Trial Outcomes & Findings for Efficacy and Safety of Diazepam in the Management of Refractory Epilepsy in Selected Patients Who Require Intermittent Medical Intervention for Acute Repetitive Seizures. (NCT NCT00319501)

NCT ID: NCT00319501

Last Updated: 2016-09-23

Results Overview

An event was defined as an episode of or required rescue medication for an episode of acute repetitive seizures (ARS) within 15 minutes to 12 hours following study drug administration. Patients without an ARS event were censored at 12 hours. Diaries were provided; if no diary was returned, or the diary did not provide answers to questions about seizures and rescue during the 12-hour follow-up period, the patient was considered censored as of 15 minutes past the treatment time, unless another contact was documented. If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the ARS episode. Patients and their caregivers were trained to recognize the onset of an episode of ARS and when and how to administer study drug.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

234 participants

Primary outcome timeframe

From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period

Results posted on

2016-09-23

Participant Flow

Of 234 participants randomized, 71 (29 placebo, 42 diazepam) did not receive/attempt to receive treatment. Discontinuation prior to treatment due to: 3,0 protocol violations; 6,5 sponsor's request; 4,8 Principal Investigator request; 5,11 other; 0,2 lost to follow-up, and 9,10 withdrawn consent.

Participant milestones

Participant milestones
Measure	Diazepam During the Double-blind Period, participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS). Additional doses were permissible as needed during the Open-label and Open-label Extension Periods.	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Double-blind Period STARTED	124	110
Double-blind Period Received Treatment	82	81
Double-blind Period COMPLETED	81	78
Double-blind Period NOT COMPLETED	43	32
Open-label Period STARTED	161	0
Open-label Period Received Treatment	128	0
Open-label Period COMPLETED	45	0
Open-label Period NOT COMPLETED	116	0
Open-label Extension Period STARTED	51	0
Open-label Extension Period Received Treatment	33	0
Open-label Extension Period COMPLETED	0	0
Open-label Extension Period NOT COMPLETED	51	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Diazepam During the Double-blind Period, participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS). Additional doses were permissible as needed during the Open-label and Open-label Extension Periods.	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Double-blind Period Withdrawal by Subject	0	3
Double-blind Period Sponsor Request	1	0
Double-blind Period Did not receive treatment	42	29
Open-label Period Adverse Event	5	0
Open-label Period Protocol Violation	6	0
Open-label Period Withdrawal by Subject	38	0
Open-label Period Principal Investigator decision	6	0
Open-label Period Sponsor request	12	0
Open-label Period Lost to Follow-up	5	0
Open-label Period Did not receive treatment	33	0
Open-label Period Other	11	0
Open-label Extension Period Adverse Event	2	0
Open-label Extension Period Did not receive treatment	18	0
Open-label Extension Period Other	1	0
Open-label Extension Period Principal investigator decision	2	0
Open-label Extension Period Sponsor request	26	0
Open-label Extension Period Withdrawal by Subject	2	0

Baseline Characteristics

Efficacy and Safety of Diazepam in the Management of Refractory Epilepsy in Selected Patients Who Require Intermittent Medical Intervention for Acute Repetitive Seizures.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Diazepam n=124 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS). Additional doses were permissible as needed during the Open-label and Open-label Extension Periods.	Placebo n=110 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.	Total n=234 Participants Total of all reporting groups
Age, Continuous	22.8 years STANDARD_DEVIATION 15.98 • n=5 Participants	21.3 years STANDARD_DEVIATION 12.92 • n=7 Participants	22.1 years STANDARD_DEVIATION 14.61 • n=5 Participants
Age, Customized 2 to 5 years	12 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants
Age, Customized 6 to 11 years	18 participants n=5 Participants	14 participants n=7 Participants	32 participants n=5 Participants
Age, Customized 12 years and older	94 participants n=5 Participants	90 participants n=7 Participants	184 participants n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	54 Participants n=7 Participants	116 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants	56 Participants n=7 Participants	118 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	109 Participants n=5 Participants	101 Participants n=7 Participants	210 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	104 Participants n=5 Participants	89 Participants n=7 Participants	193 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Place of Residence Home	123 Participants n=5 Participants	107 Participants n=7 Participants	230 Participants n=5 Participants
Place of Residence Foster home	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Place of Residence Group home	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Place of Residence Residential facility	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Place of Residence Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Height	154.2 Centimeters STANDARD_DEVIATION 25.08 • n=5 Participants	154.5 Centimeters STANDARD_DEVIATION 22.61 • n=7 Participants	154.4 Centimeters STANDARD_DEVIATION 23.91 • n=5 Participants
Weight	61.0 Kilograms STANDARD_DEVIATION 29.15 • n=5 Participants	58.9 Kilograms STANDARD_DEVIATION 28.47 • n=7 Participants	60.0 Kilograms STANDARD_DEVIATION 28.79 • n=5 Participants

