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

15 juillet 2020 mis à jour par: Shire

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

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

25

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Japon
      • Fukuoka, Japon, 813-0017
        • Fukuoka Children's Hospital(NW)
      • Hokkaidō, Japon, 063-0005
        • NHO Hokkaido Medical Center
      • Kumamoto, Japon, 861-1196
        • Kumamoto Saishunso National Hospital
      • Nagasaki, Japon, 856-8562
        • NHO Nagasaki Medical Center
      • Niigata, Japon, 950-2085
        • NHO Nishi Niigata Chuo National Hospital
      • Obu, Japon, 474-8710
        • Aichi Children's Health and Medical Center(NW)
      • Okayama, Japon, 700-0914
        • Okayama University Hospital
      • Osaka, Japon, 535-0022
        • Nakano Children's Hospital
      • Osaka, Japon, 594-1101
        • Osaka Women's and Children's Hospital(NW)
      • Saitama, Japon, 330-8777
        • Saitama Children's Medical Center(NW)
      • Suita, Japon, 565-0871
        • Osaka University Hospital
      • Tokyo, Japon, 187-0031
        • National Center Hospital, NCNP
      • Tottori, Japon, 683-8504
        • Tottori University Hospital
      • Yamadaoka, Japon, 565-0871
        • Osaka University Hospital
      • Yokohama, Japon, 232-0066
        • Kanagawa Children's Medical Center(NW)
    • Fujimi
      • Kofu, Fujimi, Japon, 400-8506
        • Yamanashi Prefectural Central Hospital
    • Gifu Prefecture
      • Gifu, Gifu Prefecture, Japon, 500-8717
        • Gifu Prefectural General Medical Center
    • Hokkaido
      • Sapporo, Hokkaido, Japon, 060-8648
        • Hokkaido University Hospital
    • Kawadacho
      • Tokyo, Kawadacho, Japon, 162-8666
        • Tokyo Women's Medical University Hospital
    • Okayama Prefecture
      • Okayama, Okayama Prefecture, Japon, 701-0304
        • NHO Minami-Okayama Medical Center
    • Owada Shinden
      • Yachiyo, Owada Shinden, Japon, 276-8524
        • Tokyo Women's Medical University Yachiyo Medical Center
    • Saitama-ken
      • Saitama-shi, Saitama-ken, Japon, 330-8503
        • Jichi Children's Medical Center Tochigi
    • Shizuoka Prefecture
      • Shizuoka, Shizuoka Prefecture, Japon, 420-8688
        • Shizuoka Institute of Epilepsy and Neurological Disorders

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

3 mois à 18 ans (Enfant, Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: SHP615
La solution buccale SHP615 sera administrée en une seule dose spécifique à l'âge (2,5, 5, 7,5 et 10 mg).
Autres noms:
  • MHOS
  • Solution buccale de chlorhydrate de midazolam

