PERSIST: Bipolar Maintenance Study of Lurasidone Adjunctive to Lithium or Divalproex

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01358357
• Collaborator: (none)
• Enrollment: 965
• Locations: 105
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, placebo-controlled, flexible-dose, parallel-group study designed to evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and /or psychotic features.

Condition or Disease	Intervention/Treatment	Phase
Bipolar I Disorder	Drug: Lurasidone; Drug: Placebo	Phase 3

Detailed Description

This study is to evaluate the efficacy and safety of lurasidone (in combination with lithium or divalproex) for the maintenance treatment of bipolar I disorder in subjects with or without rapid cycling and/or psychotic features.

Study Design

• Study Type: Interventional
• Actual Enrollment: 965 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Flexible-dose, Parallel-group Study of Lurasidone Adjunctive to Lithium or Divalproex for the Prevention of Recurrence in Subjects With Bipolar I Disorder
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone 20-80 mg flexible dose	Drug: Lurasidone; Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter
Placebo Comparator: Placebo	Drug: Placebo; 20-80 mg flexible dose

Outcome Measures

Primary Outcome Measures

1. Time to Recurrence of Mood Event During the Double Blind Treatment Phase [28 weeks (up to 33 weeks)]

   A mood event is defined as one of the following during the double-blind phase: (1) Fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) criteria for manic, mixed manic, hypomanic, or depressive episode. (2) Required treatment intervention for manic, mixed manic, hypomanic, or depressive symptoms with any antipsychotic (other than study drug), antidepressant, mood stabilizer (other than lithium or divalproex), anxiolytic agents, benzodiazepine (beyond dosage allowed for anxiety, agitation, or insomnia). (3) Psychiatric hospitalization for any bipolar mood episode. (4) Young Mania Rating Scale (YMRS) or Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 18 or Clinical Global Impression Bipolar Version, Severity of Illness (CGI BP S) score ≥ 4 at 2 consecutive assessments no more than 10 days apart. (5) Discontinuation from the study because of a mood event (as determined by the Investigator).

Secondary Outcome Measures

1. Time to All-cause Discontinuation [28 weeks (up to 33 weeks)]

2. Time to Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode [28 weeks (up to 33 weeks)]

3. Percentage of Subjects Who Experience a Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode [28 weeks]

4. Change From Double-blind Baseline to Week 28 (LOCF) in CGI-BP-S Overall Score [Double-blind Baseline to week 28]

   The CGI-BP-S overall score is a single value, clinician-rated assessment of overall bipolar illness severity and ranges from 1=Normal, not at all ill, to 7=Among the most extremely ill patients. a higher score is associated with greater illness severity.

5. Change From Double -Blind Baseline to Week 28 (LOCF) in CGI-BP-S Mania Score [Double-blind Baseline to week 28]

   The CGI-BP-S mania score is a single value, clinician-rated assessment of mania illness severity and ranges from 1=Normal, not at all ill to 7=Among the most extremely ill patients. A high score is associated with greater illness severity

6. Change From Double-blind Baseline to Week 28 (LOCF) in CGI+-BP-S Depression Score [Double-blind Baseline to week 28]

   The CGI-BP-S depression score is a single value, clinician-rated assessment of depression illness severity and ranges from 1=Normal, not at all ill to 7=Among the most extremely ill patients. A higher score is associated with a greater illness severity.

7. Change From Double-blind Baseline to Week 28 (LOCF) in YMRS Total Score [Double-blind Baseline to week 28]

   the YMRS is an 11-item instrument used to assess the severity of mania in subjects with a diagnosis of bipolar disorder. Ratings are based on patient self-reporting, combined with clinician observation (accorded greater score). The YMRS total score is calculated as the sum of the 11 items. The YMRS total score ranges from 0 to 60. Higher scores are associated with greater severity of maia.

8. Change From Double-blind Baseline to Week 28 (LOCF) in MADRS Total Score [Double-blind Baseline to week 28]

   The MADRS consists of 10 items, each rated on a Likert scale, from 0=Normal to 6=Most Severe. The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity of depressive symptoms.

9. Change Fro Double-blind Baseline to Week 28 (LOCF) in QIDS-SR(16) Total Score [Double-blind Baseline to week 28]

   The QIDS-SR16 is a 16-item self-report measure of depressive symptomatology which uses a computerized assessment interface for administration. The scoring system for the QIDS-SR16 converts responses to 16 separate items into nine DSM-IV symptom criterion domains. The nine domains comprise: depressed mood (Item 5); concentration/decision making (Item 10); self outlook (Item 11); suicidal ideation (Item 12); decreased interest (Item 13); decreased energy (Item 14); sleep disturbance (initial, middle, and late insomnia or hypersomnia) (highest score of Items 1 to 4); appetite/weight disturbance (highest score of Items 6 to 9); and psychomotor disturbance (highest score of Items 15 and 16). The QIDS-SR16 total score is calculated as the sum of the 9 domain scores. The QIDS-SR16 total score ranges from 0 to 27 with a high score indicating more severe symptoms.

