Eligibility Details:
Inclusion Criteria:
- Signed and dated written informed consent in accordance with ICH Harmonized Tripartite
Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to
admission to the trial.
- Male or female patients who are 18-50 years (inclusive) of age at time of consent.
- Established schizophrenia (as per DSM-5) with the following clinical features:
- Outpatient, with no hospitalization for worsening of schizophrenia within 3
months prior to randomization
- Psychiatrically stable without symptom exacerbation within 3 months prior to
randomization
- PANSS score ≤ 5 on positive items P1, P3-P7 and ≤ 4 on positive item P2 at Visit
1, and confirmed at Visit 2
- Patients must be on stable antipsychotic treatment, and current antipsychotic and
concomitant psychotropic medications must meet the criteria below:
- Patients may take up to 2 antipsychotics (typical and/or atypical), except for
clozapine
- Patients must be stable on current antipsychotics and concomitant psychotropic
medications (e.g. anticholinergics, antiepileptics, lithium and allowed
antidepressants) for at least 3 months prior to randomization and be on current
dose for at least 30 days prior to randomization ---Patients on Long-Acting
Injectable (LAI) antipsychotics should be on the same medication and dose for at
least 3 months prior to randomization
- Women of childbearing potential (WOCBP)2 must be ready and able to use highly
effective methods of birth control per Non-Clinical Safety Studies for the Conduct of
Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3 (R2))
that result in a low failure rate of less than 1% per year when used consistently and
correctly. Such methods should be used throughout the trial, and for a period of at
least 35 days after last trial drug intake, and the patient must agree to periodic
pregnancy testing during participation in the trial.
- Patients must demonstrate their ability to properly use the computerized cognitive
training (CCT) device and program, as well as be compliant with CCT run-in (defined as
completing at least 2 hours per week for two weeks, totalling 4 hours CCT, during the
screening period).
- Patients must be able to comply with all protocol procedures including the at-home CCT
exercises, in the investigator's opinion.
- Patients must have a study partner who will preferably be consistent throughout the
study. It is recommended that the study partner should interact (in-person or
telephone) with the subject at least 2 times a week.
Exclusion Criteria:
- Patients who have a categorical diagnosis of another current major psychiatric
disorder on the Mini-International Neuropsychiatric Interview (M.I.N.I.).
- Diseases of the central nervous system (CNS) that may impact the assessment of the
cognitive tests as per investigator's opinion.
- A movement disorder due to antipsychotic treatment not currently controlled with anti-
EPS treatment or another movement disorder (e.g. Parkinson´s disease).
- Patients with a history of participating in any formal cognitive remediation program
for 10 or more training sessions.
- Patients who were treated with any of the following medications within the last 6
months prior to randomization:
- Bitopertin, BI 409306, encenicline or other investigational drug testing effects
on cognition in schizophrenia
- Clozapine (atypical antipsychotic medication)
- Sarcosine, cycloserine, serine and glycine
- Stimulants (e.g. methylphenidate, dextroamphetamine, modafinil)
- Tricyclic antidepressants
- Patients receiving any other investigational drug (other than a potential cognitive
enhancing drug) within 30 days or 6 half-lives (whichever is longer) prior to
randomization. For investigational LAI antipsychotics, the last injection must be at
least 3 months or two administration cycles (i.e. 6 months if administration is every
3 months) prior to randomization, whichever is longer.
- Patients who have participated in a clinical trial with repeated assessments (i.e. a
single assessment is not exclusionary) with the MATRICS Consensus Cognitive Battery
(MCCB) within the last 6 months prior to randomization.
- Patients who required a change in ongoing benzodiazepine or sleep medication dose or
regimen within the last 30 days prior to randomization.
- Use of systemic steroids within 30 days prior to randomization.
- Patients taking strong or moderate CYP3A4 inhibitors or inducers within the last 30
days prior to randomization. A list of strong or moderate CYP3A4 inhibitors and
inducers will be provided in the ISF.
- Patients who must or wish to continue the intake of restricted medications or herbal
remedies
- Patients who received treatment with medical devices (e.g. TMS, neurofeedback) for any
psychiatric condition within the last 3 months prior to randomization.
- Patients who have received electroconvulsive therapy (ECT) within 6 months prior to
randomization or repeated courses of ECT within 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) prior to randomization.
- Any suicidal ideation of type 4 or 5 in the 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) prior to randomization.
- Any of the following, in the judgment of the investigator:
- Clinically significant finding of the physical examination, vital signs
(including blood pressure (BP) and pulse rate (PR)), ECG or laboratory value (as
measured by the central laboratory) that would jeopardize the patient's safety
while participating in the trial or their capability to participate in the trial.
- Symptomatic/unstable/uncontrolled or clinically relevant concomitant disease or
any other clinical condition that would jeopardize the patient's safety while
participating in the trial or capability to participate in the trial.
- Significant or unstable physical condition that may require change in medication
or hospitalization that would impact cognitive function, or planned elective
surgery requiring general anesthesia during the study period.
- Patients for which cognitive or other impairment (including severe hearing
impairment) or symptom severity compromises the ability to perform the CCT or
assessments related to cognitive outcome measures.
- Severe renal impairment defined as an eGFR < 30mL/min/1.73m² in the Visit 1 central
lab report.
- Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT),
or alkaline phosphatase above 3 times upper limit of normal as determined in the Visit
1 central lab report.
- Known history of HIV infection based on review of medical history and/or a positive
result for ongoing Hepatitis B or C infection on the Visit 1 central lab report.
- 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,
squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
- Hb less than 120 g/L (12g/dL) in men or 115 g/L (11.5g/dL) in women at Visit 1.
- History of hemoglobinopathy such as thalassemia major or sickle-cell anemia.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
- Significant history of drug abuse disorder within the last 6 months prior to informed
consent (including alcohol, as defined in DSM-5-substance use disorder or in the
opinion of the investigator), or a positive urine drug screen at Visit 1. Note:
Patients testing positive for cannabis on urine drug screen at Visit 1 may be
re-tested once if there is a reasonable explanation and expectation that the patient
will not test positive again on re-test, and at the discretion of the investigator.
- Patients who are not fluent in the language of the batteries/questionnaires which will
be used in the country.
- Patient who did not make an effortful attempt to complete the cognition battery at
Visit 1 in the clinical judgement of the investigator.
- Patients that previously received treatment in any study with BI 425809.
- Patients with an allergy to BI 425809 and/or any of the excipients (including lactose)
or placebo ingredients. A list of BI 425809 and placebo ingredients will be provided
in the ISF.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
