Study of Midazolam Hydrochloride Oromucosal Solution (MHOS/SHP615) in Pediatric Patients With Status Epilepticus (Convulsive) in the Community Setting

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.

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 (cessation of seizure within 10 minutes with sustained absence of seizure for 30 minutes) performed after the administration of IP.

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.

Time frame: Up to 24 hours post-dose

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

Number 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 (cessation of seizure within 10 minutes with sustained absence of seizure for 30 minutes) performed after the administration of IP.

Treatment failure/non-responder was defined as continuing seizure activity and/or the need for any additional rescue medication according to the participating healthcare setting protocol or guideline 10 minutes after administration of SHP615 was 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 (cessation of seizure within 10 minutes with sustained absence of seizure for 30 minutes) performed after the administration of IP.

Percentage of participants who required additional anticonvulsant medication for ongoing SE according to the participating hospital protocol or guideline, 10 minutes after the administration 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 (cessation of seizure within 10 minutes with sustained absence of seizure for 30 minutes) performed after the administration of IP.

Time to recovery of consciousness in minutes was calculated only for participants who lost consciousness pre-dose as time from SHP615 administration to recovery of consciousness post-dose or administration of rescue anticonvulsant medication, whichever occurs first. Participant wise data was reported for this outcome.

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 (cessation of seizure within 10 minutes with sustained absence of seizure for 30 minutes) performed after the administration of IP. Here, number analyzed signifies participants who were evaluable for this specific category.

Time to resolution of seizures (convulsions) was calculated as time from SHP615 administration to the end of the initial seizure or administration of rescue anticonvulsant medication, whichever occurs first. The initial seizure refers to the seizure which triggered the use of the IP. Participant wise data was reported for this outcome.

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 (cessation of seizure within 10 minutes with sustained absence of seizure for 30 minutes) performed after the administration of IP. Here, number analyzed signifies participants who were evaluable for this specific category.

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. Number of participants analyzed for sedation or agitation measured by the riker sedation-agitation scale were reported.

Time frame: 1, 4, 6, and 24 hours post-dose

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

TEAEs was defined as adverse events (AEs) whose onset occurs, severity worsens or intensity increases on or after the date of SHP615 administration. 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 IP, regardless of whether the study drug administration was documented to be complete or not on the study drug administration eCRF.

TEAEs was defined as AEs whose onset occurs, severity worsens or intensity increases on or after the date of IP administration. Buccal cavity was examined for redness, inflammation and ulceration. Number of participants with buccal irritation reported as TEAEs were reported.

Time frame: Up to 6 hours post-dose

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

Clinical laboratory evaluations included biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory abnormalities which were deemed clinically significant by the investigator were recorded as TEAEs.

Time frame: From start of study drug administration up to 24 hours post-dose

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

12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAEs.

Time frame: From start of study drug administration up to 24 hours post-dose

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

Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAEs.

Time frame: From start of study drug administration up to 24 hours post-dose

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

An 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 whose onset occurs, severity worsens or intensity increases on or after the date of IP administration. 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 IP, regardless of whether the study drug administration was documented to be complete or not on the study drug administration eCRF.

Oxygen saturation is the amount of oxygen that is in bloodstream and is measured as the percentage of blood hemoglobin that is carrying oxygen. Normal oxygen saturation levels are considered to be 95-100 percent; low oxygen saturation values indicate worse disease. Oxygen saturation was measured and recorded on room air. The investigator recorded the oxygen saturation as well as the oxygen delivery system and amount of oxygen administered during hospital setting. Percentage of participants with normal oxygen saturation values collected during hospital setting were reported.

Time frame: 0.5, 1, 4, 6 and 24 hours post-dose

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