10. Change From Double-blind Baseline to Week 28 (LOF) in PANSS Positive Symptom (PANNS-P) Subscale Score [Double-blind Baseline to week 28]

    The PANSS-P is a subset of items in the PANSS, an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS-P subscale score is the sum of the 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity.

11. Change From Double-blind Baseline to Week 28 (LOCF) in SDS Total Score [Double-blind Baseline to week 28]

    The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by depressive symptoms. The SDS total score is calculated as the sum of the 3 items. The SDS total score ranges from 0 to 30. Higher scores are associated with greater severity of global functional impairments. If a subject has not worked/studied at all during the past week for reasons unrelated to the disorder, the SDS total score will be set to missing.

12. Change From Double-blind Baseline to Week 28 (LOCF) in PIRS-2 Total Score [Double-blind Baseline to week 28]

    The PIRS-2 is a 2-item self-report of insomnia assessed via a computer interface. Each item is scored from 0-3. The PIRS-2 total score is calculated as the sum of the 2 items. The PIRS total score ranges from 0 to 6. Higher scores are associated with greater severity of insomnia.

13. Change From Double-blind Baseline to Week 28 (LOCF) in Q-LES-Q-SF Percent Maximum Possible Score [Double-blind Baseline to week 28]

    The Q-LES-Q-SF is a 16-item self-report measure of the degree of enjoyment and satisfaction in various areas of daily living. The questionnaire was developed and validated for use in depressed outpatient subjects and has eight summary scales that reflect major areas of functioning: physical health, mood, leisure time activities, social relationships, general activities, work, household duties and school/coursework. Each item is rated on a 5-point scale, ranging from 1 (very poor) to 5 (very good). The Q-LES-Q-SF percentage maximum possible score is calculated as 100 × (Raw Score - 14 [Minimum Score]) / (70 [Maximum Score] - 14 [Minimum Score]). Higher percent maximum scores indicate better quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Open-label Phase

• 18 years of age or older

• Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I disorder

•≥ 1 manic, mixed manic, or depressed episode in past 2 years

• YMRS or MADRS total score ≥ 14 if on lithium or divalproex; ≥ 18 if not on lithium or divalproex

Double-blind Phase

Inclusion Criteria:

• Subjects must achieve consistent clinical stability, defined as total scores ≤ 12 on the YMRS and MADRS over at least 12 weeks, with the allowance of two excursions (YMRS and/or MADRS total scores up to 13 or 14, respectively) except during the last 4 weeks before randomization

Exclusion Criteria:

Open Label Phase

• Diagnosis of an Axis I or Axis II disorder, other than bipolar I disorder, that is the primary focus of treatment within 3 months of screening

• Subjects for whom diagnostic agreement between the Investigator and United BioSource Corporation (Boston) (UBC) cannot be reached

• Ultra-fast rapid cycling (defined as ≥ 8 mood episodes over the previous 12-month period)

• Subjects who test positive for drugs of abuse at screening. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's ability to abstain from cannabis during the study

• Unstable/inadequately treated medical illness

• The subjects answers "yes" to "Suicidal Ideation" items 4 or 5 on the C-SSRS (at time of evaluation)

Double Blind Phase

• Subjects who in the Investigator's judgment have not been compliant with study medication during the stabilization phase

• Subjects who have not stabilized during the open-label phase (within 20 weeks)

