A Phase 3, Multicenter, Open-label Extension Study of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in Community Settings
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 3
- 试验地点
- 22
- 主要终点
- Efficacy: Number of Participants With Therapeutic Success
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 216 Months（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/SHP
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: SHP615 (Drug)
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.
干预措施: MHOS/SHP615 (Drug)
结局指标
主要结局
Efficacy: Number of Participants With Therapeutic Success
时间窗: From start of study drug administration up to 30 minutes post-dose
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.
Safety: Number of Participants With Respiratory Depression
时间窗: Up to 24 hours post-dose
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.
次要结局
- 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 Recovery of Consciousness(From start of study drug administration up to follow-up (Day 8))
- Safety: Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (Day 8))
- Safety: Number of Participants With Clinically Significant Change in Vital Signs Reported as TEAEs(From start of study drug administration up to 24 hours post-dose)
- Safety: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as TEAEs(From start of study drug administration up to 24 hours post-dose)
- Efficacy: Time to Resolution of Seizures (Convulsions)(From start of study drug administration up to follow-up (Day 8))
- Safety: Number of Participants Analyzed for Sedation or Agitation Measured by the Riker Sedation-Agitation Scale(1, 4, 6, and 24 hours post-dose)
- Safety: Number of Participants With Buccal Irritation Reported as Treatment Emergent Adverse Events (TEAEs)(Up to 6 hours post-dose)
- Safety: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as TEAEs(From start of study drug administration up to 24 hours post-dose)
- Safety: Percentage of Participants With Normal Oxygen Saturation Values Collected During Hospital Setting(0.5, 1, 4, 6 and 24 hours post-dose)
- 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)
- Safety: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (Day 8))