- 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
- 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
- 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
- Clinical Global Impressions-Severity (CGI-S) score â‰¤4 at Visit 1 and 2.
- Positive and Negative Syndrome Scale (PANSS) total score <80 and a score of â‰¤ 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 â‰¥ 18 years) and â‰¤ 55 years at the
time of informed consent.
- Patients must have an identified informant who will be consistent throughout the
- Patients who report living at the same address for the 3 months prior to
- 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.
- Patients treated with more than two antipsychotic medications (including more than two
- 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
- 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.