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants With Response Rate
Délai: From start of study drug administration up to 30 minutes post-dose
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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4 and 6 Hours
Délai: From start of study drug administration up to 1, 4 and 6 hours post-dose
Percentage of participants whose seizure event stopped within 10 minutes of single dose administration of SHP615 and who had sustained absence of seizure activity for at least 1, 4, and 6 hours were reported.
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)
Délai: From start of study drug administration up to follow-up (Day 8)
Time to resolution of seizures (convulsions) was calculated as time from IP administration to the end of the initial seizure or administration of rescue anti-convulsant medication, whichever occurs first. Initial seizure referred to the seizure that triggered the use of the IP. Number of participants with time to resolution of seizures (convulsions) from the administration of SHP615 were reported.
From start of study drug administration up to follow-up (Day 8)
Number of Participants With Time to Recovery of Consciousness
Délai: From start of study drug administration up to follow-up (Day 8)
Time to recovery of consciousness (in minutes) was calculated only for participants who lost consciousness pre-dose at time from investigational product administration to recovery of consciousness post-dose or administration of rescue anticonvulsant medication, whichever occurs first. Number of participants with time to recovery of consciousness were reported.
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)
Délai: 10 minutes post-dose
Percentage of participants who required additional anticonvulsant medication for ongoing SE, 10 minutes after a single dose of SHP615 were reported.
10 minutes post-dose
Percentage of Participants Who Failed to Respond to the Treatment With SHP615
Délai: 10 minutes post-dose
Treatment failure/non-responder was defined as participants with continuing seizure activity and/or the need for any additional rescue medication according to the participating healthcare setting protocol or guideline, for 10 mins or more after a single dose of the IP.
10 minutes post-dose
Concentration of SHP615 in Plasma at 10 Minutes (C10)
Délai: 10 minutes post-dose
Concentration of SHP615 in plasma at 10 minutes were reported.
10 minutes post-dose
Maximum Plasma Concentration (Cmax) of SHP615
Délai: 1, 3, 6 hours post-dose
Cmax of SHP615 in plasma were reported.
1, 3, 6 hours post-dose
Area Under the Concentration-time Curve From Time Zero to 10 Minutes (AUC0-10) of SHP615 in Plasma
Délai: Pre-dose, 10 minutes post-dose
AUC0-10 of SHP615 in plasma were reported. Here "min ng/mL" was minutes nanogram per milliliter.
Pre-dose, 10 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to 60 Minutes (AUC0-60) of SHP615 in Plasma
Délai: Pre-dose, 60 minutes post-dose
AUC0-60 of SHP615 in plasma were reported.
Pre-dose, 60 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to 180 Minutes (AUC0-180) of SHP615 in Plasma
Délai: Pre-dose, 180 minutes post-dose
AUC0-180 of SHP615 in plasma were reported.
Pre-dose, 180 minutes post-dose
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of SHP615 in Plasma
Délai: Pre-dose, 1, 3, and 6 hours post-dose
AUC(0-infinity) of SHP615 in plasma were reported.
Pre-dose, 1, 3, and 6 hours post-dose
Time at Maximum Concentration (Tmax) of SHP615 in Plasma
Délai: 1, 3, and 6 hours post-dose
Tmax of SHP615 in plasma were reported.
1, 3, and 6 hours post-dose
Elimination Half-life (T1/2) of SHP615 in Plasma
Délai: 1, 3, and 6 hours post-dose
T1/2 of SHP615 in plasma were reported.
1, 3, and 6 hours post-dose
Number of Participants With Respiratory Depression
Délai: From start of study drug administration up to follow-up (Day 8)
Respiratory depression, included the following measures within 24 hours after administration of the IP: i) Persistent decrease in oxygen saturation to < 92 percent (%) measured at 10, 30 minutes, and 4, 6, and 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.
From start of study drug administration up to follow-up (Day 8)
Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)
Délai: From start of study drug administration up to follow-up (Day 8)
TEAEs was 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 IP. Number of participants with aspiration pneumonia identified as TEAEs were reported.
From start of study drug administration up to follow-up (Day 8)
Change From Baseline in Riker Sedation-Agitation Scale at 24 Hours Post-dose
Délai: Baseline, 24 hours post-dose
Sedation-Agitation was assessed, using the "Riker Sedation-Agitation Scale" (SAS) by the following 7-point scale: 7. dangerous agitation; 6. very agitated; 5. agitated; 4. calm, cooperative; 3. sedated; 2. very sedated; 1. unarousable. Change from baseline in riker sedation-agition scale at 24 hours post-dose were reported.
Baseline, 24 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Délai: From start of study drug administration up to follow-up (Day 8)
An adverse event (AE) was 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 was 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 IP. Number of participants with TEAEs were reported.
From start of study drug administration up to follow-up (Day 8)
Change From Baseline in Oxygen Saturation Percentage at 24 Hours Post-dose
Délai: Baseline, 24 hours post-dose
Oxygen saturation at baseline was measured and recorded on room air. The investigator had recorded the oxygen saturation, oxygen delivery system and amount of oxygen administered during the study. Change from baseline in oxygen saturation percentage at 24 hours post-dose were reported.
Baseline, 24 hours post-dose

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Shire

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

23 octobre 2017

Achèvement primaire (Réel)

19 août 2019

Achèvement de l'étude (Réel)

19 août 2019

Dates d'inscription aux études

Première soumission

6 novembre 2017

Première soumission répondant aux critères de contrôle qualité

6 novembre 2017

Première publication (Réel)

8 novembre 2017

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

31 juillet 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

15 juillet 2020

Dernière vérification

1 juin 2020

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • SHP615-301

Plan pour les données individuelles des participants (IPD)

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OUI

Description du régime IPD

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.

Critères d'accès au partage IPD

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.

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE
  • CIF
  • RSE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

Essais cliniques sur SHP615

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