• Subjects who test positive for drugs of abuse at double-blind phase baseline. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the Investigator will evaluate the subject's ability to abstain from cannabis during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Harmonex Neuroscience Research	Dothan	Alabama	United States	36303
2	Behavioral Research Specialists, LLC	Glendale	California	United States	91206
3	AXIS Clinical Trials	Los Angeles	California	United States	90036
4	Excell Research, Inc.	Oceanside	California	United States	92056
5	Stanford University School of Medicine Research Program VA Palo Alto Health Care System	Palo Alto	California	United States	94304
6	SF-CARE, Inc.	San Francisco	California	United States	94117
7	Neuropsychiatric Research Center of Orange County	Santa Ana	California	United States	92701
8	"Stanford University School of Medicine	Stanford	California	United States	94305
9	Florida Clinical Research LLC	Bradenton	Florida	United States	34201
10	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32216
11	Galiz Research	Miami Springs	Florida	United States	33166
12	Clinical Neuroscience Solutions	Orlando	Florida	United States	32806
13	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30308
14	Clinco	Terre Haute	Indiana	United States	47802
15	ActivMed Practices & Research Inc.	Haverhill	Massachusetts	United States	08130
16	Psych Care Consultants Research	St. Louis	Missouri	United States	63128
17	Village Clinical Research Inc,	New York	New York	United States	10003
18	Finger Lakes Clinical Research	Rochester	New York	United States	14618
19	Charak Center for Health and Wellness	Garfield Heights	Ohio	United States	44125
20	Cutting Edge Research Groupd	Oklahoma City	Oklahoma	United States	73116
21	Suburban Research Associates	Media	Pennsylvania	United States	19063
22	Lincoln Research	Lincoln	Rhode Island	United States	02865
23	Carolina Clinical Trials, Inc.	Charleston	South Carolina	United States	29407
24	Clinical Neuroscience Solutions Inc.	Memphis	Tennessee	United States	38119
25	Psychoneuroendocrinology Research Group, Dept of Psychiatry, UT Southwestern Medical Center	Dallas	Texas	United States	75235
26	R/D Clinical Research, Inc.	Lake Jackson	Texas	United States	77566
27	Sanatorio Morra	Cordoba	Provincia de Cordoba	Argentina	5009
28	Centro de Atencion E Invest. Clinica (CAICI)	Rosario	Santa Fe	Argentina	2000
29	Novain Neurociencias Group	Buenos Aires		Argentina	C1117ABH
30	Centro de Neuropsiquiatria	Buenos Aires		Argentina	C1425AHQ
31	IPEM-Instituto de Prevención de las Enfermedades Mentales.	Buenos Aires		Argentina
32	Instituto DAMCI	Cordoba		Argentina	5009
33	Clinica Privada de Salud Mental Santa Teresa de Avila	La Plata		Argentina	1900
34	Centro de Psiquiatria Biologica	Mendoza		Argentina	5500
35	The Lyell McEwin Hospital	Elizabeth Vale	South Australia	Australia	5112
36	RWF Medic Pty Ltd as Trustee for Farnbach Family Trust at Neurotherapy Victoria	Malvern	Victoria	Australia	3144
37	The Melbourne Clinic	Richmond	Victoria	Australia	3121
38	Hollywood Medical Centre	Fremantle	Western Australia	Australia	6160
39	Psychiatry Dispensary	Bourgas		Bulgaria	80000
40	University Multiprofiled Hospital for Active Treatment "Sveti Georgi"	Plovdiv		Bulgaria	4002
41	Regional Psychiatric Dispensary	Rousse		Bulgaria	7003
42	Multiprofiled Hospital for Active Treatment "Alexandrovska"	Sofia		Bulgaria	1431
43	Psychiatric Clinic, Military Medical Academy	Sofia		Bulgaria	1606
44	Multprofiled Hospital for Active Treatment "Sveta Marina"	Varna		Bulgaria	9010
45	CETEP	Santiago		Chile	27014
46	Clinica Las Condes	Santiago		Chile	27014
47	Psicomedica	Santiago		Chile	27014
48	Clinic Hospital Centre Rijeka Clinic for Psychiatry	Rijeka		Croatia	51000
