The key secondary endpoint was changed from CGI-I to CGI-S. The physical examination assessment performed at the early termination before Week 8 visit was revised for consistency with those performed at other visits. Blood and ketones were added to the urinalysis laboratory assessment and urinalysis microanalysis was deleted.

Updated stratification factors to indicate that participants would be stratified by both age and country. Exclusion criterion 27 for the screening visit was corrected to reflect that participants who were dependents of investigational site staff members to participants who were dependents of Pfizer employees directly involved in the conduct of the study were not eligible for the study. The tests/procedures/assessments listed for the unscheduled visit were corrected to reflect that vital sign measurements included collection of temperature and respiratory rate and to reflect that concomitant treatment information was collected. Additional details were added to describe the planned interim analysis.

The schedule of activities was updated to reflect clearly that blood chemistry laboratory assessments completed at screening and Week 8 visits included liver function tests, serum lipids, serum creatinine, and blood urea nitrogen or urea. Inclusion criterion 1 was modified to require participants to be a minimum of 7 years of age at the screening visit. Exclusion criterion 22 for the screening visit was clarified regarding first degree relative with bipolar disorder. Text was clarified to reflect that no repackaging or labelling of study drug containers was done at the site that would obscure the Pfizer label. Text was revised to reflect that participants who reached the age of majority, as recognised by local law, during study participation signed the informed consent document. Text specific to urine drug screen information was updated. Text was corrected to clarify that the efficacy assessments (CDRS-R, CGI-S, and CGI-I) were not completed at the Week 9 visit. Repetitive information describing the interim analysis was removed.

Revised Inclusion & Exclusion Criteria at Screening & Exclusion Criteria at baseline. Additional instruction regarding contraception requirements, increased post-study contraception requirements & changed “medically approved contraception” to “highly effective contraception” for male & female sexually active participants. Removed text relating to clinical studies in adults with MDD & deleted historical numbers of adult studies. Separated secondary objectives into key & other; clarified other objectives. Revised term “final on-therapy” to “Week 8”. Revised text to add storage requirements. Clarified collection requirements for prior psychiatric treatments & added examples of permitted concomitant treatments. Added linezolid, methylene blue & selegiline to monoamine oxidase inhibitor category in prohibited concomitant medications. Added provision for consideration of occasional use of prohibited treatments. Clarified assignment of participant numbers via Impala & clarified sections of K-SADS-PL to be completed. Clarified definition of screen failure. Added requirement for investigator review of baseline echocardiogram; revised a requirement to a recommendation that the first dose should be taken on-site. Clarified study visit schedule for participants who do not taper, & that the taper phase may not have been extended. Clarified several study assessments: general corrections to study visit names, collection timeframes & added rater requirement reference; vital signs, pregnancy test, laboratory, pharmacokinetic sampling (fasting requirements), psychiatric evaluation, various scales, K-SADS-PL, Columbia-Suicide Severity Rating Scale (C-SSRS), & risk assessment was added. Clarified AE/SAE classification, reporting period, causality assessment, Hy’s Law criteria, exposure in utero, & overdose: specified the case report forms to be completed. Clarified the timing/population of the interim analysis, the IDMC study responsibilities & the Pfizer record retention policy.

Grammatical revisions & typographical error corrections: “legal guardian”, “legally acceptable guardian” &“legally acceptable representative” revised to “parent(s)/legal guardian(s)”throughout; “clinical trial” revised to “clinical study” throughout & “study medication” & “investigational product” revised to “study drug” throughout where appropriate. Added specific studies “(B2061030 & B2061031)” to follow “extension study” for clarification. Clarified timing of CGI-I endpoint. Clarified requirements for roll-over to extension study. Deleted requirement to enrol approximately the same number of children & adolescents & deleted requirement for an approximate 40-60 gender ratio within each age group. Clarified contraception requirements; clarified the following exclusion criteria: allergy to study drugs, contraception requirements & familial exclusions. Clarified drug storage requirements. Clarified the Medication Error case report form page to be a type of AE case report form page. Specified the placebo swallow test was conducted at the study site. Permitted as-needed use of over-the-counter sleeping preparations & temporary use of a sedative-hypnotic for insomnia. Clarified that informed consent/assent was obtained at the screening visit; clarified that screening tests, assessments & procedures did not need to be completed in a single visit; clarified that where possible the same rater was used for the Tanner, clarified pregnancy tests were for all female participants regardless of age, sexual activity or menstrual status, clarified lifestyle discussion & clarified use of age-appropriate C-SSRS version. Clarified screen failure criteria. Clarified definitions for liver injury, hospitalisation, exposure during pregnancy, occupational exposure definition, and withdrawal for AE. Revised planned interim analysis for when at least 75% of total participants had completed or had the opportunity to complete the 8-week double-blind treatment phase.