NCT03336645CompletedPhase 3
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
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Shire
- Enrollment
- 25
- Locations
- 22
- Primary Endpoint
- Percentage of Participants With Response Rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 3 Months to 216 Months (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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) 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.
Arms & Interventions
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.
Intervention: SHP615 (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Response Rate
Time Frame: 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.
Secondary Outcomes
- Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of SHP615 in Plasma(Pre-dose, 1, 3, and 6 hours post-dose)
- Number of Participants With Time to Recovery of Consciousness(From start of study drug administration up to follow-up (Day 8))
- Time at Maximum Concentration (Tmax) of SHP615 in Plasma(1, 3, and 6 hours post-dose)
- Elimination Half-life (T1/2) of SHP615 in Plasma(1, 3, and 6 hours post-dose)
- Percentage of Participants Who Failed to Respond to the Treatment With SHP615(10 minutes post-dose)
- Maximum Plasma Concentration (Cmax) of SHP615(1, 3, 6 hours post-dose)
- Area Under the Concentration-time Curve From Time Zero to 10 Minutes (AUC0-10) of SHP615 in Plasma(Pre-dose, 10 minutes post-dose)
- Percentage 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)
- Number of Participants With Time to Resolution of Seizures (Convulsions)(From start of study drug administration up to follow-up (Day 8))
- Concentration of SHP615 in Plasma at 10 Minutes (C10)(10 minutes post-dose)
- Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE)(10 minutes post-dose)
- Area Under the Concentration-time Curve From Time Zero to 180 Minutes (AUC0-180) of SHP615 in Plasma(Pre-dose, 180 minutes post-dose)
- Area Under the Concentration-time Curve From Time Zero to 60 Minutes (AUC0-60) of SHP615 in Plasma(Pre-dose, 60 minutes post-dose)
- Change From Baseline in Riker Sedation-Agitation Scale at 24 Hours Post-dose(Baseline, 24 hours post-dose)
- Change From Baseline in Oxygen Saturation Percentage at 24 Hours Post-dose(Baseline, 24 hours post-dose)
- Number of Participants With Respiratory Depression(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)(From start of study drug administration up to follow-up (Day 8))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (Day 8))
Investigators
Study Sites (22)
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