A Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of ASP6981 in Subjects With Schizophrenia

Inclusion Criteria: * Subject has a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria. * Subject is considered operationally stable if the subject has a low to moderate positive symptom score and moderate negative symptom score on the PANSS (Positive and Negative Syndrome Scale): no more than moderate rating on more than 2 PANSS items P1, P2, P3, P5, P6; no more than moderate severity rating for the negative items, N1, N2, N3, N4, N5, N6, N7; total PANSS score no more than 80. * Subject must be in ongoing maintenance antipsychotic therapy (i.e., second generation antipsychotics other than clozapine oral or depot), on a stable (less than or equal to 25% change in dose) medication treatment regimen (approved oral or depot formulations of risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone; up to 2 permitted on condition that the second medication is not required to control treatment resistance or intractable psychotic symptoms) for more than or equal to 2 months for oral formulations or more than or equal to 3 months for depot formulations prior to screening, including concomitant psychotropic medications, such as, trazodone and zolpidem for sleep. * Subject has a body mass index (BMI) range of 18.5 to 40.0 kg/m2, inclusive, and weighs at least 50 kg. * Subject has a negative urine drug screen for drugs of abuse. * Female subject must not donate ova starting at screening and throughout the study period, and for 28 days after the final study drug administration. * Female subject must agree not to breastfeed 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 are of childbearing potential is eligible if: * The male subject agrees to use a male condom starting at screening and continue throughout the study period and for 90 days after the final study drug administration. * The male subject has not had a vasectomy or is not sterile, as defined above, their female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continuing throughout study treatment and for 90 days after the male subject receives their 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. * Male subject must not donate sperm starting at screening and 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 ESV. Exclusion Criteria: * Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening. * Subject has a known or suspected hypersensitivity to ASP6981 or any components of the formulation used. * Subject has had previous exposure with ASP6981. * Subject has a history of heavy smoking (use more than 40 cigarettes/2 packs per day) or a user of nicotine replacement therapy (includes nicotine patches, Chantix or similar therapeutic agents) in the past 3 months prior to admission to the clinical unit (day -3). * Subject has a history of suicide attempt or suicidal behavior within 2 years prior to screening. Any suicidal ideation that meets criteria at a level of 4 or 5 by using C-SSRS within the last 3 months or who is at significant risk to commit suicide will be excluded. * Subject has any clinically significant liver chemistry test result (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], alkaline phosphatase \[ALP\], gamma glutamyl transferase, total bilirubin \[TBL\]) or a result greater than 1.5 x greater than upper limit of normal (ULN). In such a case, the assessment may be repeated once. * Subject has any history of allergic conditions deemed clinically significant. * Subject has any history or evidence of any clinically significant cardiovascular, gastro-intestinal endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric (other than schizophrenia or schizoaffective disorder), renal and/or other major disease or malignancy. * Subject has a history of being diagnosed with moderate or severe tardive dyskinesia, bipolar disorder, major depressive disorder, personality disorders, neuroleptic malignancy syndrome or anxiety disorder. * Subject has any clinically significant abnormality of the physical examination, ECG and protocol-defined clinical laboratory tests. * Subject has a mean pulse lower than 40 or greater than 100 bpm; resting systolic blood pressure (SBP) lower than 90 or greater than 180 mmHg, or a resting diastolic blood pressure (DBP) greater than 100 mmHg at screening and on day -3 (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically). If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken at screening and on day -3. * Subject has a mean QT interval using Fridericia's correction (QTcF) of greater than 450 ms (for male subjects) and greater than 470 ms (for female subjects). If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken at screening and on day -3. * Subject uses any prescribed (including current treatment with anticholinergic medications such as benztropine, biperiden, procyclidine, and trihexyphenidyl) or nonprescribed drugs (including vitamins, natural and herbal remedies, e.g., valerian) in the 2 weeks prior to study drug administration until the ESV, except for: * Approved second generation antipsychotics (risperidone, quetiapine, olanzapine, ziprasidone, brexpiprazole, aripiprazole, paliperidone or lurasidone), or * Approved intermittent use of short-acting hypnotic agents trazodone or zolpidem (no less than 12 hours prior to dosing), or * Approved intermittent use of anticholinergic compounds, or * Approved use of concomitant medication for the treatment of hypertension, hyperlipidemia or diabetes mellitus, or * Occasional use of acetaminophen (up to 2 g/day), or * Hormonal contraceptives, or * Hormone replacement therapy. * Subject has a history of consuming more than: 14 units of alcoholic beverages per week for male subjects or 7 units of alcoholic beverages per week for female subjects within 6 months prior to screening or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: 1 unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits/hard liquor) or the subject tests positive for alcohol or drugs of abuse at screening or at admission to the clinical unit (day -3 of period 1). Subject tests positive for benzodiazepines at admission to the clinical unit (day -3 of period 1). * Subject who is unable to refrain from smoking or drinking coffee for 3 hours prior to the Cogstate and EEG testing. * Subject has used any strong CYP3A inhibitors (e.g., but not limited to: boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole) and/or has consumed grapefruit, grapefruit-containing products, Seville orange or Seville orange-containing products within 72 hours prior to admission to the clinical unit (day -3 of period 1). * Subject regularly uses any inducer of CYP3A metabolism (e.g., but not limited to: carbamazepine, phenytoin, rifampin, St. John's Wort, bosentan, efavirenz, etravirine, modafinil, nafcillin, amprenavir, aprepitant, armodafinil, clobazamechinacea, pioglitazone, prednisone, rufinamide, vemurafenib) in the 3 months prior to admission to the clinical unit (day -3 of period 1). * Subject has a positive serology test for hepatitis B surface antigen, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies or human immunodeficiency virus antibodies type 1 or 2. * Subject who has had electroconvulsive therapy within the 6 months prior to screening. * Subject has a history of seizures or of a condition with risk of seizures; as an exception, a history of 1 febrile seizure in childhood will not exclude a subject. * Subject has a history of head injury with clinically significant sequelae. * Subject experienced an acute exacerbation of schizophrenia requiring hospitalization or an increase in antipsychotic medication (with reference to drug or dose) within the last 2 months prior to screening. * Subject has hearing loss, is unable to detect 1000 Hz tones presented at 40 dB. * Subject has a condition which makes the subject unable to complete or perform the EEG assessments defined in the study (e.g., dreadlocks), during the study screening period. * Subject has a history of spine surgery (with intact dura mater) in the past year and/or a history of brain and/or spinal cord injury. * Subject has a condition which makes the subject unable to complete the study cognitive assessments defined in the study, during the study screening period. * Subject has any condition, which makes the subject unsuitable for study participation. * Subject has participated in any study or has been treated with any investigational drugs within 28 days or 5 half-lives whichever is longer, prior to screening.