Trial Outcomes & Findings for PEARL Schizophrenia Maintenance (NCT NCT01435928)

NCT ID: NCT01435928

Last Updated: 2016-04-08

Results Overview

The Kaplan-Meier method is used for the estimation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

676 participants

Primary outcome timeframe

Double-blind phase - 28 Weeks

Results posted on

2016-04-08

Participant Flow

Participant milestones

Participant milestones
Measure	All Subjects During the Open Label Phase subjects will receive Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Lurasidone During double blind phase subjects received Lurasidone flexibly dosed 40 or 80 mg once daily	Placebo During double blind phase subjects received matching placebo.
Open Label Phase - up to 24 Weeks STARTED	676	0	0
Open Label Phase - up to 24 Weeks COMPLETED	287	0	0
Open Label Phase - up to 24 Weeks NOT COMPLETED	389	0	0
Double Blind Phase - 28 Weeks STARTED	0	144	141
Double Blind Phase - 28 Weeks COMPLETED	0	28	20
Double Blind Phase - 28 Weeks NOT COMPLETED	0	116	121

Reasons for withdrawal

Reasons for withdrawal
Measure	All Subjects During the Open Label Phase subjects will receive Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Lurasidone During double blind phase subjects received Lurasidone flexibly dosed 40 or 80 mg once daily	Placebo During double blind phase subjects received matching placebo.
Open Label Phase - up to 24 Weeks Adverse Event	83	0	0
Open Label Phase - up to 24 Weeks Death	1	0	0
Open Label Phase - up to 24 Weeks Lack of Efficacy	46	0	0
Open Label Phase - up to 24 Weeks Lost to Follow-up	60	0	0
Open Label Phase - up to 24 Weeks Protocol Violation	39	0	0
Open Label Phase - up to 24 Weeks Withdrawal by Subject	96	0	0
Open Label Phase - up to 24 Weeks did not meet stabilization criteria	44	0	0
Open Label Phase - up to 24 Weeks Terminated at study completion	6	0	0
Open Label Phase - up to 24 Weeks Administrative	14	0	0
Double Blind Phase - 28 Weeks Adverse Event	0	3	1
Double Blind Phase - 28 Weeks Lost to Follow-up	0	2	5
Double Blind Phase - 28 Weeks Protocol Violation	0	11	4
Double Blind Phase - 28 Weeks Withdrawal by Subject	0	5	12
Double Blind Phase - 28 Weeks Terminated at study completion	0	47	39
Double Blind Phase - 28 Weeks Relapse criteria met	0	43	58
Double Blind Phase - 28 Weeks Administrative	0	5	2

Baseline Characteristics

PEARL Schizophrenia Maintenance

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lurasidone n=144 Participants During double blind phase subjects received Lurasidone flexibly dosed 40 or 80 mg once daily	Placebo n=141 Participants During double blind phase subjects received matching placebo.	Total n=285 Participants Total of all reporting groups
Age, Continuous	43.0 years STANDARD_DEVIATION 11.38 • n=99 Participants	42.4 years STANDARD_DEVIATION 12.25 • n=107 Participants	42.7 years STANDARD_DEVIATION 11.80 • n=206 Participants
Age, Categorical <=18 years	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	142 Participants n=99 Participants	140 Participants n=107 Participants	282 Participants n=206 Participants
Age, Categorical >=65 years	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Sex: Female, Male Female	54 Participants n=99 Participants	53 Participants n=107 Participants	107 Participants n=206 Participants
Sex: Female, Male Male	90 Participants n=99 Participants	88 Participants n=107 Participants	178 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	72 Participants n=99 Participants	62 Participants n=107 Participants	134 Participants n=206 Participants
Race (NIH/OMB) White	65 Participants n=99 Participants	71 Participants n=107 Participants	136 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=99 Participants	5 Participants n=107 Participants	10 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=99 Participants	9 Participants n=107 Participants	16 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	137 Participants n=99 Participants	132 Participants n=107 Participants	269 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment France	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Region of Enrollment Serbia	9 participants n=99 Participants	11 participants n=107 Participants	20 participants n=206 Participants
Region of Enrollment United States	103 participants n=99 Participants	97 participants n=107 Participants	200 participants n=206 Participants
Region of Enrollment Slovakia	11 participants n=99 Participants	11 participants n=107 Participants	22 participants n=206 Participants
Region of Enrollment Russian Federation	7 participants n=99 Participants	9 participants n=107 Participants	16 participants n=206 Participants
Region of Enrollment South Africa	10 participants n=99 Participants	11 participants n=107 Participants	21 participants n=206 Participants
Region of Enrollment Italy	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants

PRIMARY outcome

Timeframe: Double-blind phase - 28 Weeks

The Kaplan-Meier method is used for the estimation.