PRIMARY outcome

Timeframe: From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Double-blind Period.

Outcome measures

Outcome measures
Measure	Diazepam n=82 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo n=81 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Time to Next Seizure or Rescue Medication During the Double-blind Period (Kaplan-Meier 50th Percentile)	5.92 Hours Interval 2.28 to NA=not available. Not estimable due to the low number of events in the arm	NA Hours NA=not available. Not estimable due to the low number of events in the arm

PRIMARY outcome

Timeframe: From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Open-label Period.

Outcome measures

Outcome measures
Measure	Diazepam n=129 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Percentage of Participants With an Event (Next Seizure or Rescue Medication) During the Open-label Period	22.4 Percentage of participants	—

SECONDARY outcome

Timeframe: From 15 minutes to 12 hours following study drug administration for an episode of ARS during the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS during the Double-blind Period.

If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the acute repetitive seizure (ARS) episode. Each patient's specific criteria for seizure and an episode of ARS were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug. An episode of ARS was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

Outcome measures

Outcome measures
Measure	Diazepam n=82 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo n=81 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Number of Participants Requiring Rescue Medication During the Double-blind Period	14 Participants	24 Participants

SECONDARY outcome

Timeframe: From 15 minutes to 12 hours following study drug administration for onset of an episode of ARS during the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an episode of ARS during the Double-blind Period.

Any use of emergency treatment (such as an emergency room visit) was recorded in the patient's diary, along with the date, time, and reason for the emergency treatment. Emergency department visits required some type of rescue action taken, other than the visit itself. An episode of acute repetitive seizures (ARS) was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

Outcome measures

Outcome measures
Measure	Diazepam n=82 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo n=81 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Number of Participants Requiring Emergency Department Visits During the Double-blind Period	2 Participants	4 Participants

SECONDARY outcome

Timeframe: From 15 minutes to 12 hours following study drug administration for an episode of ARS during the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Double-blind Period.

Other rescue medical care consisted of care other than rescue medication or emergency department visits. Each patient's specific criteria for seizure and an episode of acute repetitive seizure (ARS) were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug. An episode of ARS was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

Outcome measures

Outcome measures
Measure	Diazepam n=82 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo n=81 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Number of Participants Requiring Rescue Medical Care Other Than Rescue Medication or Emergency Department Visits During the Double-blind Period	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Assessments completed at the end of each treated episode of ARS in the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an episode of ARS during the Double-blind Period.

Caregiver global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes and is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) is defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

Outcome measures

Outcome measures
Measure	Diazepam n=79 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo n=78 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Mean Score on Caregiver Global Treatment Assessment During the Double-blind Period	6.2 Units on a scale Standard Deviation 2.79	5.5 Units on a scale Standard Deviation 2.86

SECONDARY outcome

Timeframe: At Visit 2 and subsequent visits in the Double-blind Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an episode of ARS during the Double-blind Period.

