Amendment 1: • To clarify the definition of recurrence of seizures; • To clarify efficacy versus safety objectives and to modify secondary and exploratory objectives; • To provide observation periods for the time to next seizure after study drug administration; • To clarify instructions for administering the second dose of study drug; • To clarify that medical history was to be taken at Visit 1 only; • To update the safety objectives and assessments to streamline the list of safety assessments; • To clarify inclusion and exclusion criteria; • To add test for phenobarbital in participants; • To clarify that the caregiver is to record the actual time of return to baseline activity; • To clarify requirement for training of the caregiver; • To remove the requirement to have a legally acceptable representative (LAR) co-sign the assent document with the participant; • Participant and caregiver satisfaction questionnaire, quality of life (QOL), and other health economic assessments at Visit 2 was moved from post-dose to before the administration of the first test dose; • To change the maximum amount of blood to be collected for PK analyses from 275 mL to 50 mL; • To update the permitted and prohibited medications and substances; • To include more information on the use of flumazenil in treating MDZ overdose per prescribing information of MDZ injection; • To clarify that adverse events (AEs) and serious adverse events (SAEs) were to be collected until 30 days after completing of the final study Visit; • To clarify statistical methodology; • To adjust time window for the occurrence of Visit 4 from 48 to 120 hours after study drug administration to 24 to 120 hours after study drug administration; • To add windows for completion of assessments at Visit 2 and change measurement of temperature to pre-dose only; • To allow extension of the Screening period; • To clarify instructions for repeating out-of-range vital signs.

Amendment 2: • To modify the trial to utilize a group sequential design with 3 interim analyses and a maximum of approximately 240 participants who have completed the CP; • To remove the requirement for emergency rescue treatment with assisted breathing or intubation within 24 hours after study drug administration; • To decrease the lower age (from 14 to 12 years of age) and remove the upper age restriction from Inclusion Criterion 3; • To modify the definition of intermittent use of benzodiazepines to clarify that benzodiazepines are allowed provided they are typically used ≤ 3 days within a 7-day period; • To reduce the minimum observation time at the Test Dose Visit from 4 hours to 1 hour for all new test dosed participants after the originally planned 132 participants completed the CP; • To modify Exclusion Criterion 22 to clarify that a that a ≥ 40 mmHg decrease from baseline in systolic blood pressure (SBP) and a ≥ 30 mmHg decrease from baseline in diastolic blood pressure (DBP) during the observation period after administration of the USL261 test dose at Visit 2 were exclusionary; • To remove date and time of recognition of seizure cluster(s) eligible for treatment with study drug from the list of efficacy assessments; • To reduce the AE reporting time frame from 30 days after the last administration of study drug to 7 days after the last administration of study drug; • To clarify that participants who did not have sufficient available data to confirm whether they could be classified either as “Treatment Success” or as “Not a Treatment Success” were considered to have missing data; • To clarify that the PK profile after administration of any dose of USL261 would be evaluated, not just after 10 mg; • To update the statistical and PK analyses to provide additional detail on the planned analyses; • To clarify that participants who had not treated a seizure cluster meeting the study criteria within 6 months of randomization were to be discontinued from the study.

Amendment 3: • To update the definition of modified Intent-to-Treat (mITT) to maintain the wording in the original protocol (include only those participants who received at least 1 dose of study drug during the CP and who had any post-treatment efficacy assessments); • To update the statistical analysis of the primary efficacy endpoint to maintain the analyses in the original protocol and add chi-squared test as a sensitivity analysis.

Amendment 4: • To add the Brief Smell Identification Test (B-SIT) at US sites to assess the effects of USL261 on olfaction; • To update the procedures to be completed at Visits 1, 4, and on the monthly telephone follow-up calls between Visit 3 and Visit 4; • To update the introduction section to reflect current study status; • To clarify that the time between Visit 2 and Visit 3 may be extended, and that the extension must be approved by the Sponsor or Clinical Research Organization designee.