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

A Phase II Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered BI 409306 During a 28-week Treatment Period as Adjunctive Therapy to Antipsychotic Treatment for the Prevention of Relapse in Patients With Schizophrenia.

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.

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.