Physician global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes. The physician global evaluation is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

Outcome measures

Outcome measures
Measure	Diazepam n=81 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo n=78 Participants During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Mean Score on Physician Global Treatment Assessment During the Double-blind Period	6.3 Units on a scale Standard Deviation 2.45	5.5 Units on a scale Standard Deviation 2.69

SECONDARY outcome

Timeframe: From 15 minutes to 12 hours after study drug administration during the Open-label Period

Population: All randomized participants in whom an attempt (successful or not) was made to administer study drug for an ARS episode during the Open-label Period of the study.

Each patient's specific criteria for seizure and an episode of acute repetitive seizure (ARS) were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug. If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the ARS episode.

Outcome measures

Outcome measures
Measure	Diazepam n=129 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Number of Participants Requiring Rescue Medication During the Open-label Period	39 Participants	—

SECONDARY outcome

Timeframe: From 15 minutes to 12 hours after study drug administration for onset of an episode of ARS during the Open-label Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Open-label Period.

Outcome measures

Outcome measures
Measure	Diazepam n=129 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Number of Participants Requiring Emergency Department Visits During the Open-label Period	13 Participants	—

SECONDARY outcome

Timeframe: From 15 minutes to 12 hours after study drug administration for onset of an episode of ARS during the Open-label Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Double-blind Period.

Outcome measures

Outcome measures
Measure	Diazepam n=129 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Number of Participants Requiring Rescue Medical Care Other Than Medication or Emergency Department Visits During the Open-label Period	5 Participants	—

SECONDARY outcome

Timeframe: Assessments completed at the end of each treated episode of ARS in the Open-label Period

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Open-label Period and who were available for participation.

Outcome measures

Outcome measures
Measure	Diazepam n=124 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Mean Score on Caregiver Global Treatment Assessment During the Open-label Period	6.78 Units on a scale Standard Deviation 1.896	—

SECONDARY outcome

Timeframe: From Visit 2 and subsequent visits in the Open-label Period to discharge or study termination

Population: All randomized participants for whom an attempt (successful or not) was made to administer study drug for an ARS event during the Open-label Period and who were available for evaluation.

Physician global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes and is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) is defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

Outcome measures

Outcome measures
Measure	Diazepam n=124 Participants Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).	Placebo During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Mean Score on Physician Global Treatment Assessment During the Open-label Period	6.87 Units on a scale Standard Deviation 1.645	—

Adverse Events

Diazepam (Double-blind Period)

Serious events: 2 serious events

Other events: 33 other events

Deaths: 0 deaths

Diazepam (Open-label Period)

Serious events: 20 serious events

Other events: 43 other events

Deaths: 0 deaths

Diazepam (Open-label Extension)

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo (Double-blind Period)

Serious events: 3 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Diazepam (Double-blind Period) n=81 participants at risk Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.	Diazepam (Open-label Period) n=128 participants at risk Participants received an age- and weight-appropriate dose of placebo solution administered using a spring-driven, pressure-activated, prefilled autoinjector. Additional doses were permissible as needed.	Diazepam (Open-label Extension) n=33 participants at risk Participants continued to receive diazepam in an age- and weight-appropriate dose of administered using a spring-driven, pressure-activated, prefilled autoinjector. Additional doses were permissible as needed at the onset of an ARS episode. Participants were to continue until drug became marketed.	Placebo (Double-blind Period) n=79 participants at risk Participants received a single dose of diazepam-matching solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
General disorders GAIT DISTURBANCES	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations GASTROENTERITIS	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations Pneumonia	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations STAPHYLOCOCCAL BACTERAEMIA	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders EPILEPSY	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	7.8% 10/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	15.2% 5/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders HEADACHE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders LOSS OF CONSCIOUSNESS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders STATUS EPILEPTICUS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders POSTICTAL STATE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications FEMUR FRACTURE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications GASTROINTESTINAL STOMA COMPLICATION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications HEAT STROKE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications JAW FRACTURE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications CORNEAL ABRASION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications TOXICITY TO VARIOUS AGENTS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders AFFECTIVE DISORDER	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders ANXIETY DISORDER	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders DEPRESSION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders HALLUCINATION, AUDITORY	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders MENTAL STATUS CHANGES	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders PSYCHOTIC DISORDER	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders SUICIDAL IDEATION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Respiratory, thoracic and mediastinal disorders RESPIRATORY FAILURE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.6% 2/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Respiratory, thoracic and mediastinal disorders ACUTE RESPIRATORY FAILURE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Respiratory, thoracic and mediastinal disorders RESPIRATORY DISTRESS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders PYREXIA	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations SEPSIS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations SEPTIC SHOCK	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations APPENDICITIS PERFORATED	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations CELLULITIS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations CELLULITIS ORBITAL	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Infections and infestations HORDEOLUM	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Metabolism and nutrition disorders HYPOCALCAEMIA	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.78% 1/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Cardiac disorders ANGINA PECTORIS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Cardiac disorders ATRIAL FIBRILLATION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Cardiac disorders MYOCARDIAL INFARCTION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.

