This Study Tests Whether BI 409306 Prevents Patients With Schizophrenia From Becoming Worse. This Study Looks at How Well Patients Tolerate BI 409306 and How Effective it is Over 6 Months
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: BI 409306; Placebo
Intervention description: 28 week treatment period; 28 week treatment period
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: 264.0
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 BI
      409306 once daily compared with placebo given for 28 weeks in patients with schizophrenia on
      antipsychotic treatment. The study is designed to show superiority of BI 409306 over placebo
      in preventing relapse of schizophrenia symptoms.
    

Eligibility criteria:

        Inclusion Criteria:

          -  International Statistical Classification of Diseases and Related Health Problems, 10th
             Revision (ICD-10) diagnosis of schizophrenia >= one year prior to randomisation.

          -  Outpatients in the stable phase of illness, as assessed by the investigator after
             review of medical records or documented discussion with treating clinician.

          -  Patients currently taking a stable dose of antipsychotic medication(s) for at least 12
             weeks prior to randomisation.

          -  Detectable level of current antipsychotic medication(s) in plasma from blood drawn at
             Visit 1 (unless no assay is available for the antipsychotic(s) currently prescribed).

          -  Patients who have experienced at least 2 relapses within the past 5 years or at least
             1 relapse if they were diagnosed less than 3 years ago. Relapse is defined as the
             patient having any of the following using the above number of relapses and time
             frames:

               -  Hospitalization for psychosis (involuntary or voluntary admission), intensive
                  outpatient therapy or use of home treatment as an alternative to hospitalization
                  (verified via medical record).

               -  Emergency Department visit for worsening schizophrenia symptoms (verified via
                  medical record).

               -  Deliberate self-injury and/or violent behaviour resulting in significant injury
                  to another person or property (verified by police record or treating mental
                  health provider written record or documented phone conversation).

               -  Change in the patient's antipsychotic medication or increase in antipsychotic
                  medication dosage due to worsening of schizophrenia symptoms (verified by
                  pharmacy records or treating mental health provider written record or documented
                  phone conversation).

          -  Clinical Global Impressions-Severity (CGI-S) score ≤4 at Visit 1 and 2.

          -  Positive and Negative Syndrome Scale (PANSS) total score <80 and a score of ≤ 4 on
             individual PANSS items conceptual disorganization, hallucinatory behavior,
             suspiciousness, and unusual thought content at Visit 1.

          -  Of full age (according to local legislation, usually ≥ 18 years) and ≤ 55 years at the
             time of informed consent.

          -  Patients must have an identified informant who will be consistent throughout the
             study.

          -  Patients who report living at the same address for the 3 months prior to
             randomisation.

          -  Male or female patients.

             -- Female patients of childbearing potential must be ready and able to use highly
             effective methods of birth control per International Conference on Harmonisation (ICH)
             M3 (R2) that result in a low failure rate of less than 1% per year when used
             consistently and correctly. Patients must agree to use birth control throughout the
             trial and for at least 28 days after treatment has ended. Acceptable methods of birth
             control include combined estrogen-progestin oral, intravaginal or transdermal
             contraceptives, progestogen-only oral, injectable or implantable contraceptives,
             intrauterine devices (IUDs), intrauterine hormone releasing systems (IUSs), bilateral
             tubal occlusion, vasectomized sexual partner, and complete sexual abstinence (if
             acceptable by local health authorities) is allowed when this is in line with the
             preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar,
             ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable
             methods of contraception.

          -  Male patients who are able to father a child must be ready and able to be abstinent or
             use adequate contraception for the duration of study participation and for at least 28
             days after treatment has ended.

          -  Signed and dated written informed consent in accordance with International Conference
             on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to
             admission to the trial. If the patient has a legal representative, then this legal
             representative must give written informed consent as well.

        Exclusion criteria:

          -  Patients treated with more than two antipsychotic medications (including more than two
             dosage forms).

          -  Patients who are currently being treated with clozapine, or who have been treated with
             clozapine in the past 5 years.

          -  Patients with a categorical diagnosis of another current major psychiatric disorder
             per the Mini-international neuropsychiatric Interview (M.I.N.I.).

          -  Homicidal behaviour (in the investigator's judgement) in the past 2 years.

          -  Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt,
             aborted attempt, or preparatory acts or behavior).

          -  Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale
             (CSSRS) in the past 3 months (i.e. active suicidal thought with intent but without
             specific plan, or active suicidal thought with plan and intent).

          -  In the judgment of the investigator, any clinically significant finding from the
             physical examination 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.

          -  Other known neurological diseases (including but not limited to any kind of seizures
             or stroke).

          -  Any documented active or suspected malignancy or history of malignancy within 5 years
             prior to screening, except appropriately treated basal cell carcinoma of the skin or
             in situ carcinoma of uterine cervix.

          -  Planned elective surgery requiring general anesthesia, or hospitalization for more
             than 1 day during the study period.

          -  Significant history of drug or alcohol dependence or abuse (Substance Use Disorder as
             defined in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
             or ICD-10) within the last six months prior to informed consent. (Not including
             caffeine or nicotine).

          -  Patients who must or wish to continue the intake of restricted medications or any drug
             considered likely to interfere with the safe conduct of the trial.

          -  Patients taking strong or moderate CYP1A2 inhibitors who are also a CYP2C19 Poor
             Metabolizer (PM). Patients taking medication known to be strong or moderate inhibitors
             of CYP1A2 must be prospectively genotyped to ensure they are not poor metabolizers of
             CYP2C19. (A list of CYP1A2 and CYP2C19 inhibitors can be found in the Investigator
             Site File (ISF)).

          -  Patients taking strong or moderate CYP1A2 inhibitors who are also taking concomitant
             strong or moderate CYP2C19 inhibitors. (A list of CYP1A2 and CYP2C19 inhibitors can be
             found in the ISF)

          -  Patients with a history of moderate to severe hepatic impairment (Child-Pugh B / C).

          -  Patients with a history of moderate to severe renal impairment (Stage 3 - 5).

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial.

          -  In the judgment of the investigator, inability of the patient to comply with the
             clinical trial procedures.

          -  Currently enrolled in another investigational device or drug study, or less than 6
             months from Visit 1 since ending another investigational device or drug study(s), or
             participation in > 2 investigational drug clinical trials in the past 2 years.

          -  Previous randomisation in any BI 409306 study.