nevada, United States
        • United States, Nevada
    • New Hampshire
      • Lebanon, New Hampshire, United States
        • United States, New Hampshire
    • New Jersey
      • Flemington, New Jersey, United States
        • United States, New Jersey
      • Hackensack, New Jersey, United States
        • United States, New Jersey
    • New York
      • Bronx, New York, 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
    • North Carolina
      • Durham, North Carolina, United States
        • United States, North Carolina
      • Winston-Salem, North Carolina, United States
        • United States, North Carolina
    • Ohio
      • Columbus, Ohio, United States
        • United States, Ohio
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • United States, Oklahoma
    • Oregon
      • Portland, Oregon, United States
        • United States, Oregon
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • United States, Pennsylvania
    • Tennessee
      • Memphis, Tennessee, United States
        • United States, Tennessee
      • Nashville, Tennessee, United States
        • United States, Tennessee
    • 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, Texas
    • Virginia
      • Norfolk, Virginia, United States
        • United States, Virginia
    • Wisconsin
      • Madison, Wisconsin, United States
        • United States, Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: USL261
intranasal midazolam 5mg
Drug: USL261
Other Names:
  • Midazolam nasal spray (MDZ NS)
Experimental: Placebo
Intranasal placebo
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
Time Frame: 6 hours
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
Time Frame: 4 hours
Participants with recurrence of seizure(s) >10 minutes and up to 4 hours after administration of the double-blind dose in the CP. Participants who received the open-label second dose within 4 hours of administration of the double-blind dose were analyzed as having had a seizure.
4 hours
Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Time Frame: 24 hours
Occurrence of next seizure with a start time >10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration.
24 hours
Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Time Frame: 24 hours
Time to next seizure with a start time >10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration.
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UCB Biopharma S.P.R.L.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 6, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 8, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 10, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 8, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P261-401
  • 2011-001318-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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