Outcome measures

Outcome measures
Measure	Lurasidone n=144 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=141 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Time to First Relapse Event During Double-blind Phase	NA days Interval 174.0 to Median and upper limit of the confidence interval could not be estimated. The median is not estimable for lurasidone because fewer than half of the subjects (43) had first relapse.	192 days Interval 113.0 to Upper limit of the confidence interval could not be estimated.

SECONDARY outcome

Timeframe: Double-blind phase - 28 weeks

The Kaplan-Meier method was used for estimation.

Outcome measures

Outcome measures
Measure	Lurasidone n=144 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=141 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Time to All-cause Discontinuation	148 days Interval 106.0 to Upper limit of the confidence interval could not be estimated.	115 days Interval 82.0 to 148.0

SECONDARY outcome

Timeframe: Double-Blind phase - 28 Weeks

The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items and three scales: the Positive scale contains seven questions to assess delusions, conceptual disorganization, hallucinations behavior, excitement, grandiosity, suspiciousness/persecution, and hostility; the Negative scale contains seven questions to assess blunted effect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of motivation, and similar symptoms; and the General Psychopathology subscale addresses other symptoms such as anxiety, somatic concern, and disorientation. 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 total score is the sum of all 30 items and ranges from 30 through 210. A higher score is associated with greater illness severity.

Outcome measures

Outcome measures
Measure	Lurasidone n=144 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=141 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Change From Double-blind Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score	8.3 units on a scale Standard Error 1.33	12.4 units on a scale Standard Error 1.33

SECONDARY outcome

Timeframe: Double-blind phase - 28 Weeks

The CGI-S score is a single value, clinician-rated assessment of 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.

Outcome measures

Outcome measures
Measure	Lurasidone n=144 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=141 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Change From Double-blind Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score	0.44 units on a scale Standard Error 0.087	0.74 units on a scale Standard Error 0.087

SECONDARY outcome

Timeframe: Double-blind phase - 28 Weeks

Population: There were four Lurasidone subjects and 2 placebo subjects that had no post-baseline MADRS assessment.

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.

Outcome measures

Outcome measures
Measure	Lurasidone n=140 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=139 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Change From Double-blind Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	2.5 units on a scale Standard Error 0.63	3.6 units on a scale Standard Error 0.63

SECONDARY outcome

Timeframe: Double-blind phase - 28 Weeks

Population: There were 5 Lurasidone subjects and 3 placebo subjects that had no post-baseline SF-12 assessment.

The SF-12v2 is a self-administered, multipurpose short-form (SF) generic measure of health status. It was developed to be a shorter, yet valid, alternative to the SF-36 for use in large surveys of general and specific populations as well as in large longitudinal studies of health outcomes. The 12 items in the SF-12v2 are a subset of those in the SF-36; SF-12v2 includes one or two items from each of the eight health concepts with higher scores indicative of higher functioning and better health. The Physical Component Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health scales. Physical Composite Scores (PCS) is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

Outcome measures

Outcome measures
Measure	Lurasidone n=139 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=138 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Change From Double-blind Baseline in Short Form-12v2 Health Survey (SF-12v2) Physical Component Score	0.398 units on a scale Standard Error 0.5354	-1.341 units on a scale Standard Error 0.5373

SECONDARY outcome

Timeframe: Double-blind phase - 28 Weeks

Population: There were 19 Lurasidone subjects and 20 placebo subjects that had no post-baseline assessment.

The modified SLOF scale is designed to measure directly observable behavioral functioning and daily living skills of patients with chronic mental illness. The modified SLOF consists of 24 items divided into two subscales: Social functioning (comprised of 7 items from interpersonal relationships section) and Community Living Skills (comprised of 17 items from activities and work skills sections). Each item is rated on a 5-point scale and mapped to 0 to 4 with a higher score indicating worse condition. The total score will be the sum of all 24 items and ranges from 0 to 96.

Outcome measures

Outcome measures
Measure	Lurasidone n=125 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=121 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Change From Double-blind Baseline in Modified Specific Levels of Functioning (SLOF) Total Score	0.8 units on a scale Standard Error 0.88	3.2 units on a scale Standard Error 0.89

SECONDARY outcome

Timeframe: Double-blind phase - 28 Weeks

Population: There were 6 Lurasidone subjects and 2 placebo subjects that had no post-baseline assessment.

The Brief Adherence Rating Scale (BARS) is a clinician-administered adherence assessment instrument that consists of four items including three questions and a visual analog rating scale (VAS) to assess the percentage (0 - 100%) of doses taken by the subject in the previous month.

Outcome measures

Outcome measures
Measure	Lurasidone n=138 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=139 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Brief Adherence Rating Scale	98.8 percentage of monthly doses taken Standard Deviation 4.42	98.9 percentage of monthly doses taken Standard Deviation 3.66

SECONDARY outcome

Timeframe: 28 Weeks - Double Blind Phase

Population: ITT Subjects who smoked

Smoking history and frequency were assessed during the study by a research staff member. During the study, smoked subjects were asked about the average number of cigarettes per day they smoked over the last week.

