Open-label Study of Midazolam Hydrochloride Oromucosal Solution (MHOS/SHP615) in Children With Status Epilepticus (Convulsive) in a Healthcare Setting in Japan

Shire

Status and phase: Completed; Phase 3

Conditions: Nervous System Diseases

Treatments: Drug: SHP615

Study type: Interventional

Funder types: Industry

Identifiers

NCT03336645

SHP615-301

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 3 to 216 months old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

SHP615

Experimental group

Description:

Participants will receive a single age-specific dose (approximately 0.25 to 0.5 milligram per kilogram \[mg/kg\] as midazolam) of SHP615 oromucosal solution through buccal route upon onset of seizures.

Treatment:

Drug: SHP615