- Increased the sample size from approx. 300 patients screened/180 randomized to approx. 380 patients screened/ 228 randomized; increased the number of sites to 60. -Indicated that mild sedation was to only be used in exceptional circumstances and that involvement of experienced personnel in the conduction of routine procedures was strongly recommended - Indicated that the Investigator was solely responsible for final decisions concerning subject eligibility - Clarified language concerning sparse PK sampling, certain inclusion/ exclusion criteria, remote visits, patient discontinuation and withdrawal, and time period when medication prohibitions applied - Stipulated that prolactin results remained blinded to investigator and sponsor (but was monitored independently by the CRO) - Reduced the recallperiod for the Caregiver Strain Questionnaire consistent with the time frame of the study - Added COVID-19 vaccination history or occurrence to assessments - Added pregnancy test at Week 3 - Adjusted contraceptive language to make it appropriate for premenarchal subjects - Defined caregivers allowed to provide input for caregiver-facing scales, and indicated that caregivers were trained in accurate symptom reporting for the ABC, Repetitive Behavior Scale-Revised, and CGSQ scales - Indicated that vital signs were optional at remote visits - Made the Week 4 visit an in-clinic visit with study drug dispensation - Added lorazepam as rescue medication

- Indicated that height, weight, and BMI measurements were optional at remote visits - Indicated that it is the sponsor/Medical Monitor who decides whether a patient who had taken prohibited medication continues in the trial - Added informed consent of a non-parent/LAR caregiver to the inclusion criteria and clarified informed consent language - Indicated that every attempt will be made to recruit equal numbers of patients from both age groups - Clarified inclusion criterion #8 so that patients will be screenfailures instead of withdrawn from the study if their ABC-I score at baseline exceeds ≥20% improvement from tje screening value - Clarified language relating to prior antipsychotic treatment - Adjusted exclusion criterion #16 to include blood pressure limits appropriate for both age groups - Removed physical examination from unscheduled visits - Updated the list of prohibited medications

- Specified that AEs of syncope and somnolence are actively monitored at each visit and that pertinent information was to be collected also as part of medical history - Adjusted exclusion criteria for blood pressure such that they were age-specific - Added stratification by geographic region (US versus rest of world) - Specified extension of the open-label extension study from 26 weeks to 52 weeks - Indicated that height should be measured using a stadiometer - Increased the frequency of ESRS-A assessments (to be conducted at all clinic visits) - Specified that all known potential class side effects of antipsychotics will be actively monitored - Added to the protocol appendix criteria for potentially clinically important laboratory values, ECG values, and vital signs - Specified that for patients reporting symptoms of orthostatic hypotension, this should be specifically measured - Specified that HbA1c was to be measured at all visits

- Allowed inclusion of patients on stable doses of stimulants and non-stimulants targeting irritability into the study - Provided flexibility in the timing of screening assessments, use of local laboratories, remote assessments, and conduct of the Autism Diagnostic Interview-Revised - Allowed for the capsule swallowing test to be passed either at screening or baseline - Adjusted the number of patients screened in the light of the higher-than-expected screen failure rate experienced in the study - Standardised washout periods to 5 half-lives or 2 weeks, whichever is longer - Removed the exclusion criterion regarding premature ventricular contractions (PVCs) - Updated the list of CYP3A4 inhibitors and inducers as per the FDA website