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

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ClinicalTrials.gov Identifier: NCT03336450
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

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.

Condition or disease Intervention/treatment Phase
Nervous System Diseases Drug: SHP615 Drug: MHOS/SHP615 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : November 27, 2019
Estimated Study Completion Date : November 27, 2019


Arm Intervention/treatment
Experimental: SHP615
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
SHP615 oromucosal solution will be administered as a single age-specific dose (2.5, 5, 7.5 and 10 mg).
Other Names:
  • MHOS
  • Midazolam hydrochloride oromucosal solution

Drug: MHOS/SHP615
MHOS/SHP615




Primary Outcome Measures :
  1. Percentage of Participants with Therapeutic Success [ Time Frame: From start of study drug administration up to 30 minutes (min) post-dose ]
    Therapeutic success will be 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.


Secondary Outcome Measures :
  1. Percentage of Participants Whose Seizure Event(s) Stopped Within 10 Minutes After Administration of MHOS/SHP615 and Who Have Sustained Absence of Seizure Activity for At least 1 Hour [ Time Frame: From start of study drug administration up to 1 hour (h) post-dose ]
    Percentage of participants whose seizure event stopped within 10 mins of single dose administration of SHP615 and who have sustained absence of seizure activity for at least 1 h will be evaluated.

  2. Percentage of Participants Whose Seizure Event(s) Stopped Within 10 Minutes After Administration of MHOS/SHP615 and who Have Sustained Absence of Seizure Activity for At least 4 Hours [ Time Frame: From start of study drug administration up to 4 h post-dose ]
    Percentage of participants whose seizure event stopped within 10 mins of single dose administration of SHP615 and who have sustained absence of seizure activity for at least 4 h will be evaluated.

  3. Percentage of Participants Whose Seizure Event(s) Stopped Within 10 Minutes After Administration of MHOS/SHP615 and Who Have Sustained Absence of Seizure Activity for At least 6 Hours [ Time Frame: From start of study drug administration up to 6 h post-dose ]
    Percentage of participants whose seizure event stopped within 10 mins of single dose administration of SHP615 and who have sustained absence of seizure activity for at least 6 h will be evaluated.

  4. Time to Resolution of Seizures (Convulsions) [ Time Frame: From start of study drug administration until resolution of seizure ]
    Time taken for the resolution of seizures after the administration of MHOS/SHP615 will be assessed.

  5. Time to Recovery of Consciousness/Baseline Mental Status [ Time Frame: From start of study drug administration until recovery of consciousness ]
    Time taken for the recovery of consciousness after the administration of MHOS/SHP615 will be assessed.

  6. Percentage of Participants Who Require Additional Anticonvulsant Medication for Ongoing SE 10 Minutes After Administration of MHOS/SHP615 [ Time Frame: 10 min post-dose ]
    Percentage of participants who require additional anticonvulsant medication for ongoing SE according to the participating hospital protocol or guideline, 10 minutes after the administration of MHOS/SHP615 will be assessed.

  7. Percentage of Participants Who Fail to Respond to Treatment [ Time Frame: 10 min post-dose ]
    Treatment failure/Nonresponder is defined as continuing seizure activity and/or the need for any additional rescue medication according to the participating healthcare setting protocol or guideline 10 minutes after administration of MHOS/SHP615

  8. Respiratory Depression [ Time Frame: 30 min, 1, 4, 6 and 24 h post-dose ]
    • Persistent decrease in oxygen saturation to <92% measured at 1, 4, 6, and 24 hours post dose (ie, <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).
    • Increase in respiratory effort such that assisted ventilation is used (bag-valve-mask ventilation or endotracheal intubation).

  9. Aspiration Pneumonia [ Time Frame: From start of study drug administration up to 24 h post-dose ]
    Diagnosis of aspiration pneumonia after single dose administration of SHP615.

  10. Sedation or Agitation as Measured by the Riker Sedation-Agitation Scale [ Time Frame: 30 min, 1, 4, 6 and 24 h post-dose ]
    Riker Sedation-Agitation Scale is a arousal/sedation tool ranging from 1 (unarousable condition) to 7 (Dangerous agitation).

  11. Occurrence of Buccal Irritation [ Time Frame: 1, 4 and 6 h post-dose ]
    Buccal cavity will be examined for redness, inflammation and ulceration and the occurrence of buccal irritation will be assessed.

  12. Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From start of study drug administration up to Week 1 ]
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of investigational product.

  13. Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event [ Time Frame: From start of study drug administration up to 24 h post-dose ]
    A change in the value of vital sign assessment can represent an AE if the change is clinically relevant or if, during treatment with the investigational product, a shift of a parameter is observed from a normal value to an abnormal value, or a further worsening of an already abnormal value.

  14. Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event [ Time Frame: From start of study drug administration up to 24 h post-dose ]
    Clinical laboratory (serum biochemistry and urinalysis) results out-of-range will be assessed and if they are clinically significant will be reported as AEs.

