A Study to Assess the Safety and Efficacy of ASP4345 as Add-on Treatment for Cognitive Impairment in Subjects With Schizophrenia on Stable Doses of Antipsychotic Medication

Participants will receive oral doses of ASP4345 or matching placebo QD (once daily) for 12
weeks. All participants will be administered the first dose of blinded study drug at the site
following randomization and provided with web-based applications that provide supplemental
cognitive training and record treatment compliance. Participants will return to the clinic
weekly for safety, efficacy, and/or pharmacokinetic procedures. Participants will continue
the participant's antipsychotic treatment for the entire study and will be followed for 14
days after the participant's last dose of study drug.

Inclusion Criteria:

- Subject has a diagnosis of schizophrenia or schizoaffective disorder according to the
Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria and
confirmed by the Mini-International Neuropsychiatric Interview version 7.02

- Subject has a stable clinical course as suggested by the following:

- no psychiatric hospitalization within the last 4 months,

- no symptom-related changes in psychotropic medications (as defined in the
concomitant medication section) within 4 weeks prior to baseline for oral
medications and within 2 months for depot medications,

- and core positive symptoms no worse than moderate in severity and no evidence of
a current severe major depressive episode (moderately severe depression is
allowed)

- Subject has a stable living situation

- Subject's extrapyramidal symptoms are no worse than mild in severity

- Subject must be in ongoing maintenance (i.e., at least 4 weeks prior to day 1 for oral
medications and within 2 months for depot medications) on up to 2 antipsychotic
therapies (oral or depot) other than clozapine

- Subject has a body mass index range of 18.5 to 45.0 kg/m2

- Female subject must either:

- Be of nonchildbearing potential:

- Postmenopausal (defined as at least 1 year without menses) prior to screening or

- Documented as surgically sterile

- Or, if of childbearing potential

- Agrees not to try to become pregnant during the study and for 28 days after the
final study drug administration

- And has a negative blood pregnancy test at screening and a negative urine
pregnancy test at day 1,

- and if heterosexually active, agrees to consistently use 1 form of highly
effective birth control starting at screening and throughout the study period and
for 28 days after the final study drug administration

- Female subjects must agree not to breastfeed starting at screening and throughout the
study period, and for 28 days after the final study drug administration

- Female subject must not donate ova starting at screening and throughout the study
period, and for 28 days after the final study drug administration

- A sexually active male subject with female partner(s) who is of childbearing potential
is eligible if:

- Agrees to use male condom starting at screening and throughout the study period,
and for 28 days after the final study drug administration

- Male subject must not donate sperm starting at screening and throughout the study
period, and for 28 days after the final study drug administration

- Male subject with a pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the study period and for 90 days after the final study drug
administration

- Subject agrees not to participate in another interventional study while participating
in the present study, defined as signing the informed consent form until completion of
the last study visit

- Subject has a negative urine drug screen for drugs of abuse at screening and day 1,
excluding cannabis and documented prescribed benzodiazepines

Exclusion Criteria:

- Subject has a known or suspected hypersensitivity to ASP4345 or any components of the
formulation

- Subject has had previous exposure with ASP4345

- Subject has a history of suicide attempt or suicidal behavior within 1 year prior to
screening or has any suicidal ideation that meets criteria at a level of 4 or 5 by
using the Columbia Suicide Severity Rating Scale (C-SSRS) or who is at significant
risk to commit suicide

- Subject has any clinically significant liver chemistry test result (aspartate
aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) or a
result > 1.5 times above the upper limit of normal (ULN) at screening or repeated
within

1 week prior to potential randomization (day 1). In such a case, the assessment may be
repeated once

- Subject has any history or evidence of any clinically significant allergic,
cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic,
metabolic, urologic, pulmonary, neurologic, dermatologic, history of seizure disorder,
renal and/or other major disease or malignancy

- Subject has any clinically significant abnormality of the physical examination,
electrocardiogram (ECG) and clinical laboratory tests at screening or at admission to
the study (day 1)

- Subject has known kidney disease and a glomerular filtration rate (GFR) < 60 mL/min
per meter squared at screening and subjects will be discontinued from treatment only
for decreases in the GFR that are clinically relevant

- Subject has a resting systolic blood pressure > 180 mmHg or < 90 mmHg, and a resting
diastolic blood pressure > 100 mmHg at screening. These assessments may be repeated
once, after a reasonable time period, at the investigator's discretion (but within the
screening period)

- Subject has a mean corrected QTcF > 450 msec (for male subjects) and > 470 msec (for
female subjects) at screening or at randomization. If the mean QTcF exceeds the limits
above, one additional triplicate ECG can be taken on day 1

- Subject has a history in the 6 months prior to screening of consuming more than 14
units of alcoholic beverages per week for males and more than 7 units of alcoholic
beverages per week for females. (Note 1 unit = 12 ounces of beer, 4 ounces of wine, or
1 ounce of spirits)

- Subject is currently using prohibited medications and is unable to washout, including
over-the-counter products and agrees not to consume grapefruit and/or grapefruit juice

- Subject is currently using clozapine for treatment of schizophrenia

- Subject has a positive test for hepatitis B surface antigen (HBsAg), hepatitis A virus
antibodies (immunoglobulin M) (anti-HAV [IgM]) or hepatitis C virus antibodies (anti-
HCV) at Screening or has history of a positive test for human immunodeficiency virus
type 1(HIV-1) and/or type 2 (HIV-2)

- Subject who has had electroconvulsive therapy within the 6 months prior to screening.

- Subject has a history of head injury with clinically significant sequelae, including
loss of consciousness for 1 hour or greater

- Subject has received investigational study drug within 28 days or 5 half-lives,
whichever is longer, prior to screening