Clinical Trial of BI 425809 Effect on Cognition and Functional Capacity in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: BI 425809 dose 1; BI 425809 dose 2; BI 425809 dose 3; BI 425809 dose 4; Placebo
Intervention MeSH terms: BI 425809
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 509.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      The objective of the study is to investigate the efficacy, safety and pharmacokinetics of
      four different doses of BI 425809 once daily compared to placebo given for 12 weeks in
      patients with schizophrenia on stable antipsychotic treatment.
    

Eligibility criteria:

        Inclusion criteria:

          -  Men or women who are 18-50 years (inclusive) of age at time of consent

          -  Established schizophrenia with the following clinical features:

               -  Outpatient, with no hospitalization for worsening of schizophrenia within 3
                  months prior to randomisation

               -  Medically stable over the prior 4 weeks and psychiatrically stable without
                  symptom exacerbation within 3 months prior to randomisation

               -  patients who have no more than a moderate severe rating on the Positive and
                  Negative Symptom Scale (PANSS) positive items P1, P3-P7 and no more than a
                  moderate rating on the PANSS positive item P2

          -  Current antipsychotic and concomitant psychotropic medications as assessed at Visit 1
             must meet the criteria below:

               -  patients may have up to 2 antipsychotics (typical and/or atypical)

               -  patients must be maintained on current typical and/or atypical antipsychotics
                  other than Clozapine and on current dose for at least 4 weeks prior to
                  randomisation and/or maintained on current long acting injectable antipsychotics
                  and current dose for at least 3 months prior to randomization

               -  patients must be maintained on current concomitant psychotropic medications,
                  anticholinergics, antiepileptics and/or lithium for at least 3 months prior to
                  randomisation and on current dose for at least 4 weeks prior to randomisation

          -  Women of child-bearing potential must be ready and able to use highly effective
             methods of birth control that result in a low failure rate of less than 1% per year
             when used consistently and correctly.

          -  Patients must exhibit reliability, physiologic capability, and an educational level
             sufficient to comply with all protocol procedures, in the investigator´s opinion

          -  Patients must have an identified informant who will be consistent throughout the
             study.

          -  Further inclusion criteria apply

        Exclusion criteria:

          -  Patients who have a categorical diagnosis of another current major psychiatric
             disorder

          -  Diseases of the central nervous system that may impact cognitive test performance

          -  Movement disorder not currently controlled

          -  Patients receiving another investigational drug or procedure within 30 days or 6
             half-lives (whichever is longer) or recent participation in another trial with any
             cognitive enhancing therapy

          -  Recent participation in formal cognitive remediation program

          -  Recent electroconvulsive therapy

          -  Patients who have been on BI 409306, encenicline or other investigational drug testing
             effects on cognition in schizophrenia within the last 6 months prior to randomisation
             or who have previously been on bitopertin

          -  Participation in a clinical trial with repeated Measurement and Treatment Research to
             Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB)
             assessments within the last 6 months

          -  Patients who required change in ongoing stable benzodiazepine or sleep medication
             regimen within the last 4 weeks prior to randomisation

          -  Treatment with Clozapine within 6 months prior to randomisation

          -  Treatment with medical devices (e.g. Transcranial Magnetic Stimulation (TMS),
             neurofeedback) for any psychiatric condition within the last 3 months prior to
             randomisation

          -  Patients taking strong or moderate Cytochrome P450 (CYPA4) inhibitors or inducers
             within the last 30 days prior to randomization

          -  Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt,
             aborted attempt, or preparatory acts or behavior) prior to randomisation

          -  Any suicidal ideation of type 4 or 5 in the Columbia Suicidal Severity Rating Scale
             (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without
             specific plan, or active suicidal thought with plan and intent) prior to randomisation

          -  Known history of Human Immunodeficiency Virus (HIV) infection and/or a positive result
             for ongoing Hepatitis B or C infection on the Visit 1 central lab report

          -  Hemoglobin less than 120 g/L (12g/dL) in men or 115 g/L (11.5 g/dL) in women

          -  History of hemoglobinopathy such as thalassemia major or sickle-cell anemia

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial or
             men who are able to father a child, unwilling to be abstinent or use adequate
             contraception for the duration of the study participation and for at least 28 days
             after treatment has ended

          -  Significant history of drug abuse disorder (including alcohol) within the last 6
             months prior to informed consent or a positive urine drug screen at screening (except
             for Benzodiazepines taken according to prescription and as an ongoing, stable regimen)

          -  Further exclusion criteria apply