Safety and Tolerability of BI 409306 in Patients With Schizophrenia

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 409306 Film-coated Tablets Given Orally q.d. for 14 Days in Patients With Schizophrenia (Randomized, Parallel-group, Double-blind, Placebo-controlled Study)

The primary objective of the current study is to investigate the safety and tolerability of BI 409306 in schizophrenic patients following oral administration of multiple low, medium, and high doses over 14 days.

A secondary objective is the exploration of the pharmacokinetics and pharmacodynamics of BI 409306 in schizophrenic patients.

Inclusion criteria:

1. Patients with established diagnoses of schizophrenia (per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) with the following clinical features:

   1. Clinically stable and are in the residual (non-acute) phase of their illness for at least 8 weeks.
   2. Maintained on current antipsychotic medications and current dose for at least 8 weeks.
   3. Have no more than a moderate severity rating on hallucinations and delusions (e.g. Brief Psychiatric Rating Scale (BPRS) Hallucinatory Behavior or Unusual Thought Content item score < or =4).
   4. Have no more than a moderate severity rating on positive formal thought disorder (e.g. BPRS Conceptual Disorganization item score < or =4).
   5. Have no more than a moderate severity rating on negative symptoms (Positive and Negative Syndrome Scale negative syndrome total score <15).
   6. Have a minimal level of extrapyramidal symptoms (e.g. Simpson-Angus Scale total score < 6) and depressive symptoms (e.g. Calgary Depression Scale total score < 10).

2. Male or female patients age > or = 18 and < or =55 years.

3. Patients must exhibit reliability and physiologic capability to comply with all protocol procedures.

4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation. If the patient needs a legal representative, then this legal representative must give written consent as well.

Exclusion criteria:

1. Patient treated with more than one antipsychotic or not stabilized on antipsychotic treatment, or having had electroconvulsive therapy within the last 30 days
2. Patient's cognitive impairment severity compromises the validity of the cognitive outcome measures, in the clinical judgment of the investigator.
3. Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).
4. 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).
5. Any finding of the medical examination (including BP, PR and ECG) or laboratory value deviating from normal and of clinical relevance in the judgment of the investigator.
6. Any evidence of a clinically relevant concomitant disease.
7. History or diagnosis of symptomatic and unstable/uncontrolled gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, haematological or hormonal disorders.
8. Female patients that are of child-bearing potential or currently breastfeeding.
9. Known history, or new diagnosis per screening labs, of HIV infection.
10. History of neurologic (e.g. stroke, seizure without a clear and resolved etiology, concussion accompanying loss of consciousness) or psychiatric condition that the investigator deems may interfere with interpretability of data
11. History of malignancy within the last 5 years, except for basal cell carcinoma.
12. Planned elective surgery requiring general anaesthesia, or hospitalisation for more than 1 day during the study period.
13. Any other clinical condition that, in the opinion of the investigator, would jeopardize a patient's safety while participating in this clinical trial.
14. Significant history of drug dependence or abuse (including alcohol, as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) or in the opinion of the investigator) within the last two years prior to informed consent, or a positive urine drug screen for cocaine, opioid, phencyclidine (PCP), amphetamine or marijuana at screening.
15. Participation in another trial with an investigational drug or procedure within 30 days prior to screening or previous participation in any BI 409306 study.