Study of Midazolam Hydrochloride Oromucosal Solution (MHOS/SHP615) in Pediatric Patients With Status Epilepticus (Convulsive) in the Community Setting

NCT03336450 | Completed Phase 3 Results

• 1 other identifier: SHP615-302
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 23

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.

Conditions

Nervous System Diseases

Outcome Measures

Primary Outcomes (2)

• Efficacy: Number of Participants With Therapeutic Success

  Therapeutic success was defined as cessation of visible seizure activity within 10 minutes and sustained absence of visible seizure activity for 30 minutes following a single dose of SHP615 without the need for additional rescue medication. Number of participants with therapeutic success were reported.

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

• Safety: Number of Participants With Respiratory Depression

  Respiratory depression, included the following measures within 24 hours after administration of the IP: i) Persistent decrease in oxygen saturation to \<92 percent (%) measured up to 24 hours post-dose (i.e., \<92% on room air for 2 minutes or more after dosing while monitoring \[per healthcare setting protocol and/or the clinical judgment of the physician\]. ii) Increase in respiratory effort such that assisted ventilation is used (bag-valve-mask ventilation or endotracheal intubation). Number of participants with respiratory depression were reported.

  Up to 24 hours post-dose

Secondary Outcomes (13)

• Efficacy: Number 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

• Efficacy: Time to Resolution of Seizures (Convulsions)

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

• Efficacy: Time to Recovery of Consciousness

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

• Efficacy: Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE) 10 Minutes After Administration of SHP615

  10 minutes post-dose

• Efficacy: Percentage of Participants Who Failed to Respond to 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; Drug: MHOS/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: MHOS, Midazolam hydrochloride oromucosal solution

SHP615

MHOS/SHP615 DRUG

MHOS/SHP615

SHP615

Eligibility Criteria

• Age: 6 Months - 216 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• Properly administer MHOS/SHP615.
• 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.)
• 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:
• 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) persisting greater than or equal to (\>=) 5 minutes.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (23)

Yamanashi Prefectural Central Hospital

Kofu, Fujimi, 400-8506, Japan

Location

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, 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

Shizuoka Institute of Epilepsy and Neurological Disorders

Shizuoka, Shizuoka, 420-8688, Japan

Location

Fukuoka Children's Hospital(NW)

Fukuoka, 813-0017, Japan

Location

Gifu Prefectural General Medical Center

Gifu, 500-8717, 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

Jichi Children's Medical Center Tochigi

Saitama-shi, 330-8503, Japan

Location

Osaka University Hospital

Suita, 565-0871, Japan

Location

Tokyo Women's Medical University Hospital

Tokyo, 162-8666, 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

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda Development Center Americas

  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: April 23, 2018
• Primary Completion: October 13, 2020
• Study Completion: October 13, 2020
• Last Updated: September 14, 2021
• Results First Posted: September 14, 2021

Record last verified: 2021-08

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)