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

NCT03336645 | Completed Phase 3 Results

• 1 other identifier: SHP615-301
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 23

Brief 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.

Conditions

Nervous System Diseases

Keywords

Seizure; Midazolam hydrochloride; Convulsive

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Response Rate

  Response rate was defined as the percentage of participants with therapeutic success. Therapeutic success was defined as the cessation of visible seizure activity within 10 minutes with a sustained absence of visible seizure activity for 30 minutes following a single dose of MHOS/SHP615 without the need for additional rescue medication.

  From start of study drug administration up to 30 minutes post-dose

Secondary Outcomes (18)

• Percentage of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4 and 6 Hours

  From start of study drug administration up to 1, 4 and 6 hours post-dose

• Number of Participants With Time to Resolution of Seizures (Convulsions)

  From start of study drug administration up to follow-up (Day 8)

• Number of Participants With Time to Recovery of Consciousness

  From start of study drug administration up to follow-up (Day 8)

• Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE)

  10 minutes post-dose

• Percentage of Participants Who Failed to Respond to the Treatment With SHP615

  10 minutes post-dose

Study Arms (1)

SHP615

EXPERIMENTAL

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.

Drug: SHP615

Interventions

SHP615 DRUG

SHP615 oromucosal solution will be administered as a single age-specific dose (2.5, 5, 7.5 and 10 mg).

Also known as: Midazolam hydrochloride oromucosal solution, MHOS

SHP615

Eligibility Criteria

• Age: 3 Months - 216 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• Currently presenting with seizure (convulsive) activity and 3 or more convulsions within the preceding hour
• Currently presenting with seizure (convulsive) and 2 or more convulsions in succession without recovery of consciousness
• Currently presenting with a single seizure (convulsive) lasting \>=5 mins

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (23)

Yamanashi Prefectural Central Hospital

Kofu, Fujimi, 400-8506, Japan

Location

Gifu Prefectural General Medical Center

Gifu, Gifu, 500-8717, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, Kawadacho, 162-8666, Japan

Location

NHO Minami-Okayama Medical Center

Okayama, Okayama-ken, 701-0304, Japan

Location

Tokyo Women's Medical University Yachiyo Medical Center

Yachiyo, Owada Shinden, 276-8524, Japan

Location

Jichi Children's Medical Center Tochigi

Saitama-shi, Saitama, 330-8503, Japan

Location

Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Shizuoka, 420-8688, Japan

Location

Fukuoka Children's Hospital(NW)

Fukuoka, 813-0017, Japan

Location

NHO Hokkaido Medical Center

Hokkaidō, 063-0005, Japan

Location

Kumamoto Saishunso National Hospital

Kumamoto, 861-1196, Japan

Location

NHO Nagasaki Medical Center

Nagasaki, 856-8562, Japan

Location

NHO Nishi Niigata Chuo National Hospital

Niigata, 950-2085, Japan

Location

Okayama University Hospital

Okayama, 700-0914, Japan

Location

Nakano Children's Hospital

Osaka, 535-0022, Japan

Location

Osaka Women's and Children's Hospital(NW)

Osaka, 594-1101, Japan

Location

Aichi Children's Health and Medical Center(NW)

Ōbu, 474-8710, Japan

Location

Saitama Children's Medical Center(NW)

Saitama, 330-8777, Japan

Location

Osaka University Hospital

Suita, 565-0871, Japan

Location

National Center Hospital, NCNP

Tokyo, 187-0031, Japan

Location

Tottori University Hospital

Tottori, 683-8504, Japan

Location

Osaka University Hospital

Yamadaoka, 565-0871, Japan

Location

Kanagawa Children's Medical Center(NW)

Yokohama, 232-0066, Japan

Location

MeSH Terms

Conditions

Nervous System Diseases; Seizures

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Physician
• Organization: Shire

ClinicalTransparency@takeda.com

1 866-842-5335

Study Officials

• Shire Study Physician

  Shire

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 8, 2017
• Study Start: October 23, 2017
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: July 31, 2020
• Results First Posted: July 31, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (23)