Clinical trial NCT03336450: Study of Midazolam Hydrochloride Oromucosal Solution (MHOS/SHP615) in Pediatric Patients With Status Epilepticus (Convulsive) in the Community Setting
Official title: A Phase 3, Multicenter, Open-label Extension Study of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in Community Settings
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nervous System Diseases
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2017-11-08
Enrollment: 3
Sex: ALL
Minimum age (years): 6
Maximum age (years): 216
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the investigational treatment, MHOS/SHP615, is safe and effective in children with status epilepticus (SE) (convulsive) in the community setting. This study is open-label extension for patients who completed the SHP615-301 study and who tolerated and responded to MHOS/SHP615 treatment in the hospital setting.


Eligibility criteria: Inclusion Criteria:

* Subjects who completed the SHP615-301 study and who tolerated and responded to treatment with MHOS/SHP615 in the hospital and/or emergency room, and are considered stable for discharge from the hospital.
* Subjects who are greater than (\>) 6 months and less than (\<) 18 years of age at the time of investigational product administration. If the subject's exact age is not known, the subject should be excluded.
* Parent, guardian, or legally authorized representative of the child who provides informed consent and assent (when applicable) to participate in the study after initial stabilization of the subject with SE in hospital or emergency room during the SHP615-301 study. The subject also provides informed consent prior to participation, where applicable.
* Parent, guardian, or legally authorized representative who have received appropriate training/education and are deemed qualified by the investigator and are willing to:

  1. Properly administer MHOS/SHP615.
  2. Record seizure information and dosing of MHOS/SHP615 in a subject diary (including time of seizure onset, type of seizure, time necessary to administer MHOS/SHP615, time between MHOS/SHP615 administration to seizure cessation, etc.)
  3. Follow the necessary instructions to secure the safety of the subject.
* Subjects who experience 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) persisting greater than or equal to (\>=) 5 minutes.

Exclusion Criteria:

* Female subjects 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 known or suspected recurrent seizures due to illegal drug or alcohol withdrawal.
* Subjects with seizures due to illegal drug or acute alcoholic intoxication.
* Subjects with seizures of psychogenic origin.
* Subjects with seizures due to severe encephalitis or meningitis, as determined by the PI
* Subjects with known history of hypersensitivities, nonresponsiveness or contraindications to benzodiazepines (that is (ie), clinically significant respiratory depression, severe acute hepatic failure, myasthenia gravis, syndrome of sleep apnea, glaucoma with closed angle, or 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 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 who have been receiving human immunodeficiency virus (HIV) protease inhibitors or HIV reverse transcriptase inhibitors.
* Subjects with severe cerebral anoxia (except cerebral palsy), in the judgment of the healthcare provider.
* 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.
* Subject has prior placement of a vagus nerve stimulator.

Primary outcomes:
measure: Efficacy: Number of Participants With Therapeutic Success
timeFrame: From start of study drug administration up to 30 minutes post-dose
measure: Safety: Number of Participants With Respiratory Depression
timeFrame: Up to 24 hours post-dose
Secondary outcomes:
measure: Efficacy: Number of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4, and 6 Hours
timeFrame: From start of study drug administration up to 1, 4, and 6 hours post-dose
measure: Efficacy: Time to Resolution of Seizures (Convulsions)
timeFrame: From start of study drug administration up to follow-up (Day 8)
measure: Efficacy: Time to Recovery of Consciousness
timeFrame: From start of study drug administration up to follow-up (Day 8)
measure: Efficacy: Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE) 10 Minutes After Administration of SHP615
timeFrame: 10 minutes post-dose
measure: Efficacy: Percentage of Participants Who Failed to Respond to Treatment With SHP615
timeFrame: 10 minutes post-dose
measure: Safety: Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to follow-up (Day 8)
measure: Safety: Number of Participants Analyzed for Sedation or Agitation Measured by the Riker Sedation-Agitation Scale
timeFrame: 1, 4, 6, and 24 hours post-dose
measure: Safety: Number of Participants With Buccal Irritation Reported as Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 6 hours post-dose
measure: Safety: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to follow-up (Day 8)
measure: Safety: Number of Participants With Clinically Significant Change in Vital Signs Reported as TEAEs
timeFrame: From start of study drug administration up to 24 hours post-dose
measure: Safety: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as TEAEs
timeFrame: From start of study drug administration up to 24 hours post-dose
measure: Safety: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as TEAEs
timeFrame: From start of study drug administration up to 24 hours post-dose
measure: Safety: Percentage of Participants With Normal Oxygen Saturation Values Collected During Hospital Setting
timeFrame: 0.5, 1, 4, 6 and 24 hours post-dose
Other outcomes:
Locations:
city: Kofu
country: Japan
facility: Yamanashi Prefectural Central Hospital
state: Fujimi
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Okayama
country: Japan
facility: NHO Minami-Okayama Medical Center
state: Okayama Prefecture
city: Yachiyo
country: Japan
facility: Tokyo Women's Medical University Yachiyo Medical Center
state: Owada Shinden
city: Shizuoka
country: Japan
facility: Shizuoka Institute of Epilepsy and Neurological Disorders
state: Shizuoka Prefecture
city: Fukuoka
country: Japan
facility: Fukuoka Children's Hospital(NW)
city: Gifu
country: Japan
facility: Gifu Prefectural General Medical Center
city: Hokkaidō
country: Japan
facility: NHO Hokkaido Medical Center
city: Kumamoto
country: Japan
facility: Kumamoto Saishunso National Hospital
city: Nagasaki
country: Japan
facility: NHO Nagasaki Medical Center
city: Niigata
country: Japan
facility: NHO Nishi Niigata Chuo National Hospital
city: Obu
country: Japan
facility: Aichi Children's Health and Medical Center(NW)
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Nakano Children's Hospital
city: Osaka
country: Japan
facility: Osaka Women's and Children's Hospital(NW)
city: Saitama-shi
country: Japan
facility: Jichi Children's Medical Center Tochigi
city: Saitama
country: Japan
facility: Saitama Children's Medical Center(NW)
city: Suita
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Tokyo
country: Japan
facility: National Center Hospital, NCNP
city: Tottori
country: Japan
facility: Tottori University Hospital
city: Yamadaoka
country: Japan
facility: Osaka University Hospital
city: Yokohama
country: Japan
facility: Kanagawa Children's Medical Center(NW)
Study officials:
affiliation: Takeda Development Center Americas
name: Study Director
role: STUDY_DIRECTOR
References: