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

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.

Time frame: From start of study drug administration up to 30 minutes post-dose

Population: Full Analysis Set (FAS) consisted of all participants in the safety set who had at least 1 assessment for determination of therapeutic success (date and time of the IP administration and seizure cessation for the initial seizure; participants with no recurrence of seizure within 30 minutes post-dose) performed after the administration of the IP.

AUC0-10 of SHP615 in plasma were reported. Here min ng/mL was minutes nanogram per milliliter.

Time frame: Pre-dose, 10 minutes post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

AUC0-180 of SHP615 in plasma were reported.

Time frame: Pre-dose, 180 minutes post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

AUC0-60 of SHP615 in plasma were reported.

Time frame: Pre-dose, 60 minutes post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

AUC(0-infinity) of SHP615 in plasma were reported.

Time frame: Pre-dose, 1, 3, and 6 hours post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

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.

Time frame: Baseline, 24 hours post-dose

Population: Safety set consisted of all participants who had received a single dose of the IP, regardless of whether IP administration was documented to be complete or not on the IP administration page of the eCRF. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

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.

Time frame: Baseline, 24 hours post-dose

Population: Safety set consisted of all participants who had received a single dose of the IP, regardless of whether IP administration was documented to be complete or not on the IP administration page of the eCRF. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

Concentration of SHP615 in plasma at 10 minutes were reported.

Time frame: 10 minutes post-dose

Population: Pharmacokinetic (PK) set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

T1/2 of SHP615 in plasma were reported.

Time frame: 1, 3, and 6 hours post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

Cmax of SHP615 in plasma were reported.

Time frame: 1, 3, 6 hours post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.

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.

Time frame: From start of study drug administration up to follow-up (Day 8)

Population: Safety set consisted of all participants who had received a single dose of the IP, regardless of whether IP administration was documented to be complete or not on the IP administration page of the eCRF.

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.

Time frame: From start of study drug administration up to follow-up (Day 8)

Population: Safety set consisted of all participants who had received a single dose of the IP, regardless of whether IP administration was documented to be complete or not on the IP administration page of the eCRF.

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.

Time frame: From start of study drug administration up to follow-up (Day 8)

Population: FAS consisted of all participants in the safety set who had at least 1 assessment for determination of therapeutic success (date and time of the IP administration and seizure cessation for the initial seizure; participants with no recurrence of seizure within 30 minutes post-dose) performed after the administration of the IP.

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.

Time frame: From start of study drug administration up to follow-up (Day 8)

Population: FAS consisted of all participants in the safety set who had at least 1 assessment for determination of therapeutic success (date and time of the IP administration and seizure cessation for the initial seizure; participants with no recurrence of seizure within 30 minutes post-dose) performed after the administration of the IP.

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.

Time frame: From start of study drug administration up to follow-up (Day 8)

Population: Safety set consisted of all participants who had received a single dose of the IP, regardless of whether IP administration was documented to be complete or not on the IP administration page of the eCRF.

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.

Time frame: 10 minutes post-dose

Population: FAS consisted of all participants in the safety set who had at least 1 assessment for determination of therapeutic success (date and time of the IP administration and seizure cessation for the initial seizure; participants with no recurrence of seizure within 30 minutes post-dose) performed after the administration of the IP.

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.

Time frame: From start of study drug administration up to 1, 4 and 6 hours post-dose

Population: FAS consisted of all participants in the safety set who had at least 1 assessment for determination of therapeutic success (date and time of the IP administration and seizure cessation for the initial seizure; participants with no recurrence of seizure within 30 minutes post-dose) performed after the administration of the IP.

Percentage of participants who required additional anticonvulsant medication for ongoing SE, 10 minutes after a single dose of SHP615 were reported.

Time frame: 10 minutes post-dose

Population: FAS consisted of all participants in the safety set who had at least 1 assessment for determination of therapeutic success (date and time of the IP administration and seizure cessation for the initial seizure; participants with no recurrence of seizure within 30 minutes post-dose) performed after the administration of the IP.

Tmax of SHP615 in plasma were reported.

Time frame: 1, 3, and 6 hours post-dose

Population: PK set consisted of all participants who received a single dose of the IP and for whom at least 1 PK blood sample was collected post-dose. Here, the number of participants analyzed refer to the participants evaluable for this outcome.