Table 1.

Study endpoints

Primary endpoint

Change from baseline in neurocognitive function as measured by the neurocognitive composite score of the MCCB after 12 weeks of treatment

The neurocognitive score includes all MCCB domains except social cognition

Secondary efficacy endpoints

Change from baseline in cognitive function as measured by the overall MCCB score after 12 weeks of treatment

The overall score includes all MCCB domains

Change from baseline in the effect of cognitive deficits on day-to-day functioning as measured by the SCoRS after 12 weeks of treatment

SCoRS is a 20-item interview-based assessment of how cognitive deficits affect day-to-day functioning

Change from baseline in PANSS total score after 12 weeks of treatment

PANSS will be used to evaluate broad psychopathology associated with schizophrenia disease state

Further efficacy endpoints

Change from baseline in each of the 7 MCCB domain scores after 12 weeks of treatment

Change from baseline in PANSS Positive Symptom Scale after 12 weeks of treatment

Change from baseline in PANSS Negative Symptom Scale after 12 weeks of treatment

Change from baseline in PANSS Emotional Expression and Emotional Experience Subscales after 12 weeks of treatment

Change from baseline in CGI-S score after 12 weeks of treatment

CGI-S is a one-item evaluation completed by the clinician to measure the severity of the patient’s psychopathology

Change from baseline in BET scores after 12 weeks of treatment

The BET is a computerized task that assesses the patient’s willingness to exert effort for reward

PRECIS score (in English-speaking patients only)

PRECIS is a novel patient-reported instrument developed to record patients’ subjective experience of CIAS, and the results of this study will support the validation of this outcome measure

Change from baseline in VRFCAT time to completion, number of errors, and forced progressions after 12 weeks of treatment

The VFRCAT is a computerized virtual reality shopping trip developed to detect functionally meaningful improvements in patients’ everyday lives, and outcomes will help to evaluate whether an augmentation approach translates to improved functional performance

CCT performance after 12 weeks will be measured using a global progression scale, which is an average of the level of progression across each exercise

Safety endpoints

Percentage of patients with AEs and SAEs

Including clinically relevant abnormalities identified in physical examination, vital signs, ECG, and laboratory tests

Occurrence of protocol specified AESI

Worsening of disease state as assessed by PANSS

Suicidality as assessed by C-SSRS

Pharmacokinetic endpoints

Pre-dose/trough plasma concentrations of BI 425809 at Visits 3, 4, 5, and 6

To measure study drug compliance

AEs adverse events, AESI adverse event of special interest, BET Balloon Effort Task, CCT computerized cognitive training, CGI-S Clinical Global Impressions-Severity, CIAS cognitive impairments associated with schizophrenia, C-SSRS Columbia Suicide Severity Rating Scale, ECG electrocardiogram, MCCB Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery, PANSS Positive and Negative Syndrome Scale, PRECIS Patient Reported Experience of Cognitive Impairment in Schizophrenia, SAEs severe adverse events, SCoRS Schizophrenia Cognition Rating Scale, VRFCAT Virtual Reality Functional Capacity Assessment Tool