Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03336645
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : July 9, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

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.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Open-label Study to Determine the Efficacy, Safety, and Pharmacokinetics of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in the Hospital or Emergency Room
Actual Study Start Date : November 27, 2017
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:
  • Midazolam hydrochloride oromucosal solution
  • MHOS




Primary Outcome Measures :
  1. Percentage of Participants With Therapeutic Success [ Time Frame: From start of study drug administration up to 30 minutes (mins) postdose ]
    Therapeutic success will be defined as the cessation of visible seizure activity within 10 minutes (mins) with a sustained absence of visible seizure activity for 30 minutes following a single dose of SHP615.


Secondary Outcome Measures :
  1. Percentage of Participants Whose Seizure Event Stopped Within 10 Minutes of Single Dose of 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 h postdose ]
    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 Stopped Within 10 Minutes of Single Dose of 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 postdose ]
    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 Stopped Within 10 Minutes of Single Dose of 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 postdose ]
    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 to resolution of seizures (convulsions) from the administration of SHP615.

  5. Time to Recovery of Consciousness [ Time Frame: From start of study drug administration until recovery of consciousness ]
    Time to recovery of consciousness from the administration of SHP615.

  6. Percentage of Participants who Require Additional Anticonvulsant Medication for Ongoing status epilepticus (SE) 10 Minutes After Single Dose Administration of SHP615 [ Time Frame: 10 mins postdose ]
    Percentage of participants who require additional anticonvulsant medication for ongoing SE according to the participating healthcare setting protocol or guideline, 10 mins after a single dose of SHP615.

  7. Percentage of Participants who Fail to Respond to Treatment [ Time Frame: 10 mins postdose ]
    Treatment failure or 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 mins after a single dose of SHP615.

  8. Respiratory Depression [ Time Frame: Baseline up to 4 h postdose ]
    Persistent decrease in oxygen saturation to <92% measured at 10 minutes, 30 minutes, and 4, 6, and 24 hours postdose (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]).

  9. Aspiration Pneumonia [ Time Frame: Baseline up to 24 h postdose ]
    Diagnosis of aspiration pneumonia after single dose administration of SHP615.

  10. Sedation or Agitation as Measured by Riker Sedation-Agitation Scale [ Time Frame: Baseline, 0, 10 and 30 mins, 1, 4, 6 and 24 h postdose ]
    Riker Sedation-Agitation Scale is a arousal/sedation tool ranging from 1 (unarousable condition) to 7 (Dangerous agitation).

  11. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 24 h postdose ]
    An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant 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.

  12. Number of Participants With Clinically Significant Change in Vital Signs Reported as an Adverse Event [ Time Frame: Baseline up to 24 h postdose ]
    Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. 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.

  13. Number of Participants With Clinically Significant Change in Clinical Laboratory Results Reported as an Adverse Event (AE) [ Time Frame: Baseline up to Week 1 ]
    Clinical laboratory (serum biochemistry and urinalysis) results out-of-range will be assessed and if they are clinically significant will be reported as AEs.

  14. Measurement of Oxygen Saturation [ Time Frame: Baseline, 10 and 30 mins, 4, 6 and 24 h postdose ]
    Oxygen saturation at baseline 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.

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

  16. Occurrence of Buccal Irritation [ Time Frame: 1, 4 and 6 h postdose ]
    Buccal cavity will be examined for redness, inflammation, and ulceration.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Months to 216 Months   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03336645


Contacts
Layout table for location contacts
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Locations
Layout table for location information
Japan
Yamanashi Prefectural Central Hospital Recruiting
Kofu, Fujimi, Japan, 400-8506
Contact: Takuaki Oba       t-oba@epsogo.co.jp   
Principal Investigator: Yusuke Goto         
Gifu Prefectural General Medical Center Recruiting
Gifu, Gifu Prefecture, Japan, 500-8717
Contact: Mayumi Sasada       sasada.mayumi@neues.co.jp   
Principal Investigator: Atsushi Imamura         
Hokkaido University Hospital Recruiting
Sapporo, Hokkaido, Japan, 060-8648
Contact: Chika Holloway       holloway@huhp.hokudai.ac.jp   
Principal Investigator: Hideaki Shiraishi         
Tokyo Women's Medical University Hospital Not yet recruiting
Tokyo, Kawadacho, Japan, 162-8666
Contact: Keiko Sato       keiko.yagi@miraca.com   
Principal Investigator: Hirokazu Oguni         
NHO Minami-Okayama Medical Center 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         
Jichi Children's Medical Center Tochigi Not yet recruiting
Saitama-shi, Saitama-ken, Japan, 330-8503
Contact: Kuniko Suzuki       ksuzuki@jichi.ac.jp   
Principal Investigator: Hitoshi Osaka         
Shizuoka Institute of Epilepsy and Neurological Disorders Recruiting
Shizuoka, Shizuoka Prefecture, Japan, 420-8688
Contact: Yoshiaki Yamamoto       yamamoty@shizuokamind.org   
Principal Investigator: Asako Horino         
Fukuoka Children's Hospital(NW) Recruiting
Fukuoka, Japan, 813-0017
Contact: Shino Ohmura       s-ohmura@epsogo.co.jp   
Principal Investigator: Ryutaro Kira         
NHO Hokkaido Medical Center Recruiting
Hokkaidō, Japan, 063-0005
Contact: Yoshiyuki Hori       horiyel@hok-mc.hosp.go.jp   
Principal Investigator: Masayoshi Nagao         
Kumamoto Saishunso National Hospital Recruiting
Kumamoto, Japan, 861-1196
Contact: Akiko Nishioka       anishioka@saisyunsou1.hosp.go.jp   
Principal Investigator: Chizuru Ikeda         
NHO Nagasaki Medical Center Recruiting
Nagasaki, Japan, 856-8562
Contact: Miyuzu Taniguchi       taniguchi.miyuzu@nagasaki-mc.com   
Principal Investigator: Shigeki Tanaka         
NHO Nishi Niigata Chuo National Hospital 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) Recruiting
Osaka, Japan, 594-1101
Contact: Michiko Yamazaki       michiko@mch.pref.osaka.jp   
Principal Investigator: Yasuhiro Suzuki         
Saitama Children's Medical Center(NW) Recruiting
Saitama, Japan, 330-8777
Contact: Mika Arai       mk-arai@epsogo.co.jp   
Principal Investigator: Shinichiro Hamano         
Osaka University Hospital Recruiting
Suita, Japan, 565-0871
Contact: Nozomi Okuda       okuda.nozomi@neues.co.jp   
Principal Investigator: Haruo Shintaku         
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
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) Recruiting
Yokohama, Japan, 232-0066
Contact: Emiko Miura       emiura@kcmc.jp   
Principal Investigator: Tomohide Goto         
Sponsors and Collaborators
Shire
Investigators
Layout table for investigator information
Study Director: Shire Study Physician Shire

Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03336645     History of Changes
Other Study ID Numbers: SHP615-301
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: July 9, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shire:
Seizure
Midazolam hydrochloride
Convulsive
Additional relevant MeSH terms:
Layout table for MeSH terms
Status Epilepticus
Nervous System Diseases
Seizures
Neurologic Manifestations
Signs and Symptoms
Midazolam
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