This Study Tests Whether BI 425809 Together With Brain Training Using a Computer Improves Mental Functioning in Patients With Schizophrenia

MCCB neurocognitive composite T-score assesses 6 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving. MCCB neurocognitive T-scores in the general population have a mean of 50 and standard deviation of 10. A higher T-score indicates better cognition. Change from baseline in MCCB neurocognitive composite T-score at Week 12 was modelled based on a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (screening, baseline, week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group, and continuous covariate of change from screening to baseline value. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.

Time frame: At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.

Population: Full Analysis Set (FAS) includes all patients in treated set (TS) who had non-missing baseline and at least 1 non-missing post-baseline on-treatment measurement of the primary efficacy endpoint. The FAS was used for efficacy analyses. Patients were analysed as randomised.

MCCB cognitive score comprises 10 tests, which assess 7 cognitive domains, including speed of processing, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. MCCB cognitive T-scores in the general population have a mean of 50 and standard deviation of 10. A higher T-score indicates better cognition. Change from baseline in MCCB overall composite T-score was modelled using a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (screening, baseline, week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group, and continuous covariate of change from screening to baseline value. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.

Time frame: At screening (28 days prior to first drug drug administration), at baseline and at Weeks 6 and 12 after first drug administration.

Population: Full Analysis Set (FAS) includes all patients in treated set (TS) who had non-missing baseline and at least 1 non-missing post-baseline on-treatment measurement of the primary efficacy endpoint. The FAS was used for efficacy analyses. Patients were analysed as randomised.

PANSS was used to evaluate broad psychopathology associated with schizophrenia disease state. The PANSS has 30 items. Each is rated from 1 to 7 points. The total factor score is the summation of the actual points for each item, leading the total score ranging from 30 to 210; a higher score indicates a worse disease condition. Change from baseline in PANNS total score after 12 weeks of treatment was modelled based on a restricted maximum likelihood (REML) based approach using a mixed model with repeated measurements (MMRM) which included the following fixed effects: categorical factor of planned treatment, visit (baseline, Week 6 and Week 12), planned treatment by visit interaction, continuous covariate of baseline value, baseline by visit interaction, categorical factor of age group. The Least Squares Mean (95 % Confidence Interval) at Week 12 is reported.

Time frame: At baseline and at Weeks 6 and 12 after first drug administration.

Population: Full Analysis Set (FAS) includes all patients in treated set (TS) who had non-missing baseline and at least 1 non-missing post-baseline on-treatment measurement of the primary efficacy endpoint. The FAS was used for efficacy analyses. Patients were analysed as randomised. One patient in the arm Placebo + Computerized Cognitive Training was excluded from the statistical model, because the patient did not have post-baseline PANSS total score values.

Schizophrenia Cognition Rating Scale (SCoRS) is a 20-item interview-based assessment of cognitive deficits and the degree to which they affect day-to-day functioning. Each item is rated on a 4-point scale. SCoRS total score is between 20 and 80 where higher score values represent greater degree of impairment in day-to-day functions due to cognitive deficits. The composite score was the average of non-missing responses. If five or more of the 20 items were missing, the composite score was missing for that participant at the visit. Change from baseline in SCoRS total score after 12 weeks of treatment was modelled using an Analysis of Covariance (ANCOVA) which included the following fixed effects: categorical factor of planned treatment, continuous covariate of baseline value, categorical factor of age group.

Time frame: At baseline and at 12 weeks after first drug administration.

Population: Full Analysis Set (FAS) includes all patients in treated set (TS) who had non-missing baseline and at least 1 non-missing post-baseline on-treatment measurement of the primary efficacy endpoint. The FAS was used for efficacy analyses. Patients were analysed as randomised. Only patients with non-missing results at Week 12 are reported.

Percentage of patients with any Adverse Event (AE) and with serious adverse events (SAEs) is reported. Percentages were rounded to one decimal place.

Time frame: From first dose of study drug administration until four weeks after the last dose of study drug administration, up to 16 weeks.

Population: Treated Set (TS) includes all patients in randomized set (RS) who were treated with at least 1 dose of the trial regimen (including both trial drug and computerized cognitive training (CCT)).