| 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)
who is 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. Be 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, 21-item version (HAM-D-21) =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 14 days prior to study drug dosing, throughout the study, and for at
least 200 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 200 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 met 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
1) caffeine or nicotine in the past 6 months prior to screening, or 2) 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
psychiatric illness.
3. Patients who received any of following treatment:
- 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
more than 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)
> 2x 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 >2x 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 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. Subject 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. Subject who had severe course of COVID-19 (i.e., hospitalization, extracorporeal
membrane oxygenation (ECMO), and/or mechanically ventilated).
15. Malignancies within 5 years with the exception of cured basal cell or squamous cell
skin cancer or in situ cervical cancer prior to screening.
16. History or current diagnosis of epilepsy or convulsive disorder other than a single
childhood febrile seizure.
17. History or current diagnosis of Parkinson's diseases, Dementia with Lewy Bodies or
other Dementia-related psychosis.
18. Receipt of another investigational product within 1 month, or 5 half-lives of the
other investigational product, whichever is longer, prior to screening.
19. 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.
20. Clinical Laboratory at screening indicating white blood cells <3x109/L, or neutrophils
<1.5x109/L or platelets < 80 x109/L.
21. Has a prolactin laboratory value = 100 ng/ml at screening.
22. Human immunodeficiency virus (HIV) test positive.
23. 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 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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