The key secondary endpoint changed from CGI I to CGI S. The description of the PE assessments at the ET Before Week 8 visit corrected to be consistent with the PE assessments at the other visits. Blood and ketones were added to the U/A assessment and the U/A microanalysis was deleted.

A correction in the text was necessary to specify that subjects are instructed to take 2 tablets/day during the taper phase or 1 tablet/day during the transition phase.

Schedule of Activities was updated to clarify that LFTs, serum lipids, serum creatinine and BUN or urea are collected as part of the blood chemistry evaluations, at the Screening and Week 8 visits. Inclusion criterion #1 has been modified requiring subjects to be a minimum of 7 years of age at the screening visit. Exclusion criterion #22 has been clarified regarding first-degree relative with bipolar disorder. Clarification was added to allow additional labeling on the study drug packaging if this does not obscure the Pfizer label. Revised the prohibited timeframe for formal psychotherapy from 90 days to 30 days, and deleted investigational procedures from the prohibited list. Text revised to clarify subjects who must sign an informed consent form are those reaching the age of majority rather than reaching the age of 18 years. Addition of atomoxetine, methaqualone and the phenothiazine class to the UDS testing list.

Schedule of activities was updated as follows: study visit naming conventions; provided additional wording regarding study visits out of window; provided additional wording regarding subjects who do not taper; clarified the information collected in the comprehensive psychiatric evaluation, added risk assessment wording. Revised term “final on-therapy” to “Week 8” in Endpoints. Inclusion and exclusion criteria were updated, contraception requirements and definition of childbearing were clarified, history of hypertension and suicide behavior ad baseline were clarified, suicidal ideation exclusion and risk assessment wording was also clarified. Lenth of time for post-study contraception was updated; medication error section was added. Double-Blind Treatment section was revised to clarify the study visit treatment phases and changed the requirement that the first dose should be taken on-site to a recommendation. Permitted and prohibited concomitant treatments were modified; definition of screen fail was clarified. Requirement for PI review of baseline ECG was added. Study visit schedule for participants who did not taper was clarified. Hy's Law criteria clarified, causality assessment definition clarified (AEs), reporting of exposures in utero clarified.

“Legal guardian”, “legally acceptable guardian” and “legally acceptable representative” revised to “parent(s)/legal guardian(s)” throughout; “clinical trial” revised to “clinical study” throughout and “study medication” and “investigational product” revised to “study drug” throughout where appropriate. Clarified approved use of fluoxetine and timing of CGI-I endpoint; clarified requirements for roll-over to extension study; revised approximate number of participants to delete requirement to enroll approximately the same number of children and adolescents; deleted requirement for an approximate 40-60 gender ratio within each age group. Clarified contraception requirements (inclusion criteria) and allergy to study drugs, contraception requirements and familial exclusion (exclusion criteria). Clarified that the placebo swallow test will be conducted at the study site; clarified to permit as-needed use of over-the-counter sleeping preparations and temporary use of a sedative-hypnotic for insomnia. Clarified informed consent/assent must be obtained at screening visit and that screening tests, assessments and procedures do not need to be completed in a single screening visit; clarified that same rater should be used for the Tanner and pregnancy tests are for all female participants regardless of age, sexual activity or menstrual status, clarified lifestyle discussion and use of age-appropriate C-SSRS version. Clarified screen failure criteria, specified first dose of study drug to be taken on-site, added study drug compliance assessment to the Weeks 5 & 7 study visits; clarified the liver-injury definition, the hospitalization definition, and the exposure during pregnancy and occupational exposure definitions as well as definition of withdrawal for AE. Revised interim analysis to allow for planned interim analysis when at least 75% of total participants have completed or had the opportunity to complete the 8-week double-blind treatment phase.