Study of Systemic and Ocular Safety and Pharmacokinetics of BI 409306 in Patients With Schizophrenia, Alzheimer's Disease, and Healthy Volunteers

Inclusion criteria:

- Schizophrenia group:

- Patients with established diagnoses of schizophrenia (per Diagnostic and
Statistic Manual of Mental Disorder, version V) with the all of the following
clinical features:

- Clinically stable and are in the residual (non-acute) phase of their illness
for at least 8 weeks prior to randomisation

- Current antipsychotic and concomitant psychotropic medications must meet the
criteria below:

- 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

- 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

- 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.

- 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)

- Have no more than a moderate severity rating on positive formal thought
disorder (PANSS, positive syndrome Conceptual Disorganization item score <=
4)

- Have a minimal level of extrapyramidal symptoms (Simpson-Angus Scale total
score < 6) and depressive symptoms (PANSS, general psychopathology syndrome
Depression item score <= 4)

- Male or female patients age 18 to 55 years.

- Alzheimer's Disease group:

- Patients with diagnosis of mild Alzheimer's Dementia based on DSM-V and in
accordance with the recommendations from the National Institute on
Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's
disease.

- Mini-Mental State Examination (MMSE) score of 18-26.

- Male or female patients age 55 to 85 years, who have not been taking acetyl
cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and/or memantine
for at least 3 months or on stable dose of acetyl cholinesterase inhibitors
(donepezil, galantamine, rivastigmine) and/or memantine at least 3 months before
randomization.Patients older than 85 years may be included based on an acceptable
general health status, (e.g. concomitant diseases, physical capability to follow
the required study procedures [visits etc.]) per investigators judgement.

- Availability of a pre-existing cranial computer tomography (CCT) or magnetic
resonance imaging (MRI) scan of the brain (initiation of radiological imaging is
not required) not older than one year prior to screening; if not available, a CCT
must be performed at screening. Results of radiological brain imaging must be
compatible with Diagnosis of Alzheimer's Disease and exclusion of relevant signs
indicative of potential vascular dementia (see also exclusion criteria).

- If needed, a caregiver may be present during site activities.

- Age-comparable male or female healthy volunteers age 18 to 85 years. Healthy
volunteers older than 85 years may be included based on an acceptable general health
status, (e.g. concomitant diseases, physical capability to follow the required study
procedures [visits etc.]) per investigators judgement:

- After 10 patients with schizophrenia (as described above) are entered into the
study, the median age of the group will be computed. Five healthy volunteers at
or below the median age but greater than 18 years old and five healthy volunteers
above the median but less than 55 will be entered into the study.

- Similarly, after 10 patients with AD are entered, the median age will be
computed. Five healthy volunteers at or below the median age but greater than 55
years old and five healthy volunteers above the median but less than 85 will be
entered into the study.

- Subjects must exhibit reliability and physiologic capability to comply with all
protocol procedures.

- Signed and dated written informed consent by date of Visit 1 in accordance with Good
Clinical Practice and the local legislation. If the patient needs a legal
representative, then this legal representative must give written informed consent as
well.

Exclusion criteria:

- Presence of active ocular conditions with or without visual impairment due to any
causes (e.g. cataract, chorioretinal macular lesion, amblyopia, active diabetic
retinopathy, uncontrolled glaucoma, active inflammation or infection, etc.) in one eye
or both eyes at the screening phase.

- Planned ocular treatment (e.g. intravitreal antivascular growth factor,
corticosteroids) or surgery during the study period.

- Current or planned use of ocular or systemic corticosteroids.

- Current or planned use of medications known to be toxic to the retina, lens, optic
nerve

- Subjects treated with more than two antipsychotic medications (including more than two
dosage forms).

- Dementia in Alzheimers Disease patients, secondary to other disorders (based on
clinical data and/or current laboratory findings and/or on a pre-existing cranial MRI
or CCT).

- Neurological disease (other than Dementia of Alzheimer Type such as: Lewy body
dementia - primary diagnosis, Huntington's disease, Parkinson's Disease encephalitis,
epilepsy, vascular or multi-infarct dementia, stroke, congenital mental deficiency, or
multiple sclerosis), or mental retardation.

- Subjects needing to take long-acting hypnotics or anxiolytic (i.e. Diazepam).

- For AD patients, the following drugs are prohibited for 3 months prior to
randomization and for the duration of the trial:

- tricyclic antidepressants,

- antidepressants that are monoamine oxidase inhibitors,

- neuroleptics with moderate or greater anticholinergic potency (e.g.,
chlorpromazine, fluphenazine, loxapine, perphenazine, thioridazine),

- anticholinergic medications.

- Intake of St. John's wort, Carbamazepine and extracts from Ginko as they are
relevant CYP2C19 inducers.

- Substantial concomitant cerebrovascular disease (defined by a history of a
stroke/intracranial haemorrhagia temporally related to the onset of worsening of
cognitive impairment).

- Any suicidal ideation of type 4 or 5 in the Columbia Suicidal Severity Rating Scale
(C-SSRS) in the past 3 months.

- Any suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt,
aborted attempt, or preparatory acts or behavior).

- History or diagnosis of symptomatic and unstable/uncontrolled gastrointestinal,
hepatic, renal, respiratory, cardiovascular, metabolic, immunological, haematological
or hormonal disorders.

- For female subjects:

--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

- For male subjects: Men who are able to father a child, unwilling to be abstinent or
use adequate contraception.

- Known history, or new diagnosis of HIV infection.

- Significant renal disease (CLCR < 30 mL/min).

- Bodyweight < 50 kg.

- Indication of liver disease.

- History of neurologic (e.g. stroke, seizure without a clear and resolved etiology,
concussion accompanying loss of consciousness) or psychiatric condition.

- History of malignancy within the last 5 years, except for basal cell carcinoma.

- Planned elective surgery requiring general anaesthesia, or hospitalisation during the
study period.

- Significant history of drug dependence

- Clinically significant uncompensated hearing loss. Use of hearing aids is not allowed.

- Further exclusion criteria apply.