49	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
50	Klinicki Bolnicki Centar Zagreb-Rebro	Zagreb		Croatia	10000
51	University Hospital Sestremilosrdnice	Zagreb		Croatia
52	University Hospital Centre Zagreb	Zagreg		Croatia	10000
53	Fakultni Nemocnice Brno	Brno-Bohunice		Czech Republic	62500
54	Saint Anne s.r.o.	Brno		Czech Republic	602 00
55	Psychiatricka ambulance	Havirov		Czech Republic	736 01
56	Psychiatricka Iecebna U Honzicka	Pisek		Czech Republic	397 01
57	Psychiatricke Centrum Praha	Prague 8-Bohunice		Czech Republic	62500
58	Psychiatricka Ambulance	Prague		Czech Republic	10600
59	Clintrial s.r.o.	Praha 10		Czech Republic	100 00
60	Psychiatricka ambulance Prosek	Praha 3		Czech Republic	190 00
61	Psychiaricka ambulance	Praha 4		Czech Republic	140 00
62	Psychosocialni Centrum	Prerov		Czech Republic	75001
63	Psychiatricka ambulance	Usti nad labem		Czech Republic	401 13
64	CHS La Chartreuse-Pole 6	Dijon cedex		France	21033
65	Centre Hospitalier Specialise du Jura-Centre Medico Psychiatrique	Dole		France	39100
66	Hopital Lapeyronie	Montpellier Cedex 5		France	34295
67	CHRU de Nimes, Service de Psychiatrie adulte	Nimes Cedex 09		France	30029
68	Obudai Egeszsegugyi Centurm Kft.	Budapest		Hungary	1036
69	Fovarosi Onkormanyzat Szent Istvan Korhaz es Szent Laszlo Korhaz	Budapest		Hungary	1096
70	Kutvolgyi Klinikai Tomb SOTE IIIsz Belgyogyaszati Klinika	Budapest		Hungary	1125
71	Nyiro Gyula Korhaz	Budapest		Hungary	1135
72	Fovarosi Onkormanyzat Nyiro Gyula Korhaz, I. Pszichiatria	Budapest		Hungary	H-1135
73	Petz Aladar Megyei Oktato Korhaz	Gyor		Hungary	9024
74	Bekes Megyei Kepviselotestulet Pandy Kalman Korhaz	Gyula		Hungary	5700
75	Haruna Hospital	Shibukawa	Gunma	Japan
76	Goryokai Medical Corporation	Sapporo-shi	Hokkaido	Japan	002-8029
77	Sapporokousetsu Hospital	Sapporo	Hokkaido	Japan
78	Nagano Prefectural Mental Wellness Center-Komagane	Komagane,	Nagano	Japan
79	Shonan Hospital	Matsumoto-shi	Nagano	Japan	390-0847
80	Asakayama General Hospital	Sakai	Osaka	Japan
81	National Hospital Organization Hizen Psychiatric Center	Kanzaki	Saga	Japan	842-0192
82	Nishigahara Hospital	Kita-ku	Tokyo	Japan	114-0024
83	Okehazama Hospital Fujita Kokoro Care Center	Aichi		Japan	470-1168
84	Ongata Hospital	Hachioji, Tokyo		Japan
85	Yuge Hospital	Kumamoto		Japan	861-8002
86	Arakaki Hospital	Okinawa		Japan	904-0012
87	Kawada Hospital	Toyama		Japan	933-0917
88	NZOZ Syntonia	Gdynia		Poland	81-361
89	NZOZ BioMed	Kielce		Poland	25411
90	Wojewodzki Osrodek Lexznictwa Psychiatrycznego w Toruniu	Torun		Poland	87-100
91	Prywatny Gabinet Lekarski Jaroslaw Strzelec	Tuszyn		Poland	95-080
92	Przychodnia Lekarsko-Psychologiczna "Persona" Spolka Partnerska Lekarzy	Wroclaw		Poland	50-227
93	State Healthcare and Forensic Psychiatric Expertise Institution	Izhevsk		Russian Federation	462054
94	Nizhny Novgorod Regional State Institution of Healthcare	Nizhniy Novgorod		Russian Federation	603155
95	St. Petersburg State Healthcare Institution (SPSHI)	St. Petersburg		Russian Federation	190005
96	St.Petersburg State Healthcare Institution (SPSHI)	St. Petersburg		Russian Federation	190005
97	St Petersburg State Government Healthcare Institution	St. Petersburg		Russian Federation	190121
98	Mental Health Research Institute of Rams	Tomsk		Russian Federation	634050
99	Clinical Centre of Serbia	Belgrade		Serbia	11000
100	Clinical Hospital Centre Dragisa Misovic	Belgrade		Serbia	11000
101	Psychiatric Clinic Clinical Center Kragujevac	Kragujevac		Serbia	34000
102	Clinical Centre Nis	Nis		Serbia	18000
103	Specialized Hospital for Psychiatric Diseased "Sveti Vracevi"	Novi Knezevac		Serbia	23330
104	Vseobecna Nemocnica Rimavska Sobota, NaP, n.o. Bratislava	Rimavska Sobota		Slovakia	97912
105	Psychiatricka ambulancia	Zlate Moravce		Slovakia	95301

