Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients

Inclusion Criteria:

1. Males or females aged 19 to 65 years inclusive.

2. Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM.5) diagnosis of
Bipolar Type I or Type II Disorder, with or without a history of psychosis. BP II
patients must have had 2 definite periods of hypomania in the last 5 years.

3. All patients must be taking either a mood stabilizer (i.e. lithium or valproate)
(lamotrigine as a mood stabilizer is acceptable for bipolar 2 disorder patients only
and not for bipolar I disorder) or an atypical antipsychotic or a combination of these
(two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), at
therapeutic doses, for mood stabilization. Those taking two atypical antipsychotics
are excluded. Combinations of these medications as outlined above, or the combination
of any of them with lamotrigine 100-400 mg daily, or the combination of a mood
stabilizer plus asenapine 5-20 mg/day, are also permitted.

4. All concomitant medication must be at a stable dose for two weeks prior to the
randomization visit.

5. Clinically stable during the last 4 weeks as assessed by clinical interview.

6. A Montgomery Asberg Depression Rating Scale(MADRS) and Young Mania Rating Scale (YMRS)
score less than or equal to 8.

7. Patients who show cognitive impairments (-0.50 SD or below) on either the Wechsler
Adult Intelligence Scale-IV (WAIS-IV) -Coding subtest, or the Rey Auditory Verbal
Learning Test (RAVLT) total learning score on trials 1 to 5 or immediate recall, at
screening visit.

8. A WAIS-IV vocabulary scaled score >5 (equivalent to estimated IQ 80 or greater).

9. A sufficient level of the English language.

10. Females who are postmenopausal for at least 1 year before the screening visit
(confirmed by an FSH test) or are surgically sterile.

11. Females of childbearing potential who are taking contraceptive pills or agree to
practice effective double barrier methods of contraception, from the time of signing
the informed consent up to the last dose of study drug, and for 7 days after dosing
stops, or who agree to completely abstain from heterosexual intercourse.

12. Capability of understanding, consenting to, and complying with study requirements,
study visits, and to return to the clinic for follow-up evaluations as specified by
the protocol.

Exclusion Criteria:

1. A history of unstable or inadequately treated medical illnesses including moderate to
severe brain injury, or neurological illnesses impacting cognitive function. Patients
with a personal or family history of cardiac problems will need to undergo
Electrocardiogram (EKG) at screen visit, and will be excluded if results are abnormal.

2. Patients taking procognitive medications, clozapine, tricyclic antidepressants,
first-generation antipsychotics, and cogentin.

3. Those taking two or more antipsychotics.

4. Anticholinergics and stimulants that increase dopamine levels are not permitted

5. Cognitive remediation therapy within 3 months prior to entry or during the double
blind phase.

6. Neuromodulation treatment with Electroconvulsive Therapy (ECT) or repetitive
Transcranial Magnetic Stimulation (rTMS) or transcranial Direct Current Stimulation
(tDCS) or Deep Brain Stimulation (DBS) within eight weeks or treatment with an
experimental drug within 30 days.

7. History of nonresponse or intolerance to lurasidone.

8. Psychotic disorder other than Bipolar Disorder.

9. Patients who currently meet criteria for anxiety disorder (General Anxiety Disorder,
Obsessive Compulsive Disorder, Panic disorder, Post Traumatic Stress Disorder).

10. Those with a documented childhood diagnosis of Attention-Deficit/Hyperactivity
Disorder ADHD or other learning disorders.

11. Axis I diagnosis of alcohol/substance abuse or dependence within the past month.

12. Significant risk of harm to self or others.

13. Pregnancy or lactation.

14. Liver function tests three times the upper limit of normal. -