The study protocol was amended to clarify that medication adherence and reminder system is not mandatory. To clarify special situations where hospital visits would be considered serious adverse events (SAEs), and update list of Cytochrome P450 (CYP) 3A4 inhibitors and inducers.

The study protocol was amended to incorporate site feedback regarding rater review for the MINI, to include that audio recording would be conducted during the MINI at the Screening Visit in order to ensure rater accuracy via central calibration/reading. Additionally, to specify that, in the US, previous antipsychotic exposure is required for paediatric subjects (greater than or equal to 16 years and less than 18 years of age) to qualify for participation in the study. To specify that clinically significant ECG abnormalities are exclusionary at Visit 1 only. To update the criteria for defining a serious adverse event (SAE).

The study protocol was amended to allow for the addition of a new exclusion criterion for subjects with known risk of narrow-angle glaucoma to align with olanzapine (OLZ) local labels, including the current Summary of Product Characteristics (SmPC). Additionally, to revise serum creatinine exclusion criterion, to revise inclusion criterion for antipsychotic treatment eligibility requirement, to revise exclusion criterion for suspected intolerance, allergy, or hypersensitivity to study drug to include any of the ingredients of the study drug. Further describe medications that exhibit drug interaction potential with OLZ, including detail on inhibitors and inducers of CYP 1A2 and of medicinal products known to increase QTc interval.

The study protocol was amended to update the inclusion and exclusion criteria, to add instructions for stoppage of treatment with mood stabilizers, to clarify use of a study-approved and calibrated scale for body composition analyzer measurements, to update the language regarding contraception requirements and to add additional randomization stratification factor.

The study protocol was amended to increase the sample size from 250 to 400 subjects in the efficacy population and remove the interim analysis. Approximately 425 subjects were proposed to be randomized to have 400 subjects in the efficacy population. To add additional secondary endpoints as follows: Change from baseline in waist circumference at Week 12, and change from baseline in CGI-S score within the ALKS 3831 Group at Week 12. Additionally, to make changes to other endpoints, revise methods for handling missing data and when multiple imputation (MI), summary statistics, or mixed model with repeated measurements (MMRM0 was performed. Changes were made to collection of data for randomized subjects who terminated the treatment early. Clarifications were made regarding subject eligibility (inclusion and exclusion criteria). The addition of Olanzapine (OLZ) starting dose 20 mg and ALKS 3831 starting dose of 20/10 mg during the first week of treatment. To clarify the requirements for selective serotonin reuptake inhibitor (SSRI) antidepressant use for subjects with schizophrenia and schizophreniform disorder. Addition of laboratory blood tests.