Part 1: A number of additions to trial procedures intended to enhance participant safety and accuracy of data were made: Replaced Brief Assessment of Cognition in Schizophrenia with Trails A, Tower of London, and Letter-Number Span cognition assessments; revised post-treatment follow-up to include phone calls 20 and 26 weeks after the last visit; added assessment of haemoglobin A1c if fasting glucose was ≥125 milligrams/decilitre (mg/dL) and/or the urinalysis was positive for glucose; included varenicline as a prohibited concomitant medication; added assessment of electrocardiogram (ECG) at the end of the Conversion Phase for participants who terminated prematurely from the Conversion Phase; added individual durations of pregnancy monitoring based on formulation of aripiprazole; added details for the determination of starting dose in the Oral Stabilization Phase based on the participant’s prior history with the double-blind trials and oral aripiprazole; added descriptions for determination of body mass index and waist circumference; added requirement for withdrawal of participants who continued to meet exacerbation of psychotic symptoms/impending relapse criteria after receiving 3 episodes of oral aripiprazole tablet rescue therapy. Participants not meeting stability criteria, but not in impending relapse could continue in the trial at the investigator’s discretion; added requirement that participants meeting exacerbation of psychotic symptoms/impending relapse criteria must receive oral aripiprazole tablet rescue therapy.

Part 2: Revised exclusion criterion related to abstinence/contraceptive use based on half-life of aripiprazole; clarified that participants who receiving aripiprazole in combination with any other antipsychotic(s) must enter the Conversion Phase in order to discontinue other antipsychotic(s). Only participants who received aripiprazole as monotherapy after the last visit of Trials 246/247 or at screening of Trial 31-08-248 (if applicable) could progress directly to the Oral Stabilization Phase; revised key secondary efficacy endpoints based on feedback from the Food and Drug Administration and adjusted statistical methods accordingly; clarified rules for rescue therapy; replaced Columbia Suicide Severity Rating Scale(C-SSRS) in protocol appendix; specified that a modified version of the CSSRS-European Version would be used for this trial to reduce redundant data capture and replace the sample form in the appendix with the modified form; removed table of trial day intervals for determination of visit dates; clarified that the last visit of the Open-label IM Depot Maintenance Phase was required to occur 379 days (1 year plus 2 weeks) after the first dose of open-label aripiprazole IM depot; clarified that Investigator Assessment and Patient Satisfaction with Medication Questionnaire -Modified should be completed only for participants who participated in the Conversion Phase of Trial 248 or de novo participants who had not been enrolled in Trials 246/247 so that treatment with aripiprazole IM depot could be compared with other antipsychotic(s) taken prior to entry into Trial 31-08-248; clarified that participants receiving more than one benzodiazepine at screening could qualify for the trial if they discontinued one of the benzodiazepines during the screening period; clarified that investigator- and subject-rated assessments of injection site were to be based on the site of the most recent injection; ECGs would be obtained “approximately” 5 minutes apart.

Part 1: Updated general information on aripiprazole in introductory sections based on most recent Investigator Brochure and completed clinical study reports; revised trial design description to clarify antipsychotic medication requirements at screening (including definition of “lapse” in aripiprazole or antipsychotic medication at time of trial entry), as these requirements related to participant entry into the Conversion Phase vs directly into the Oral Stabilization Phase of the trial; clarified language regarding “non-generic oral aripiprazole monotherapy (trial drug).”; added a table delineating recommendation for switching from other generic oral aripiprazole to non-generic oral aripiprazole monotherapy; changed nomenclature of “additional” participants to “new” participants (participants who had not been enrolled in either Trial 31-07-246 or Trial 31-07-247 who enroll in Trial 31-08-248 as their first aripiprazole IM depot trial); Clarified Personal and Social Performance Scale as “other” assessments rather than “efficacy” assessments; added that a pharmacokinetic blood sample was to be collected in the event of a serious adverse event in the Open-label IM Depot Maintenance Phase (aripiprazole IM depot phase only); clarified that the aripiprazole IM depot injection site would be evaluated before and after each injection. Immediately prior to the first aripiprazole IM depot injection site, the anticipated injection site was to be evaluated; added assessment of C-SSRS at all postbaseline visits, rather than as determined by CGI-SS score, and renaming the “postbaseline C-SSRS” as “C-SSRS since last visit.”; refined exclusion criteria regarding screening ECG values for QTc interval; Clarified information that should be included in source documentation; clarified that prolactin levels would be assessed at Week 6/end of the Conversion Phase/ET; clarified that participants who discontinued any phase of the trial were not eligible to be rescreened to enter the trial

Part 2: Included explanation that the Letter-Number Span assessment of cognition was not able to be completed in countries with Cyrillic and character-based languages; included a requirement for the physical examination to include the genitourinary body system with the option that the assessment could be performed within 1 year prior to the end of the screening period provided that documentation of the examination and records of results were provided to the trial investigator. A genitourinary examination was required annually (every 52 weeks) during the trial; clarified allowances/restrictions regarding concomitant medications (zolpidem extended-release, propranolol); added instruction to investigators regarding subject false-positive drug screen results during the trial; revised statistical analysis methods; replaced PANSS and C-SSRS in protocol appendix with most current versions; revised Resource Utilization Questionnaire; added Subject Experience with IM Depot Medication survey; clarified initiation of rescue therapy strategy; updated trial design to include the long-term extension trial; clarified the stability assessment to be done at Weeks 3, 6, and 10; increased the number of participants from 500 to 500-800. In addition, a number of administrative clarifications were made, including changes to text to enhance readability and correct typographical errors.