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Medical Director, MD, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT01358357
• Other Study ID Numbers: D1050296; 2011-000986-10
• First Posted: May 23, 2011
• Last Update Posted: Sep 7, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Sunovion: Lurasidone; Latuda; Bipolar I
• Additional relevant MeSH terms: Lurasidone Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	There were 2 phases in this study. In Phase 1 (Open-label Stabilization Phase), there was 1 reporting group. In phase 2 (Double-blind Maintenance Phase), there were 2 reporting groups. 7 subjects completed the open-label but were not randomized DB(3- mood episode,3-not meeting the criteria for the DB phase,and 1-insufficient clinical response)

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo	All Subjects
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose	During the Open-label stabilization phase, subjects received flexible does of lurasidone 20 - 80 mg daily.
Period Title: Open Label Phase
STARTED	0	0	965
COMPLETED	0	0	503
NOT COMPLETED	0	0	462
Period Title: Open Label Phase
STARTED	246	250	0
COMPLETED	166	150	0
NOT COMPLETED	80	100	0

Baseline Characteristics

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo	Total
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose	Total of all reporting groups
Overall Participants	246	250	496
Age (Count of Participants)
<=18 years	2 0.8%	0 0%	2 0.4%
Between 18 and 65 years	232 94.3%	242 96.8%	474 95.6%
>=65 years	12 4.9%	8 3.2%	20 4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (12.43)	43.2 (12.18)	44.4 (12.36)
Sex: Female, Male (Count of Participants)
Female	136 55.3%	143 57.2%	279 56.3%
Male	110 44.7%	107 42.8%	217 43.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	41 16.7%	38 15.2%	79 15.9%
Not Hispanic or Latino	205 83.3%	212 84.8%	417 84.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 0.8%	2 0.4%
Asian	6 2.4%	7 2.8%	13 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	23 9.3%	21 8.4%	44 8.9%
White	213 86.6%	216 86.4%	429 86.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 1.6%	4 1.6%	8 1.6%
Region of Enrollment (participants) [Number]
Argentina	19 7.7%	19 7.6%	38 7.7%
Russian Federation	30 12.2%	31 12.4%	61 12.3%
Hungary	13 5.3%	15 6%	28 5.6%
United States	73 29.7%	76 30.4%	149 30%
Japan	5 2%	5 2%	10 2%
Czech Republic	23 9.3%	24 9.6%	47 9.5%
Poland	22 8.9%	21 8.4%	43 8.7%
Slovakia	4 1.6%	3 1.2%	7 1.4%
Bulgaria	20 8.1%	20 8%	40 8.1%
Chile	9 3.7%	11 4.4%	20 4%
France	8 3.3%	6 2.4%	14 2.8%
Serbia	20 8.1%	19 7.6%	39 7.9%

Outcome Measures

1. Primary Outcome

Title	Time to Recurrence of Mood Event During the Double Blind Treatment Phase
Description	A mood event is defined as one of the following during the double-blind phase: (1) Fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th Ed., Text Revision (DSM-IV-TR) criteria for manic, mixed manic, hypomanic, or depressive episode. (2) Required treatment intervention for manic, mixed manic, hypomanic, or depressive symptoms with any antipsychotic (other than study drug), antidepressant, mood stabilizer (other than lithium or divalproex), anxiolytic agents, benzodiazepine (beyond dosage allowed for anxiety, agitation, or insomnia). (3) Psychiatric hospitalization for any bipolar mood episode. (4) Young Mania Rating Scale (YMRS) or Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 18 or Clinical Global Impression Bipolar Version, Severity of Illness (CGI BP S) score ≥ 4 at 2 consecutive assessments no more than 10 days apart. (5) Discontinuation from the study because of a mood event (as determined by the Investigator).
Time Frame	28 weeks (up to 33 weeks)

Outcome Measure Data

Analysis Population Description

ITT (Intent to treat) population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	246	250
Median (95% Confidence Interval) [Days]	NA	207

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments	It was assumed that the recurrence event rates during the double-blind phase were to be 24% and 39% for subjects treated with lurasidone and placebo, respectively. A total of 120 recurrence events were required to achieve 90% power to detect the 15% difference in subjects who had a recurrence event during the double-blind phase between the treatment groups using a log-rank test with two sided alpha level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.078
	Comments	A hazard ratio of time to recurrence and its corresponding 95% Wald CI were estimated for the lurasidone arm vs.placebo arm, using a Cox proportional hazards model.Cox model included treatment effect as fixed effect, and stratified by pooled country.
	Method	Cox Proportional Hazards Model
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to All-cause Discontinuation
Time Frame	28 weeks (up to 33 weeks)

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	246	250
Median (95% Confidence Interval) [Days]	225	207

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.034
	Comments	A HR of time to discontinuation and corresponding 95% Wald CI were est. for lurasidone arm vs.the placebo arm, using a Cox proportional hazards model. Model included treatment effect including treatment as a fixed effect,stratified by pooled country.
	Method	Cox Proportional Hazards Model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode
Time Frame	28 weeks (up to 33 weeks)

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	246	250
Median (95% Confidence Interval) [Days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.113
	Comments	A HR of time to recurrence and its corresponding 95% Wald CI were estimated for lurasidone arm vs. placebo arm,using a Cox proportional hazards model. Model included treatment effect including treatment as a fixed effect stratified by pooled country.
	Method	Cox Proportional hazard Model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Subjects Who Experience a Recurrence of a Manic, Mixed Manic, Hypomanic, or Depressed Episode
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	246	250
Number [percentage of participants]	16.7 6.8%	21.6 8.6%

5. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in CGI-BP-S Overall Score
Description	The CGI-BP-S overall score is a single value, clinician-rated assessment of overall bipolar illness severity and ranges from 1=Normal, not at all ill, to 7=Among the most extremely ill patients. a higher score is associated with greater illness severity.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. 2 lurasidone + Li/VPA subjects did not have post-DB baseline CGI-BP-S overall score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	244	250
Least Squares Mean (Standard Error) [units on a scale]	0.40 (0.085)	0.49 (0.085)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.406
	Comments	analysis of ANCOVA model contains treatment ,pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Double -Blind Baseline to Week 28 (LOCF) in CGI-BP-S Mania Score
Description	The CGI-BP-S mania score is a single value, clinician-rated assessment of mania illness severity and ranges from 1=Normal, not at all ill to 7=Among the most extremely ill patients. A high score is associated with greater illness severity
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. . 2 lurasidone + Li/VPA subjects did not have post-DB baseline CGI-BP-S mania score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	244	250
Least Squares Mean (Standard Error) [units on a scale]	0.10 (0.062)	0.21 (0.062)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.162
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in CGI+-BP-S Depression Score
Description	The CGI-BP-S depression score is a single value, clinician-rated assessment of depression illness severity and ranges from 1=Normal, not at all ill to 7=Among the most extremely ill patients. A higher score is associated with a greater illness severity.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. 2 lurasidone + Li/VPA subjects did not have post-DB baseline CGI-BP-S depression score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	244	250
Least Squares Mean (Standard Error) [units on a scale]	0.35 (0.082)	0.42 (0.081)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.496
	Comments	Analysis of covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in YMRS Total Score
Description	the YMRS is an 11-item instrument used to assess the severity of mania in subjects with a diagnosis of bipolar disorder. Ratings are based on patient self-reporting, combined with clinician observation (accorded greater score). The YMRS total score is calculated as the sum of the 11 items. The YMRS total score ranges from 0 to 60. Higher scores are associated with greater severity of maia.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. . 2 lurasidone + Li/VPA subjects did not have post-DB baseline YMRS total score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	244	250
Least Squares Mean (Standard Error) [units on a scale]	1.0 (0.43)	1.8 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.128
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pool country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.8 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in MADRS Total Score
Description	The MADRS consists of 10 items, each rated on a Likert scale, from 0=Normal to 6=Most Severe. The MADRS total score is calculated as the sum of the 10 items. The MADRS total score ranges from 0 to 60. Higher scores are associated with greater severity of depressive symptoms.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. 2 lurasidone + Li/VPA subjects did not have post-DB baseline MADRS total score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	244	250
Least Squares Mean (Standard Error) [units on a scale]	3.0 (0.57)	3.5 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.485
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasdione vs.Placebo
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change Fro Double-blind Baseline to Week 28 (LOCF) in QIDS-SR(16) Total Score
Description	The QIDS-SR16 is a 16-item self-report measure of depressive symptomatology which uses a computerized assessment interface for administration. The scoring system for the QIDS-SR16 converts responses to 16 separate items into nine DSM-IV symptom criterion domains. The nine domains comprise: depressed mood (Item 5); concentration/decision making (Item 10); self outlook (Item 11); suicidal ideation (Item 12); decreased interest (Item 13); decreased energy (Item 14); sleep disturbance (initial, middle, and late insomnia or hypersomnia) (highest score of Items 1 to 4); appetite/weight disturbance (highest score of Items 6 to 9); and psychomotor disturbance (highest score of Items 15 and 16). The QIDS-SR16 total score is calculated as the sum of the 9 domain scores. The QIDS-SR16 total score ranges from 0 to 27 with a high score indicating more severe symptoms.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. 7 lurasidone + Li/VPA subjects and 7 placebo +Li/VPA subjects did not have post-DB baseline QIDS-SR16 total score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	239	243
Least Squares Mean (Standard Error) [units on a scale]	0.9 (0.27)	1.1 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.582
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.8 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOF) in PANSS Positive Symptom (PANNS-P) Subscale Score
Description	The PANSS-P is a subset of items in the PANSS, an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. An anchored Likert scale from 1-7, where values of 2 and above indicate the presence of progressively more severe symptoms, is used to score each item. The PANSS-P subscale score is the sum of the 7 items and ranges from 7 through 49. A higher score is associated with greater illness severity.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT Population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. . 6 lurasidone + Li/VPA subjects and 3 placebo +Li/VPA subjects did not have post-DB baseline PANSS-P score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	240	247
Least Squares Mean (Standard Error) [units on a scale]	0.2 (0.13)	0.3 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.420
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in SDS Total Score
Description	The SDS is a composite of three self-rated items designed to measure the extent to which three major sectors in the patient's life are impaired by depressive symptoms. The SDS total score is calculated as the sum of the 3 items. The SDS total score ranges from 0 to 30. Higher scores are associated with greater severity of global functional impairments. If a subject has not worked/studied at all during the past week for reasons unrelated to the disorder, the SDS total score will be set to missing.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT Population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on treatment they were randomized. 63 lurasidone + Li/VPA subjects and 57 placebo +Li/VPA subjects did not have post-DB baseline SDS total score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	183	193
Least Squares Mean (Standard Error) [units on a scale]	0.4 (0.59)	0.6 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.788
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in PIRS-2 Total Score
Description	The PIRS-2 is a 2-item self-report of insomnia assessed via a computer interface. Each item is scored from 0-3. The PIRS-2 total score is calculated as the sum of the 2 items. The PIRS total score ranges from 0 to 6. Higher scores are associated with greater severity of insomnia.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT Population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. . 7 lurasidone + Li/VPA subjects and 7 placebo +Li/VPA subjects did not have post-DB baseline PIRS-2 total score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	239	243
Least Squares Mean (Standard Error) [units on a scale]	0.4 (0.10)	0.5 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.380
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Double-blind Baseline to Week 28 (LOCF) in Q-LES-Q-SF Percent Maximum Possible Score
Description	The Q-LES-Q-SF is a 16-item self-report measure of the degree of enjoyment and satisfaction in various areas of daily living. The questionnaire was developed and validated for use in depressed outpatient subjects and has eight summary scales that reflect major areas of functioning: physical health, mood, leisure time activities, social relationships, general activities, work, household duties and school/coursework. Each item is rated on a 5-point scale, ranging from 1 (very poor) to 5 (very good). The Q-LES-Q-SF percentage maximum possible score is calculated as 100 × (Raw Score - 14 [Minimum Score]) / (70 [Maximum Score] - 14 [Minimum Score]). Higher percent maximum scores indicate better quality of life.
Time Frame	Double-blind Baseline to week 28

