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) diagnosisof Bipolar Type I or Type II Disorder, with or without a history of psychosis. BP IIpatients 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 onlyand not for bipolar I disorder) or an atypical antipsychotic or a combination ofthese (two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), attherapeutic doses, for mood stabilization. Those taking two atypical antipsychoticsare excluded. Combinations of these medications as outlined above, or thecombination of any of them with lamotrigine 100-400 mg daily, or the combination ofa 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 therandomization 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 WechslerAdult Intelligence Scale-IV (WAIS-IV) -Coding subtest, or the Rey Auditory VerbalLearning Test (RAVLT) total learning score on trials 1 to 5 or immediate recall, atscreening visit.

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

9. A sufficient level of the English or Japanese 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 topractice effective double barrier methods of contraception, from the time of signingthe informed consent up to the last dose of study drug, and for 7 days after dosingstops, 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 bythe protocol.

Exclusion Criteria:

1. A history of unstable or inadequately treated medical illnesses including moderateto severe brain injury, or neurological illnesses impacting cognitive function.Patients with a personal or family history of cardiac problems will need to undergoEKG 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. Those taking strong CYP3A4 inhibitors (e.g. clarithromycin, nefazodone, grapefruitjuice) or strong CYP3A4 inducers (e.g. carbamazepine, St John's wort (Hypericumperforatum). Please refer to the current Lurasidone SmPC for further listedcontraindications.

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

6. Cognitive remediation therapy within 3 months prior to entry or during the doubleblind phase.

7. Neuromodulation treatment with ECT or rTMS or tDCS or DBS within eight weeks ortreatment with an experimental drug within 30 days.

8. History of nonresponse or intolerance to lurasidone.

9. Psychotic disorder other than Bipolar Disorder.

10. Patients who currently meet criteria for anxiety disorder (GAD, OCD, Panic disorder,PTSD).

11. Those with a current or lifetime diagnosis of ADHD or other learning disorders.

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

13. Significant risk of harm to self or others.

14. Pregnancy or lactation.

15. Liver function tests (AST and ALT) three times the upper limit of normal.