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

Inclusion Criteria:

• Subject has a diagnosis of schizophrenia or schizoaffective disorder according tothe Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria andconfirmed 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 theconcomitant medication section) within 4 weeks prior to baseline for oralmedications and within 2 months for depot medications,

• and core positive symptoms no worse than moderate in severity and no evidenceof a current severe major depressive episode (moderately severe depression isallowed)

• 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 fororal medications and within 2 months for depot medications) on up to 2 antipsychotictherapies (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 screeningor

• Documented as surgically sterile

• Or, if of childbearing potential

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

• And has a negative blood pregnancy test at screening and a negative urinepregnancy test at day 1,

• and if heterosexually active, agrees to consistently use 1 form of highlyeffective birth control starting at screening and throughout the study periodand for 28 days after the final study drug administration

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

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

• A sexually active male subject with female partner(s) who is of childbearingpotential is eligible if:

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

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

• Male subject with a pregnant or breastfeeding partner(s) must agree to remainabstinent or use a condom for the duration of the pregnancy or time partner isbreastfeeding throughout the study period and for 90 days after the final study drugadministration

• Subject agrees not to participate in another interventional study whileparticipating in the present study, defined as signing the informed consent formuntil 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 ofthe formulation

• Subject has had previous exposure with ASP4345

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

• Subject has any clinically significant liver chemistry test result (aspartateaminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) or aresult > 1.5 times above the upper limit of normal (ULN) at screening or repeatedwithin

1 week prior to potential randomization (day 1). In such a case, the assessment maybe 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 seizuredisorder, 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 admissionto the study (day 1)

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

• Subject has a resting systolic blood pressure > 180 mmHg or < 90 mmHg, and a restingdiastolic blood pressure > 100 mmHg at screening. These assessments may be repeatedonce, after a reasonable time period, at the investigator's discretion (but withinthe screening period)

• Subject has a mean corrected QTcF > 450 msec (for male subjects) and > 470 msec (forfemale subjects) at screening or at randomization. If the mean QTcF exceeds thelimits 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 14units of alcoholic beverages per week for males and more than 7 units of alcoholicbeverages 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/orgrapefruit juice

• Subject is currently using clozapine for treatment of schizophrenia

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

• Subject who has had electroconvulsive therapy within the 6 months prior toscreening.

• Subject has a history of head injury with clinically significant sequelae, includingloss 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