Outcome Measure Data

Analysis Population Description

ITT Population: all subjects who were randomized and received at least one dose of study medication in the double-blind phase. Subjects were analyzed based on the treatment they were randomized. . 12 lurasidone + Li/VPA subjects and 11 placebo +Li/VPA subjects did not have post-DB baseline Q-LES-Q-SF percent maximum possible score.

Arm/Group Title	Lurasidone 20-80 mg Flexible Dose	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter	Placebo: 20-80 mg flexible dose
Measure Participants	234	239
Least Squares Mean (Standard Error) [units on a scale]	-1.70 (1.022)	-2.07 (1.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20-80 mg Flexible Dose, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.772
	Comments	Analysis of Covariance (ANCOVA) model contains treatment, and pooled country, and mood stabilizer (lithium or divalproex) as fixed factors and baseline as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS mean difference lurasidone vs.Placebo
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; -2.14 to 2.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	For all subjects column: during open label phase (up to 20 weeks) For 7 lurasidone + Li/VPA and placebo +Li/VPA columns: during double blind phase (up to 28 weeks).
Adverse Event Reporting Description	During the open label phase there were 965 subjects There were three subjects that never received study drug and therefore are not included in this section
Arm/Group Title	Lurasidone 20-80 mg Flexible Dose		Placebo		All Subjects
Arm/Group Description	Lurasidone: Lurasidone 20 mg daily (days 1-3), Lurasidone 40 mg daily (days 4-7), Lurasidone 20-80 mg daily (flexible dose) thereafter		Placebo: 20-80 mg flexible dose		During the open-label stabilization phase, subjects received flexible does of lurasidone 20-80 mg daily
All Cause Mortality
	Lurasidone 20-80 mg Flexible Dose		Placebo		All Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lurasidone 20-80 mg Flexible Dose		Placebo		All Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/246 (5.3%)		11/250 (4.4%)		41/962 (4.3%)
Cardiac disorders
Artiral fibrillation	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Gastrointestinal disorders
Adominal pain	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
General disorders
Chest discomfort	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Hepatobiliary disorders
Cholelithiasis	1/246 (0.4%)	1	1/250 (0.4%)	1	0/962 (0%)	0
Cholecytitis acute	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Cholecystitis chronic	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Infections and infestations
Appendicitis	1/246 (0.4%)	1	0/250 (0%)	0	0/962 (0%)	0
Gastroenteritis	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Postoperative Wound Infection	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Injury, poisoning and procedural complications
Ankle Fracture	0/246 (0%)	0	0/250 (0%)	0	2/962 (0.2%)	2
Clavicle Fracture	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Facial Bones Fracture	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	2
Lower Limb Fracture	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Toxicity to Various Agents	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Investigations
Alanine Aminotransferase Increased	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Aspartate Aminotransferase Increased	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	1/246 (0.4%)	1	0/250 (0%)	0	0/962 (0%)	0