  15. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as an Adverse Event [ Time Frame: From start of study drug administration up to 24 h post-dose ]
    12-lead ECG will be performed. Any clinically significant change in ECG assessment will be reported as AE

  16. Oxygen Saturation [ Time Frame: 30 min, 1, 4, 6 and 24 h post-dose ]
    Oxygen saturation will be measured and recorded on room air. The investigator will record the oxygen saturation as well as the oxygen delivery system and amount of oxygen administered, if required



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 216 Months   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03336450


Contacts
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Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
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Japan
Yamanashi Prefectural Central Hospital Not yet recruiting
Kofu, Fujimi, Japan, 400-8506
Contact: Takuaki Oba       t-oba@epsogo.co.jp   
Principal Investigator: Yusuke Goto         
Hokkaido University Hospital Not yet recruiting
Sapporo, Hokkaido, Japan, 060-8648
Contact: Chika Holloway       holloway@huhp.hokudai.ac.jp   
Principal Investigator: Hideaki Shiraishi         
NHO Minami-Okayama Medical Center Not yet recruiting
Okayama, Okayama Prefecture, Japan, 701-0304
Contact: Miyuzu Taniguchi       taniguchi.miyuzu@nagasaki-mc.com   
Principal Investigator: Harumi Yoshinaga         
Tokyo Women's Medical University Yachiyo Medical Center Not yet recruiting
Yachiyo, Owada Shinden, Japan, 276-8524
Contact: Juri Obata       juri-obata@irom.co.jp   
Principal Investigator: Junichi Takanashi         
Shizuoka Institute of Epilepsy and Neurological Disorders Not yet recruiting
Shizuoka, Shizuoka Prefecture, Japan, 420-8688
Contact: Yoshiaki Yamamoto       yamamoty@shizuokamind.org   
Principal Investigator: Asako Horino         
Fukuoka Children's Hospital(NW) Not yet recruiting
Fukuoka, Japan, 813-0017
Contact: Shino Ohmura       s-ohmura@epsogo.co.jp   
Principal Investigator: Ryutaro Kira         
Gifu Prefectural General Medical Center Not yet recruiting
Gifu, Japan, 500-8717
Contact: Mayumi Sasada       sasada.mayumi@neues.co.jp   
Principal Investigator: Atsushi Imamura         
NHO Hokkaido Medical Center Not yet recruiting
Hokkaidō, Japan, 063-0005
Contact: Yoshiyuki Hori       horiyel@hok-mc.hosp.go.jp   
Principal Investigator: Masayoshi Nagao         
Kumamoto Saishunso National Hospital Not yet recruiting
Kumamoto, Japan, 861-1196
Contact: Akiko Nishioka       anishioka@saisyunsou1.hosp.go.jp   
Principal Investigator: Chizuru Ikeda         
NHO Nagasaki Medical Center Not yet recruiting
Nagasaki, Japan, 856-8562
Contact: Miyuzu Taniguchi       taniguchi.miyuzu@nagasaki-mc.com   
Principal Investigator: Shigeki Tanaka         
NHO Nishi Niigata Chuo National Hospital Not yet recruiting
Niigata, Japan, 950-2085
Contact: Emi Takahashi       chiken-kango01@masa.go.jp   
Principal Investigator: Jun Tohyama         
Aichi Children's Health and Medical Center(NW) Not yet recruiting
Obu, Japan, 474-8710
Contact: Yukiko Sone       sone.yukiko@e-smo.co.jp   
Principal Investigator: Kazuya Itomi         
Okayama University Hospital Not yet recruiting
Okayama, Japan, 700-0914
Contact: Hiroto Okuda       okuda-h@cc.okayama-u.ac.jp   
Principal Investigator: Katsuhiro Kobayashi         
Nakano Children's Hospital Not yet recruiting
Osaka, Japan, 535-0022
Contact: Atsuko Nakata       at-nakata@epsogo.co.jp   
Principal Investigator: Kiyotaka Murakami         
Osaka Women's and Children's Hospital(NW) Not yet recruiting
Osaka, Japan, 594-1101
Contact: Michiko Yamazaki       michiko@mch.pref.osaka.jp   
Principal Investigator: Yasuhiro Suzuki         
Jichi Children's Medical Center Tochigi Not yet recruiting
Saitama-shi, Japan, 330-8503
Contact: Kuniko Suzuki       ksuzuki@jichi.ac.jp   
Principal Investigator: Hitoshi Osaka         
Saitama Children's Medical Center(NW) Not yet recruiting
Saitama, Japan, 330-8777
Contact: Mika Arai       mk-arai@epsogo.co.jp   
Principal Investigator: Shinichiro Hamano         
Osaka University Hospital Not yet recruiting
Suita, Japan, 565-0871
Contact: Nozomi Okuda       okuda.nozomi@neues.co.jp   
Principal Investigator: Haruo Shintaku         
Tokyo Women's Medical University Hospital Not yet recruiting
Tokyo, Japan, 162-8666
Contact: Keiko Sato       keiko.yagi@miraca.com   
Principal Investigator: Hirokazu Oguni         
National Center Hospital, NCNP Recruiting
Tokyo, Japan, 187-0031
Contact: Naoya Gogun       irb-office@ncnp.go.jp   
Principal Investigator: Eiji Nakagawa         
Tottori University Hospital Not yet recruiting
Tottori, Japan, 683-8504
Contact: Yoshihiro Maegaki         
Principal Investigator: Yoshihiro Maegaki         
Osaka University Hospital Not yet recruiting
Yamadaoka, Japan, 565-0871
Contact: Miyuki Takamura       miyuki-takamura@ocrcn.or.jp   
Principal Investigator: Kuriko Shimono         
Kanagawa Children's Medical Center(NW) Not yet recruiting
Yokohama, Japan, 232-0066
Contact: Emiko Miura       emiura@kcmc.jp   
Principal Investigator: Tomohide Goto         
Sponsors and Collaborators
Shire
Investigators
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Study Director: Shire Director Shire

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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03336450     History of Changes
Other Study ID Numbers: SHP615-302
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Status Epilepticus
Midazolam
Nervous System Diseases
Seizures
Neurologic Manifestations
Signs and Symptoms
Pharmaceutical Solutions
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action