The following changes were implemented with Amendment 1: • Used the clinician-rated Columbia–Suicide Severity Rating Scale (C-SSRS), rather than the patient-rated scale, in order to provide greater clinical oversight • Clarification of the following exclusion criteria: - 6: was modified to reflect the classification of substance-related disorders - 16: was modified to clarify the allowed duration and to ensure consistency of bipolar disorder diagnosis - 18: was revised to clarify and limit the doses and allowances for benzodiazepines • Deletion of exclusion criterion 19: because cariprazine had been approved for prescription use (in the United States), there was no clinical rationale for excluding participants with prior participation in a cariprazine study. • Addition of an exclusion criterion (23) addressing use of contraception for male participants; and amendment of exclusion 24 to clarify allowable contraception methods Clarification of Table 9.4.5-1 (blister card configuration and dosing regimen); • Clarification on the use of lorazepam (or equivalent benzodiazepine) as rescue medication for agitation, restlessness, and hostility, and removal of the restriction on injectable benzodiazepine agents for use as rescue medication for agitation, restlessness, and hostility.

The following changes were implemented with Amendment 2: Revised the wording of exclusion criterion 18 to correct an error (ie, the omission of the word “no” in the sub-bullet pertaining to use of benzodiazepines, which caused this exception to exclusion criterion 18 to convey the reverse of what was intended).