A Study to Investigate the Efficacy, Safety and Tolerability of Four Different Doses of BI 409306 Compared to Placebo Given for 12 Weeks in Patients With Schizophrenia on Stable Antipsychotic Treatment.
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: BI 409306 100 mg QD; BI 498306 50 mg QD; Placebo; BI 498306 25 mg QD; BI 409306 10 mg QD
Intervention MeSH terms: BI 409306
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 518.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The objective of the study is to investigate the efficacy, safety and tolerability of four
      different doses of BI 409306 once daily compared to placebo given for 12 weeks in patients
      with schizophrenia on stable antipsychotic treatment.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with established diagnoses of schizophrenia (per Diagnostic and Statistical
             Manual of Mental Disorders, Fifth Edition (DSM-5)) with the following clinical
             features:

             a) Clinically stable and are in the residual (non-acute) phase of their illness for at
             least 8 weeks b) Current antipsychotic and concomitant psychotropic medications must
             meet the criteria below: b)-1 Maintained on current atypical (second generation)
             antipsychotic medications (in any approved dosage form) other than Clozapine and on
             current dose for at least 8 weeks prior to randomisation, and/or b)-2 Maintained on
             current typical (first generation) antipsychotic medications and on current dose for
             at least 6 months, optionally combined with anticholinergics if treated with a stable
             dose for at least 6 months prior to randomisation, and/or b)-3 Maintained on current
             concomitant psychotropic medications other than anticholinergics, antiepileptics and
             lithium, and on current dose for at least 8 weeks prior to randomisation.
             Antiepileptics and lithium are allowed if initiated at least 6 months prior to
             randomisation.

             b)-4 Anticholinergics, antiepileptics and lithium have been washed out for at least 6
             months prior to randomisation if the treatments that patients were using before
             entering the clinical trial are discontinued.

             c) Have no more than a "moderate" severity rating on hallucinations and delusions
             (Positive and Negative Syndrome Scale (PANSS)-positive syndrome Hallucinatory Behavior
             item score < =4 and Delusions item score < = 4) d) Have no more than a "moderate"
             severity rating on positive formal thought disorder (PANSS-positive syndrome
             Conceptual Disorganization item score < = 4) e) Have a minimal level of extrapyramidal
             symptoms (Simpson-Angus Scale total score < 6) and depressive symptoms (PANSS-general
             psychopathology syndrome Depression item score < = 4)

          2. Male or female patients age 18 to 55 years

          3. Patients must exhibit reliability, physiologic capability, and an educational level
             sufficient to comply with all protocol procedures,in the investigator's opinion.

          4. Signed and dated written informed consent by date of Visit 1 in accordance with GCP
             and the local legislation. If the patient needs a legal representative, then this
             legal representative must give written informed consent as well.

          5. Patients must have an identified informant who will be consistent throughout the
             study. The informant must interact with the subject at least 2 times a week.

        Note: Informant ratings are needed for SCoRS global ratings at Randomisation Visit (Visit
        2) and (early) End of Treatment Visit. In person informant ratings on the study visits are
        preferred whenever possible. However, if the informant is not available for in person
        ratings, telephone interview is acceptable. The informant must be available for a telephone
        interview at Visit 2 and (e)EOT Visit.

        Exclusion criteria:

          1. Patient treated with more than two antipsychotic medications (including more than two
             dosage forms)

          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. In the judgment of the investigator, any clinically significant finding of the medical
             examination (including BP, PR and ECG) or laboratory value deviating from normal or
             any evidence of a clinically significant concomitant disease or any other clinical
             condition that would jeopardize a patient's safety while participating in the clinical
             trial

          6. History or diagnosis of symptomatic and unstable/uncontrolled gastrointestinal,
             hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hematological
             or hormonal disorders

          7. For female patients:

             Pre-menopausal women (last menstruation < =1 year prior to informed consent) who:

               -  are nursing or pregnant or

               -  are of child-bearing potential and are not practicing an acceptable method of
                  birth control, or do not plan to continue using this method throughout the trial
                  until 28 days after the last treatment administration, and do not agree to submit
                  to periodic pregnancy testing during participation in the trial. Acceptable
                  methods of birth control include tubal ligation, vasectomized partner,
                  transdermal patch, intra uterine devices/systems (IUDs/IUSs), combined
                  estrogen-progestin oral contraceptives as well as implantable or injectable
                  hormonal contraceptives. Complete sexual abstinence (if acceptable by local
                  health authorities) is allowed when this is in line with the preferred and usual
                  lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation,
                  symptom-thermal, post-ovulation methods) and withdrawal are not acceptable
                  methods of contraception. Double barrier methods are permissible (if acceptable
                  by local health authorities, note that this is not an acceptable method in EU
                  countries).

             For male patients:

             Men who are able to father a child, unwilling to be abstinent or use adequate
             contraception for the duration of study participation and for at least 28 days after
             treatment has ended.

          8. Known history of HIV infection

          9. Diseases of the central nervous system (including but not limited to any kind of
             seizures, stroke or any psychiatric disorders other than schizophrenia)

         10. Any subject who on the Mini-international neuropsychiatric Interview (M.I.N.I.) has a
             categorical diagnosis of another current major psychiatric disorder.

         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. Significant history of drug dependence or abuse (including alcohol, as defined in
             DSM-5-substance use disorder 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, PCP, amphetamine, heroin, or marijuana at screening

         14. Patient needs to take long-acting hypnotics and anxiolytics (i.e. Diazepam)

         15. Patients taking medications that are known to be strong or moderate CYP3A4 inhibitors

         16. Participation in another trial with an investigational drug or procedure within 30
             days or 6 half-lives (whichever is longer) or participation in another trial with any
             cognitive-enhancing therapy or procedure within 90 days prior to screening

         17. Previous participation in any BI 409306 study

         18. Not fluent in the language of the batteries/questionnaires which will be used in the
             country