| Eligibility |
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, social
worker) considered reliable by the Investigator to help ensure compliance with
study visits and to alert staff of any issues of concern.
3. Have a stable place of residence for the 3 months prior to screening and
throughout the study.
4. Male or female =18 to =65 years of age who meets diagnostic criteria for
schizophrenia or schizoaffective disorder according to the Diagnostic and
Statistical Manual of Mental Disorders Fifth Edition (DSM-V) for at least 1 year
before screening.
5. Have been on a stable dose of oral antipsychotic medication(s) other than
risperidone, paliperidone, clozapine, ziprasidone, or thioridazine for at least 4
weeks prior to screening.
6. Be clinically stable based on clinical assessments and a Positive and Negative
Syndrome 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) must
have a negative pregnancy test result at both screening and baseline. Female
patients must meet 1 of the following 3 conditions: (i) postmenopausal for at
least 12 months without an alternative medical cause, (ii) surgically sterile
(hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or bilateral
tubal occlusion) based on patient report, or (iii) if of childbearing potential
(WOCBP) and heterosexually active, practicing or agree to practice a highly
effective contraception method of birth control. Highly effective methods of
birth control include an intrauterine device (IUD), intrauterine
hormone-releasing system (IUS), and contraceptives (oral, skin patches, or
implanted or injectable products) using combined or progestogen-only hormonal
contraception associated with inhibition of ovulation. A vasectomized male
partner is an acceptable birth control method if the vasectomized partner is the
sole sexual partner of the female patient and the vasectomized partner has
received medical confirmation of surgical success. Highly effective methods of
birth 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) visit
to minimize the risk of pregnancy.
11. Sexually active fertile male patients must be willing to use acceptable
contraception methods (such as double barrier methods of a combination of male
condom with either cap, diaphragm or sponge with spermicide) from study drug
dosing, throughout the study, and for at least 30 days after the EOS visit if
their partners are women of childbearing potential.
Exclusion Criteria:
- Patients will be excluded from study entry if 1 or more exclusion criteria are present at
screening:
1. Primary and active DSM-V Axis I diagnosis other than schizophrenia or Schizoaffective
disorder.
2. Patients who meet DSM-V criteria for substance abuse (moderate or severe), or test
positive for a drug of abuse or alcohol at screening or baseline with the exception of
test positive for barbiturate or benzodiazepine which can be accounted for by
documented prescriptions from a treating physician as a part of the treatment for the
patient'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 3
months, 1-month depot formulation of risperidone (PERSERIS KIT®) or 9-hydroxy
risperidone (INVEGA SUSTENNA®) within 1 year, or 3-month depot formulation of
9-hydroxy risperidone (INVEGA TRINZA®) within 2 years before screening. Use of
other long-acting injectable for the treatment of schizophrenia within 4 weeks
before screening.
- Use of nonselective or irreversible monoamine oxidase inhibitor (MAOI)
antidepressants within 30 days before screening. Patients on other
antidepressants should be excluded as well unless the dose has been stable for at
least 30 days before screening.
- Use of strong inducers or inhibitors of CYP3A4 or P-glycoprotein (P-gp) within 2
weeks 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, or
any of their excipients (oral risperidone tolerability test will be completed during
the screening period, approximately14 days but no less than 9 days prior to dosing,
for patients without documented evidence [medical record or written statement from a
licensed medical practitioner who has treated the patient] of tolerating risperidone
or paliperidone, and patients who show an allergic reaction to this test will be
excluded from the study).
5. Patients who pose a significant risk of a suicide attempt based on history or the
Investigator's judgment; answer "yes" to Suicidal Ideation items 4 or 5 on the
Columbia 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 6
months as measured by the C-SSRS at screening; or are at imminent risk of suicide or
violent behavior based on the Investigator's clinical assessment or the C-SSRS
assessment of lifetime suicidal ideation or behavior at screening.
6. Any one or more of the following 3 conditions: (i) clinically significant liver
dysfunction, (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 ALT
or AST levels are between 2x and 3x ULN in the first screening test and the elevation
may be caused by non-specific reasons in the judgment of the Investigator, a second
test can be performed after one week. If the repeated ALT or AST levels are still >2 x
ULN, the patient must be excluded from the study. Patients who are HCV antibody
reactive but confirmed HCV RNA not detected may be enrolled, if this condition has
been previously considered stable without treatment or after the completion of
appropriate treatment, and liver function is normal.
7. History of symptomatic orthostatic hypotension or with a decrease of = 20 mmHg in
systolic 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 supine
position for at least 5 minutes or SBP less than 105 mmHg in a supine position at
screening 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 filtration
rate < 80 mL/min).
10. History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia; history of
severe akathisia or extra-pyramidal reactions such as dystonia with previous use of
risperidone or other neuroleptic treatments; score = 3 on the Global Clinical
Assessment 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 to
participate 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 confirmed
infection by appropriate laboratory test within the last 30 days prior to screening or
on admission.
14. Patient who had severe course of COVID-19 (i.e., hospitalization, extracorporeal
membrane oxygenation (ECMO), and/or mechanically ventilated).
15. Patients who have received COVID-19 vaccines within the last 14 days prior to baseline
or plan to get vaccinated within 30 days after dosing.
16. Malignancies within 5 years with the exception of cured basal cell or squamous cell
skin cancer or in situ cervical cancer prior to screening.
17. History or current diagnosis of epilepsy or convulsive disorder other than a single
childhood febrile seizure.
18. History or current diagnosis of Parkinson's diseases, Dementia with Lewy Bodies or
other Dementia-related psychosis.
19. Receipt of another investigational product within 1 month, or 5 half-lives of the
other investigational product, whichever is longer, prior to screening.
20. Donation or blood collection of > 1 unit (approximate 450 mL) of blood (or blood
products) 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 or
baseline visits which, in the opinion of the Investigator, may endanger the patient or
interfere with the endpoints of the study. If the results of clinical laboratory
testing (unless specified) are outside normal reference ranges, the patient may be
enrolled but only if these findings are determined not to be clinically significant by
the Investigator. This determination must be recorded in the patient's source
documents.
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