Type 2 Diabetes Mellitus	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Chondromalacia	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Patellofemoral Pain Syndrome	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Joint Swelling	1/246 (0.4%)	1	0/250 (0%)	0	0/962 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign Ovarian Tumour	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Brain Neoplasm	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Ovarian Cancer	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Nervous system disorders
Convulsion	0/246 (0%)	0	1/250 (0.4%)	1	1/962 (0.1%)	1
Headache	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Cerebral edema	0/246 (0%)	0	1/250 (0.4%)	1	1/962 (0.1%)	1
Psychiatric disorders
Depression	2/246 (0.8%)	2	1/250 (0.4%)	1	10/962 (1%)	10
Mania	2/246 (0.8%)	2	3/250 (1.2%)	3	5/962 (0.5%)	5
Agitation	0/246 (0%)	0	0/250 (0%)	0	2/962 (0.2%)	2
Suicidal Ideation	2/246 (0.8%)	2	0/250 (0%)	0	2/962 (0.2%)	2
Bipolar 1 Disorder	1/246 (0.4%)	1	2/250 (0.8%)	2	2/962 (0.2%)	2
Bipolar Disorder	1/246 (0.4%)	1	0/250 (0%)	0	0/962 (0%)	0
Intentional Self Injury	1/246 (0.4%)	1	0/250 (0%)	0	0/962 (0%)	0
Suicide Attempt	1/246 (0.4%)	1	0/250 (0%)	0	2/962 (0.2%)	2
Depressive Symptom	0/246 (0%)	0	0/250 (0%)	0	2/962 (0.2%)	2
Acute Psychosis	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Anxiety	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Insomnia	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Panic Attack	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Somatoform Disorder	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Renal and urinary disorders
Nephrolithiasis	1/246 (0.4%)	1	0/250 (0%)	0	0/962 (0%)	0
Reproductive system and breast disorders
Ovarian Cyst	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Uterine Prolapse	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/246 (0%)	0	0/250 (0%)	0	1/962 (0.1%)	1
Vascular disorders
Hypotension	0/246 (0%)	0	1/250 (0.4%)	1	0/962 (0%)	0
Other (Not Including Serious) Adverse Events
	Lurasidone 20-80 mg Flexible Dose		Placebo		All Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/246 (32.9%)		81/250 (32.4%)		474/962 (49.3%)
Gastrointestinal disorders
Nausea	0/246 (0%)	0	0/250 (0%)	0	111/962 (11.5%)	126
Vomiting	0/246 (0%)	0	0/250 (0%)	0	59/962 (6.1%)	66
Diarrhoea	0/246 (0%)	0	0/250 (0%)	0	53/962 (5.5%)	56
Fatigue	0/246 (0%)	0	0/250 (0%)	0	29/962 (3%)	30
Infections and infestations
Nasopharyngitis	15/246 (6.1%)	17	12/250 (4.8%)	12	39/962 (4.1%)	45
Upper Respiratory Tract Infection	2/246 (0.8%)	2	9/250 (3.6%)	9	0/962 (0%)	0
Investigations
Weight Increased	24/246 (9.8%)	24	13/250 (5.2%)	15	0/962 (0%)	0
Metabolism and nutrition disorders
Increased Appetite	0/246 (0%)	0	0/250 (0%)	0	30/962 (3.1%)	30
Nervous system disorders
Headache	21/246 (8.5%)	25	17/250 (6.8%)	21	88/962 (9.1%)	114
Tremor	15/246 (6.1%)	16	11/250 (4.4%)	12	43/962 (4.5%)	48
Somnolence	0/246 (0%)	0	4/250 (1.6%)	4	69/962 (7.2%)	75
Sedation	0/246 (0%)	0	0/250 (0%)	0	34/962 (3.5%)	44
Akathisia	9/246 (3.7%)	10	8/250 (3.2%)	12	80/962 (8.3%)	91
Psychiatric disorders
Insomnia	9/246 (3.7%)	10	16/250 (6.4%)	25	77/962 (8%)	108
Anxiety	4/246 (1.6%)	7	11/250 (4.4%)	17	41/962 (4.3%)	54

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In the event the Study is part of a multi-center study, the first publication of the results of the study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.