Lurasidone Low-Dose - High-Dose Study Study

The primary purpose of this study is to evaluate the efficacy of lurasidone 20 mg/day in
subjects with an acute exacerbation of schizophrenia. This study will also evaluate the
efficacy and safety of lurasidone 80 mg/day and160 mg/day versus placebo in subjects who are
early non-responders (operationally defined per protocol) to lurasidone 80 mg/day.

Inclusion Criteria:

Subject provides written informed consent and is willing and able to comply with the
protocol in the opinion of the Investigator.

- Subject is ≥ 18 and ≤ 75 years of age, on the day of signing the informed consent.

- Subject meets DSM-IV-TR criteria for a primary diagnosis of schizophrenia [including
disorganized (295.10), paranoid (295.30), undifferentiated (295.90) subtypes] as
established by clinical interview (using the DSM-IV-TR as a reference and confirmed
using the SCID-CT). The duration of the subject's illness whether treated or
untreated must be ≥ 6 months.

- Subject has a PANSS total score ≥ 80 and a PANSS subscale score ≥ 4 (moderate) on 2
or more of the following PANSS subscale items: delusions, conceptual disorganization,
hallucinations, and unusual thought content at screening and baseline.

- Subject has a CGI-S score of ≥ 4 at screening and baseline.

- Subject has an acute exacerbation of psychotic symptoms (no longer than 2 months) and
marked deterioration of function from baseline (by history) or subject has been
hospitalized for the purpose of treating an acute psychotic exacerbation for 2
consecutive weeks or less immediately before screening.

Subjects who have been hospitalized for more than 2 weeks for reasons unrelated to acute
exacerbation can be included with concurrence from the Medical Monitor that such
hospitalization was for a reason other than acute relapse. For example, subjects in a long
term hospital setting who have an acute exacerbation and are transferred to an acute unit
are eligible for study entry.

- Subject is not pregnant (must have a negative serum pregnancy test at screening) or
nursing (must not be lactating) and is not planning pregnancy within the projected
duration of the study.

- Female subject of reproductive potential agrees to remain abstinent or use adequate
and reliable contraception throughout the study and for at least 30 days after the
last dose of lurasidone has been taken. In the Investigator's judgment, the subject
will adhere to this requirement.

Adequate contraception is defined as continuous use of either two barrier methods (eg,
condom and spermicide or diaphragm with spermicide) or a hormonal contraceptive.
Acceptable hormonal contraceptives include the following: a) contraceptive implant (such
as Norplant®) implanted at least 90 days prior to screening; b) injectable contraception
(such as medroxyprogesterone acetate injection) given at least 14 days prior to screening;
or c) oral contraception taken as directed for at least 30 days prior to screening.

Subjects who are of non-reproductive potential, ie, subject who is surgically sterile, has
undergone tubal ligation, or is postmenopausal (defined as at least 12 months of
spontaneous amenorrhea or between 6 and 12 months of spontaneous amenorrhea with follicle
stimulating hormone (FSH) concentrations within postmenopausal range as determined by
laboratory analysis) are not required to remain abstinent or use adequate contraception.

- Subject is able and agrees to remain off prior antipsychotic medication for the
duration of the study

- Subject has had a stable living arrangement at the time of screening and agrees to
return to a similar living arrangement after discharge. This criterion is not meant
to exclude subjects who have temporarily left a stable living arrangement (eg, due to
psychosis). Such subjects remain eligible to participate in this protocol.
Chronically homeless subjects should not be enrolled.

- Subject is in good physical health on the basis of medical history, physical
examination, and laboratory screening.

- Subject who requires concomitant medication treatment with the following agents may
be included if they have been on stable doses (ie, minor adjustments only) for the
specified times: 1) oral hypoglycemics must be stable for at least 30 days prior to
screening, 2) antihypertensive agents must be stable for at least 30 days prior to
screening, and 3) thyroid hormone replacement must be stable for at least 90 days
prior to screening. (Note: CYP3A4 inducers and inhibitors will not be allowed).

- Subject is willing and able to comply with the protocol assessments and visits, in
the opinion of the study nurse/coordinator and the Investigator.

Exclusion Criteria:

Subject has a DSM-IV Axis I or Axis II diagnosis, other than schizophrenia, that has been
the primary focus of treatment within 3 months of screening.

- Subject answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with
some intent to act, without specific plan) or item 5 (active suicidal ideation with
specific plan and intent) on the C-SSRS assessment at screening (ie, in the past one
month) or baseline (ie, since last visit).

- Subject is considered by the Investigator to be at imminent risk of suicide or injury
to self, others, or property.

- Subject has attempted suicide within 3 months prior to the screening phase.

- Subject currently has a clinically significant medical condition including the
following: neurological, metabolic (including Type 1 diabetes), hepatic, renal,
hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological
disorder such as unstable angina, congestive heart failure (uncontrolled), or central
nervous system (CNS) infection that would pose a risk to the subject if they were to
participate in the study or that might confound the results of the study. Subjects
with known human immunodeficiency virus (HIV) seropositivity will be excluded.

Note:Active medical conditions that are minor or well-controlled are not exclusionary if
they do not affect risk to the subject or the study results. In cases in which the impact
of the condition upon risk to the subject or study results is unclear, the Medical Monitor
should be consulted. Any subject with a known cardiovascular disease or condition (even if
controlled) must be discussed with the Medical Monitor during screening.

