Study to Evaluate the PK Profiles of LY03010 in Patients With Schizophrenia or Schizoaffective Disorder

Inclusion Criteria:

• To participate in the study, patients must meet all inclusion criteria at screening:

1. Capable of giving informed consent and complying with study procedures.
2. Have an identified support person (e.g., family member, case worker, socialworker) considered reliable by the Investigator to help ensure compliance withstudy visits and to alert staff of any issues of concern.
3. Have a stable place of residence for the 3 months prior to screening andthroughout the study.
4. Male or female ≥18 to ≤65 years of age who meets diagnostic criteria forschizophrenia or schizoaffective disorder according to the Diagnostic andStatistical Manual of Mental Disorders Fifth Edition (DSM-V) for at least 1 yearbefore screening.
5. Have been on a stable dose of oral antipsychotic medication(s) other thanrisperidone, paliperidone, clozapine, ziprasidone, or thioridazine for at least 4weeks prior to screening.
6. Be clinically stable based on clinical assessments and a Positive and NegativeSyndrome Scale (PANSS) total score ≤75 as well as a PANSS HATE (hostility,anxiety, tension and excitement) subtotal score <16 at screening.
7. Clinical Global Impression-Severity (CGI-S) score of 1 to 4, inclusive.
8. For patients with schizoaffective disorder only: Young Mania Rating Scale (YMRS) ≤12 and Hamilton Rating Scale for Depression, 17-item version (HAM-D) ≤12.
9. Body mass index (BMI) ≥17.0 and ≤37 kg/m2; body weight ≥50 kg.
10. All female patients (childbearing potential and non-childbearing potential) musthave a negative pregnancy test result at both screening and baseline. Femalepatients must meet 1 of the following 3 conditions: (i) postmenopausal for atleast 12 months without an alternative medical cause, (ii) surgically sterile (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or bilateraltubal occlusion) based on patient report, or (iii) if of childbearing potential (WOCBP) and heterosexually active, practicing or agree to practice a highlyeffective contraception method of birth control. Highly effective methods ofbirth control include an intrauterine device (IUD), intrauterinehormone-releasing system (IUS), and contraceptives (oral, skin patches, orimplanted or injectable products) using combined or progestogen-only hormonalcontraception associated with inhibition of ovulation. A vasectomized malepartner is an acceptable birth control method if the vasectomized partner is thesole sexual partner of the female patient and the vasectomized partner hasreceived medical confirmation of surgical success. Highly effective methods ofbirth control must be used for at least 21 days prior to study drug dosing,throughout the study, and for at least 30 days after the end-of-study (EOS) visitto minimize the risk of pregnancy.
11. Sexually active fertile male patients must be willing to use acceptablecontraception methods (such as double barrier methods of a combination of malecondom with either cap, diaphragm or sponge with spermicide) from study drugdosing, throughout the study, and for at least 30 days after the EOS visit iftheir partners are women of childbearing potential.

Exclusion Criteria:

• Patients will be excluded from study entry if 1 or more exclusion criteria are present atscreening:

1. Primary and active DSM-V Axis I diagnosis other than schizophrenia or Schizoaffectivedisorder.
2. Patients who meet DSM-V criteria for substance abuse (moderate or severe), or testpositive for a drug of abuse or alcohol at screening or baseline with the exception oftest positive for barbiturate or benzodiazepine which can be accounted for bydocumented prescriptions from a treating physician as a part of the treatment for thepatient's underlying medical conditions.
3. Patients who received any of the following treatment(s):

• Use of oral risperidone or paliperidone within 2 weeks before screening.
• Use of Clozapine, Thioridazine or Ziprasidone within 4 weeks before screening.
• Use of 2-week depot formulation of risperidone (RISPERDAL CONSTA®) within 3months, 1-month depot formulation of risperidone (PERSERIS KIT®) or 9-hydroxyrisperidone (INVEGA SUSTENNA®) within 1 year, or 3-month depot formulation of 9-hydroxy risperidone (INVEGA TRINZA®) within 2 years before screening. Use ofother long-acting injectable for the treatment of schizophrenia within 4 weeksbefore screening.
• Use of nonselective or irreversible monoamine oxidase inhibitor (MAOI)antidepressants within 30 days before screening. Patients on otherantidepressants should be excluded as well unless the dose has been stable for atleast 30 days before screening.
• Use of strong inducers or inhibitors of CYP3A4 or P-glycoprotein (P-gp) within 2weeks or 5 half- lives, whichever is longer, before screening.
• Electroconvulsive therapy within 60 days before screening.