Other adverse events
Measure	Diazepam (Double-blind Period) n=81 participants at risk Participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, administered by caregivers untrained as and unsupervised by healthcare professionals. Drug was delivered by a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.	Diazepam (Open-label Period) n=128 participants at risk Participants received an age- and weight-appropriate dose of placebo solution administered using a spring-driven, pressure-activated, prefilled autoinjector. Additional doses were permissible as needed.	Diazepam (Open-label Extension) n=33 participants at risk Participants continued to receive diazepam in an age- and weight-appropriate dose of administered using a spring-driven, pressure-activated, prefilled autoinjector. Additional doses were permissible as needed at the onset of an ARS episode. Participants were to continue until drug became marketed.	Placebo (Double-blind Period) n=79 participants at risk Participants received a single dose of diazepam-matching solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Injury, poisoning and procedural complications FOOT FRACTURE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications HEAD INJURY	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications INCISION SITE PAIN	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications JOINT DISLOCATION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications JOINT INJURY	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE PAIN	17.3% 14/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	11.7% 15/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	6.1% 2/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	13.9% 11/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE HEMORRHAGE	4.9% 4/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	9.4% 12/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	6.3% 5/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE BRUISING	2.5% 2/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	6.2% 8/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	2.5% 2/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE SWELLING	2.5% 2/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	2.3% 3/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders PYREXIA	2.5% 2/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	7.0% 9/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	2.5% 2/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders ADVERSE DRUG REACTIONS	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders CHILLS	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders ENERGY INCREASED	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders FATIGUE	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.1% 4/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE ERYTHEMIA	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE LACERATION	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE REACTION	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE ANESTHESIA	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE DISCOMFORT	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE IRRITATION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
General disorders INJECTION SITE MASS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders HEADACHE	2.5% 2/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	17.2% 22/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	2.5% 2/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders DIZZINESS	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	5.5% 7/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	6.1% 2/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders EPILEPSY	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	7.0% 9/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders HYPOESTHESIA	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders SOMNOLENCE	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	6.2% 8/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	6.1% 2/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.8% 3/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders ALTERED STATE OF CONCIOUSNESS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Nervous system disorders POSTICTAL HEADACHE	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications CONTUSION	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	7.0% 9/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications EXCORIATION	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	9.1% 3/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications MOUTH INJURY	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Injury, poisoning and procedural complications PROCEDURAL COMPLICATION	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders AGITATION	2.5% 2/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.1% 4/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders AGGRESSION	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	2.3% 3/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders CONFUSIONAL STATE	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	3.0% 1/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders CRYING	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders LOGORRHEA	1.2% 1/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders DISORIENTATION	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders MOOD ALTERED	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.
Psychiatric disorders NERVOUSNESS	0.00% 0/81 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/128 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	0.00% 0/33 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.	1.3% 1/79 An adverse event is any untoward unfavorable unintended sign, symptom, or disease temporally associated with the use of drug, whether or not considered related to that drug. A serious adverse event is any untoward medical occurrence that results in death or disability/incapacity; is life-threatening; or requires or prolongs hospitalization.