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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01390220
Recruitment Status : Terminated
First Posted : July 8, 2011
Results First Posted : May 31, 2019
Last Update Posted : May 31, 2019
Information provided by (Responsible Party):
Proximagen, LLC

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

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 292 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 2011
Actual Primary Completion Date : March 2017
Actual Study Completion Date : March 2017

Arm Intervention/treatment
Experimental: USL261
intranasal midazolam 5mg
Drug: USL261
Other Name: Midazolam nasal spray (MDZ NS)

Experimental: Placebo
Intranasal placebo
Drug: Placebo

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. Occurrence of and 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.

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

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

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 identifier (NCT number): NCT01390220

  Show 90 Study Locations
Sponsors and Collaborators
Proximagen, LLC
  Study Documents (Full-Text)

Documents provided by Proximagen, LLC:
Study Protocol  [PDF] May 20, 2015
Statistical Analysis Plan  [PDF] April 14, 2017

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Proximagen, LLC Identifier: NCT01390220     History of Changes
Other Study ID Numbers: P261-401
2011-001318-32 ( EudraCT Number )
First Posted: July 8, 2011    Key Record Dates
Results First Posted: May 31, 2019
Last Update Posted: May 31, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Proximagen, LLC:
seizure clusters
acute repetitive seizures
rescue treatment

Additional relevant MeSH terms:
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Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action