4. Known or suspected hypersensitivity or intolerance of risperidone, paliperidone, orany of their excipients (oral risperidone tolerability test will be completed duringthe screening period, approximately14 days but no less than 9 days prior to dosing,for patients without documented evidence [medical record or written statement from alicensed medical practitioner who has treated the patient] of tolerating risperidoneor paliperidone, and patients who show an allergic reaction to this test will beexcluded from the study).
5. Patients who pose a significant risk of a suicide attempt based on history or theInvestigator's judgment; answer "yes" to Suicidal Ideation items 4 or 5 on theColumbia Suicide Severity Rating Scale (C-SSRS) for current or past 6 months on the "Baseline/Screening version" at screening; have had suicidal behavior in the last 6months as measured by the C-SSRS at screening; or are at imminent risk of suicide orviolent behavior based on the Investigator's clinical assessment or the C-SSRSassessment of lifetime suicidal ideation or behavior at screening.
6. Any one or more of the following 3 conditions: (i) clinically significant liverdysfunction, (ii) hepatitis B surface antigen (HBsAg) positive, hepatitis C (HCV)positive, or (iii) a serum alanine transaminase (ALT) or aspartate transaminase (AST) > 2 x upper limit of normal (ULN) range; or a total bilirubin > 1.5 x ULN (if the ALTor AST levels are between 2x and 3x ULN in the first screening test and the elevationmay be caused by non-specific reasons in the judgment of the Investigator, a secondtest can be performed after one week. If the repeated ALT or AST levels are still >2 xULN, the patient must be excluded from the study. Patients who are HCV antibodyreactive but confirmed HCV RNA not detected may be enrolled, if this condition hasbeen previously considered stable without treatment or after the completion ofappropriate treatment, and liver function is normal.
7. History of symptomatic orthostatic hypotension or with a decrease of ≥ 20 mmHg insystolic blood pressure (SBP) or decrease of ≥10 mmHg in diastolic blood pressure (DBP) when changing from supine to standing position after having been in the supineposition for at least 5 minutes or SBP less than 105 mmHg in a supine position atscreening or prior to randomization.
8. Uncontrolled diabetes or hemoglobin A1c (HbAlc) level ≥7% at screening.
9. Indication of impaired renal function at Screening (estimated glomerular filtrationrate < 80 mL/min).
10. History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia; history ofsevere akathisia or extra-pyramidal reactions such as dystonia with previous use ofrisperidone or other neuroleptic treatments; score ≥ 3 on the Global ClinicalAssessment of the BARS or score ≥ 2 on the AIMS at screening
11. QTcF interval greater than 450 msec for males and 460 msec for females at screening,or other clinically significant ECG findings in the opinion of the Investigator.
12. Clinically significant past medical history (within 2 years) of gastrointestinal,cardiovascular, musculoskeletal, endocrine, hematologic, renal, hepatic,bronchopulmonary, neurologic, immunologic disorders, or drug hypersensitivity which,in the judgment of the Investigator, would interfere with the patient's ability toparticipate in the study.
13. Patient has clinical signs and symptoms consistent with Coronavirus disease 2019 (COVID-19), e.g., fever, dry cough, dyspnea, sore throat, fatigue or confirmedinfection by appropriate laboratory test within the last 30 days prior to screening oron admission.
14. Patient who had severe course of COVID-19 (i.e., hospitalization, extracorporealmembrane oxygenation (ECMO), and/or mechanically ventilated).
15. Patients who have received COVID-19 vaccines within the last 14 days prior to baselineor plan to get vaccinated within 30 days after dosing.
16. Malignancies within 5 years with the exception of cured basal cell or squamous cellskin cancer or in situ cervical cancer prior to screening.
17. History or current diagnosis of epilepsy or convulsive disorder other than a singlechildhood febrile seizure.
18. History or current diagnosis of Parkinson's diseases, Dementia with Lewy Bodies orother Dementia-related psychosis.
19. Receipt of another investigational product within 1 month, or 5 half-lives of theother investigational product, whichever is longer, prior to screening.
20. Donation or blood collection of > 1 unit (approximate 450 mL) of blood (or bloodproducts) or acute loss of blood during the 90 days prior to screening.
21. Clinical Laboratory at screening indicating white blood cells <3x109/L, or neutrophils <1.5x109/L or platelets < 80 x109/L.
22. Has a prolactin laboratory value ≥ 100 ng/ml at screening.
23. Human immunodeficiency virus (HIV) test positive.
24. Any clinical observation or clinical laboratory abnormality findings at screening orbaseline visits which, in the opinion of the Investigator, may endanger the patient orinterfere with the endpoints of the study. If the results of clinical laboratorytesting (unless specified) are outside normal reference ranges, the patient may beenrolled but only if these findings are determined not to be clinically significant bythe Investigator. This determination must be recorded in the patient's sourcedocuments.