Open-label Study of Midazolam Hydrochloride Oromucosal Solution (MHOS/SHP615) in Children With Status Epilepticus (Convulsive) in a Healthcare Setting in Japan
Condition: Nervous System Diseases
MeSH terms: Nervous System Diseases; Status Epilepticus
Intervention: SHP615
Intervention description: SHP615 oromucosal solution will be administered as a single age-specific dose (2.5, 5, 7.5 and 10 mg).
Intervention MeSH terms: Midazolam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 3 Months
Maximum age: 216 Months
Healthy volunteers: No
Keywords: Seizure; Midazolam hydrochloride; Convulsive

Summary:

      The purpose of this study is to assess the efficacy, safety and pharmacokinetics of
      MHOS/SHP615 administered buccally in children with status epilepticus (convulsive) in a
      healthcare setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female participants whose corrected gestational age is greater than or equal
             to (>=) 52 weeks (gestational weeks plus the number of weeks after birth) and less
             than (<) 18 years (and weight greater than [>] 5 kilogram [kg]), at the time of
             investigational product administration. If the participant's exact age is not known,
             the participant should be excluded.

          -  Parent, guardian, or legally authorized representative (LAR) of the child provides
             informed consent (and assent, when applicable per Shire policy and country
             regulations) to participate in the study prior to participation in any protocol
             specific procedures. The participant may be prescreened by the investigator in their
             clinical practice and the parent, guardian, or LAR may sign informed consent before
             the participant presents to the healthcare setting for treatment of the seizure.

          -  Participant with generalized tonic-clonic SE with seizures accompanied by loss of
             consciousness with any of the following characteristics persistent at the time of
             study drug administration:

               1. Currently presenting with seizure (convulsive) activity and 3 or more convulsions
                  within the preceding hour

               2. Currently presenting with seizure (convulsive) and 2 or more convulsions in
                  succession without recovery of consciousness

               3. Currently presenting with a single seizure (convulsive) lasting >=5 mins

        Exclusion Criteria:

          -  Female participants who are pregnant, suspected to be pregnant, or nursing.

          -  Subjects with major trauma, not necessarily restricted to the head, as the cause of
             the seizure.

          -  Subjects with seizures due to illegal drug or acute alcoholic intoxication.

          -  Subjects with known or suspected recurrent seizures due to illegal drug or alcohol
             withdrawal.

          -  Subjects with history of seizures of psychogenic origin.

          -  Subjects with seizures due to severe encephalitis or meningitis, as determined by the
             PI

          -  Subjects with known history of hypersensitivities, non-responsiveness or
             contraindications to benzodiazepines (ie, clinically significant respiratory
             depression, severe acute hepatic failure, myasthenia gravis, syndrome of sleep apnea,
             glaucoma with closed angle, use of concomitant drugs determined by the investigator to
             have a contraindication to the use of benzodiazepines.)

          -  Subjects with a known history of benzodiazepine abuse.

          -  Subjects who, in the judgment of the healthcare provider, have not responded to
             previous administrations of midazolam systemic therapies, including Midafresa and/or
             Dormicum.

          -  Subjects who need emergent surgical intervention and general anesthesia/intubation.

          -  Subjects with significant hypotension and cardiac dysrhythmia (example [eg],
             atrioventricular [AV] block of second or third degree, VT [ventricular tachycardia]).

          -  Subjects who have been receiving human immunodeficiency virus (HIV) protease
             inhibitors or HIV reverse transcriptase inhibitors.

          -  Subjects with current hypoglycemia (glucose <60 milligram per deciliter [mg/dL]) upon
             presentation at the hospital or healthcare setting.

          -  Subjects with severe cerebral anoxia (except cerebral palsy), in the judgment of the
             healthcare provider.

          -  Subjects have used an investigational product or been enrolled in a clinical study
             (including vaccine studies) that, in the investigator's opinion, may impact this
             Shire-sponsored study.

          -  Subjects has received antiseizure medication prior to arrival in the healthcare
             setting.

          -  Subjects has prior placement of a vagus nerve stimulator.