| Eligibility |
Inclusion Criteria:
1. Provide written informed consent form by subjects and subject's legal guardian or
legally acceptable representative.
2. The subjects and subject's legal guardian or legally acceptable representative have
the ability to understand the nature of the trial, agree to comply with the prescribed
medication and dosage regimens, complete the scheduled visits, report the adverse
events and concomitant medication to investigators, and to be reliably rated on
psychiatrically scales.
3. At the time of signing informed consent, 18 = age of the subject = 65.
4. Subjects who are diagnosed with schizophrenia according to Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and confirmed by
Mini International Neuropsychiatric Interview (MINI).
5. Subjects who are experiencing an acute exacerbation of psychotic symptoms and marked
deterioration of usual function as demonstrated by meeting ALL of the following
criteria at the screening and baseline visit:
? PANSS total score = 70;
- Score = 4 on at least 2 of the following PANSS items :
( P2 Conceptual disorganization, P3 Hallucinatory behavior, P6 Suspiciousness /
persecution, G9 Unusual thought content ) ? CGI-S score = 4;
6. Subjects willing to discontinue all prohibited psychotropic medications to meet
protocol-required washouts prior to and during the trial period.
Exclusion Criteria:
1. From ICF to 30 days after the last dose, females of childbearing potential and male
subjects who are not willing or cannot practice contraceptive methods.
2. Females who are pregnant or breastfeeding.
3. Subjects who have been hospitalized for > 21 days for the current acute episode at the
time of the Baseline visit, excluding hospitalization for psychosocial reasons.
4. Subjects with improvement of = 30% in total PANSS score between the screening and
baseline assessment. Improvement in PANSS score= (score at screening-score at
baseline)/ (score at screening-30)*100%.
5. Subjects with schizophrenia who are considered resistant/refractory to antipsychotic
treatment by history of failure to respond to 2 adequate different antipsychotic
medications with a minimum of 6 weeks at clinically efficacious tolerated doses.
Subjects who have a systemic treatment of clozapine.
6. Subjects with a current DSM-IV-TR Axis I diagnosis (including but not limited to):
schizoaffective disorder, MDD, bipolar disorder, post-traumatic stress disorder,
anxiety disorders, delirium, dementia, amnestic or other cognitive disorders.
7. Subjects with a current DSM-IV-TR Axis II diagnosis: borderline, paranoid, histrionic,
schizotypal, schizoid, or antisocial personality disorders.
8. Subjects who present a serious risk of suicide:
? Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 or 5 and meeting
the criteria for this C-SSRS Item 4 or 5 occurred within the last 6 months; OR
? Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items and meeting
the criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the
last 2 years; OR
? Subjects who, in the opinion of the investigator, present a serious risk of suicide
9. Subjects with clinically diagnosed tardive dyskinesia, as determined by a score of = 3
in Item 8 of the AIMS at the Screening visit.
10. Subjects with a score of 5 in the BARS global clinical assessment of akathisia at
Screening or Baseline.
11. Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the
180 days prior to Screening Visit; including alcohol and benzodiazepines, but
excluding caffeine and nicotine.
12. Subjects with uncontrolled thyroid disease and/or abnormal free thyroxine (FT4)
examination results at Screening, unless it has been confirmed by the investigator
that the condition has been stabilized by medication > 90 days before screening
13. Subjects with type I diabetes or uncontrolled type II diabetes. Subjects with type II
diabetes may be eligible for the trial if their condition is stable as determined by
satisfying ALL of the following criteria:
- HbA1c < 7.0%, AND
- Glucose must be = 125 mg/dL or = 6.94 mmol/L (fasting) or < 200 mg/dL or < 11.1
mmol/L (non-fasting) at Screening. If the non-fasting glucose is = 200 mg/dL or =
11.1 mmol/L, subjects must be retested in a fasted state and the retest value
must be = 125 mg/dL or = 6.94 mmol/L, AND
- Subjects have maintained a stable regimen of oral anti-diabetic medication(s) for
at least 28 days prior to screening or diabetes has been well-controlled by diet
for at least 28 days prior to screening, AND
- Subjects have not had any hospitalizations within the 12 months prior to
screening due to diabetes or complications related to diabetes, AND
- Subjects whose diabetes is not newly diagnosed during screening for the trial.
14. Subjects with uncontrolled hypertension (diastolic blood pressure > 95 mmHg in any
position) or symptomatic hypotension, or orthostatic hypotension which is defined as a
decrease of = 30 mmHg in systolic blood pressure and/or a decrease of = 20 mmHg in
diastolic blood pressure after at least 3 minutes standing compared to the previous
supine blood pressure, OR development of symptoms.
15. Subjects with a history of ischemic heart disease or history of myocardial infarction,
congestive heart failure (whether controlled or uncontrolled), angioplasty, stenting,
or coronary artery bypass surgery.
16. Subjects who have a history or severe organic disease of vital organs (including but
not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic,
hematologic, or immunologic disease).
17. Subjects with epilepsy or a history of seizures, except for a single seizure episode,
for instance childhood febrile seizure and post traumatic or alcohol withdrawal.
18. The following laboratory test and ECG results are exclusionary:
1) Platelets = 75,000/mm3 (= 75 x 109 /L) 2) Hemoglobin = 9 g/dL (90 g/L) 3) Neutrophils =
1,000/mm3 (1 x 109 /L) 4) AST or ALT > 2 × ULN 5) CPK > 3 × ULN 6) Creatinine = 2 mg/dL
(176.8 µmol/L) 7) HbA1c = 7.0% 8) QTc = 450 msec (for males) or = 470 msec (for females) in
ECG 19. Subjects who received ECT within 60 days of screening. 20. Subjects with a history
of neuroleptic malignant syndrome (NMS). 21. Subjects with a history of true allergic
response (ie, not intolerance) to more than one class of medications.
22. Subjects who participated in a clinical trial within the last 90 days or who
participated in two or more clinical trials within the past year.
23. Any subject who, in the opinion of the investigator, should not participate in the
trial.
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