- Subject has evidence of any chronic organic disease of the CNS such as tumors,
inflammation, and active seizure disorder, vascular disorder, Parkinson's disease,
Alzheimer's disease or other forms of dementia, myasthenia gravis, or other
degenerative processes. In addition, subject must not have a history of mental
retardation or persistent neurological symptoms attributable to serious head injury.
Note: Past history of febrile seizures, drug-induced seizures, or alcohol withdrawal
seizures is not exclusionary.

- Subject demonstrates evidence of acute hepatitis, clinically significant chronic
hepatitis, or evidence of clinically significant impaired hepatic function through
clinical and laboratory evaluation.

Note: Subjects with serum alanine transaminase (ALT) or aspartate transaminase (AST)
levels greater than or equal to 3 times the upper limit of the reference ranges provided
by the central laboratory require retesting. If on retesting the laboratory value remain
greater than or equal to 3 times the upper limit, the subject will be excluded.

- Subject has a history of stomach or intestinal surgery or any other condition that
could interfere with or is judged by the Investigator to interfere with absorption,
distribution, metabolism, or excretion of study drug.

- Subject with Type 1 or Type 2 insulin-dependent diabetes.

- Subject with newly diagnosed Type 2 diabetes during screening. Subject with Type 2
diabetes is eligible for study inclusion if the following condition is met at
screening:

if a subject is currently being treated with oral anti-diabetic medication(s), the dose
must have been stable for at least 4 weeks prior to screening. Such medication may be
adjusted or discontinued during the study, as clinically indicated.

-Subject has any abnormal laboratory parameter at screening that indicates a clinically
significant medical condition as determined by the Investigator. Subjects with a fasting
blood glucose at screening ≥ 126 mg/dL (7.0 mmol/L) or HbA1c ≥ 6.5% will be excluded.

Note: Subjects with random (non-fasting) blood glucose at screening ≥ 200 mg/dL (11.1
mmol/L) must be retested in a fasted state.

- Subject has a prolactin concentration > 100 ng/mL at screening or has a history of
pituitary adenoma.

- Subject has a history of malignancy < 5 years prior to signing the informed consent,
except for adequately treated basal cell or squamous cell skin cancer or in situ
cervical cancer. Pituitary tumors of any duration are excluded.

- Subject is judged to be resistant to antipsychotic treatment defined as any one of
the following:

1. failure to respond to > 2 marketed antipsychotic agents, given at an adequate
dose and for an adequate duration (within the past 2 years)

2. history of treatment with clozapine for refractory psychosis

- Subject is receiving an antipsychotic medication above the maximum recommended
(country-specific) dose at or prior to screening and, in the judgment of the
Investigator, is unlikely to respond to standard doses of lurasidone.

- Subject has received depot antipsychotics unless the last injection was at least one
treatment cycle or at least 30 days (whichever is longer), prior to the screening
phase.

- Subject has received treatment with antidepressants within 7 days (fluoxetine
hydrochloride within 28 days, MAO inhibitors within 14 days) or clozapine within 120
days prior to the double-blind baseline.

- Subject requires treatment with any potent CYP3A4 inhibitors or inducers during the
study (Appendix 3).

- Subject has received electroconvulsive therapy treatment within the 3 months prior to
screening or is expected to require ECT during the study.

- Subject has a history of neuroleptic malignant syndrome.

- Subject exhibits evidence of severe tardive dyskinesia, severe dystonia, or any other
severe movement disorder. Severity will be determined by the Investigator.

- Subject has a history of alcohol or substance abuse (DSM-IV-TR criteria) within 3
months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria)
within 12 months prior to screening. The only exceptions include caffeine or nicotine
abuse/dependence.

- Subject tests positive for drugs of abuse at screening, however, a positive test for
amphetamines, barbiturates, opiates, benzodiazepines or methadone may not result in
exclusion of subjects if the investigator determines that the positive test is as a
result of prescription medicine(s). In the event a subject tests positive for
cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's
ability to abstain from using this substance during the study. This information will
be discussed with the Medical Monitor prior to study enrollment.

- Subject had a history or presence of an abnormal electrocardiogram (ECG), which in
the Investigator's opinion is clinically significant (Medical Monitor may be
consulted to determine clinical significance).

- Subject has poor peripheral venous access that will limit the ability to draw blood
as judged by the Investigator.

- Subject has a history of hypersensitivity to more than 2 distinct chemical classes of
drug (eg, sulfas and penicillins).

- Subject was screened or washed out previously more than three times for this study.

- Subject is currently participating, or has participated in, a study with an
investigational or marketed compound or device within 3 months prior to signing the
informed consent, or has participated in 2 or more studies within 12 months prior to
signing the informed consent.

- Subject is homeless or did not have a stable residence for the 3 months prior to the
screening phase.

- Subject is unable to cooperate with any study procedures, unlikely to adhere to the
study procedures and keep appointments, in the opinion of the Investigator, or was
planning to relocate during the study.

- Subject demonstrates a decrease (improvement) of ≥ 20% in the PANSS total score
between screening and baseline visits (use Appendix 6 for calculation), or the PANSS
total score falls below 80 at baseline.