Outcome measures

Outcome measures
Measure	Lurasidone n=47 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=49 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Smoking Questionnaire (Average Number of Cigarettes Per Day) at Week 28 (LOCF)	10.0 number of cigarettes smoked daily Standard Deviation 12.76	8.2 number of cigarettes smoked daily Standard Deviation 8.97

SECONDARY outcome

Timeframe: Open Label Baseline

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.

The ITA assessment will be administered by a research staff member. The response is recorded on a 10-point scale, with 0 = "Not at all" and 9 = "Extremely". The ITA allowed the site to capture data regarding dropout risk. The following question was completed at the screening visit: "How likely is it that you will complete the study?"

Outcome measures

Outcome measures
Measure	Lurasidone n=143 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=140 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
Intent to Attend (ITA) Assessment at Open-label Baseline	7.9 units on a scale Standard Deviation 1.48	8.0 units on a scale Standard Deviation 1.47

OTHER_PRE_SPECIFIED outcome

Timeframe: Double-blind phase - 28 Weeks

Population: There were 5 Lurasidone subjects and 3 placebo subjects that had no post-baseline assessment.

The EQ-5D is a self-administered, standardized measure of health states consisting of two parts: EQ-5D descriptive system consisting of one question in each of five dimensions (mobility, self-care, pain, usual activities, and anxiety) with three possible response levels per question, classifying patients into one of 243 distinct health states, and a 20-cm visual analogue health status rating. The 20-cm visual analog scale (VAS) has endpoints labeled "best imaginable health state" and "worst imaginable health state" that are anchored at 100 and 0, respectively. Respondents are asked to indicate how they rate their own health by drawing a line from an anchor box to that point on the EQ-VAS, which best represents their own health on that day.

Outcome measures

Outcome measures
Measure	Lurasidone n=139 Participants Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating Lurasidone: Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Placebo n=138 Participants Matching placebo once daily in the evening with a meal or 30 minutes after eating Matching Placebo: Matching placebo once daily in the evening with a meal or 30 minutes after eating
EuroQol (EQ-5D): EQ-VAS Score	74.5 units on a scale Standard Deviation 19.87	68.2 units on a scale Standard Deviation 28.59

Adverse Events

All Subjects

Serious events: 59 serious events

Other events: 373 other events

Deaths: 0 deaths

Lurasidone

Serious events: 6 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 11 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director, CNS

Sunovion

Phone: 1-866-503-6351

Results disclosure agreements

Principal investigator is a sponsor employee In addition to the \<60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication; provided, if a multicenter publication is not forthcoming within 24 months following completion of study at all sites, the PI shall be free to publish.
Publication restrictions are in place

Restriction type: OTHER

Measure	All Subjects n=676 participants at risk During the Open Label Phase subjects will receive Lurasidone 40 and 80 mg, once daily in the evening with a meal or 30 minutes after eating	Lurasidone n=144 participants at risk During double blind phase subjects received Lurasidone flexibly dosed 40 or 80 mg once daily	Placebo n=141 participants at risk During double blind phase subjects received matching placebo.
Gastrointestinal disorders Nausea	10.2% 69/676 • Number of events 79 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.1% 3/144 • Number of events 3 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.71% 1/141 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Gastrointestinal disorders Vomiting	5.3% 36/676 • Number of events 45 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.69% 1/144 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/141 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Gastrointestinal disorders Abdominal discomfort	3.1% 21/676 • Number of events 31 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/144 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/141 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Gastrointestinal disorders Toothache	3.3% 22/676 • Number of events 22 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/144 • Number of events 5 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	1.4% 2/141 • Number of events 2 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Infections and infestations Nasopharyngitis	4.1% 28/676 • Number of events 32 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	1.4% 2/144 • Number of events 2 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.71% 1/141 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Infections and infestations Upper respiratory tract infection	3.4% 23/676 • Number of events 23 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.69% 1/144 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.71% 1/141 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Investigations Weight increased	2.1% 14/676 • Number of events 14 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	3.5% 5/144 • Number of events 5 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/141 • Number of events 4 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Musculoskeletal and connective tissue disorders Back pain	2.5% 17/676 • Number of events 21 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	4.2% 6/144 • Number of events 7 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.1% 3/141 • Number of events 3 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Nervous system disorders Headache	11.4% 77/676 • Number of events 116 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/144 • Number of events 5 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	3.5% 5/141 • Number of events 8 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Nervous system disorders Akathisia	13.9% 94/676 • Number of events 104 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.1% 3/144 • Number of events 3 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/141 • Number of events 4 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Nervous system disorders Dystonia	3.1% 21/676 • Number of events 23 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	1.4% 2/144 • Number of events 2 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.71% 1/141 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Nervous system disorders Somnolence	5.0% 34/676 • Number of events 38 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/144 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/141 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Nervous system disorders Dizziness	3.6% 24/676 • Number of events 28 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.69% 1/144 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/141 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Nervous system disorders Sedation	3.7% 25/676 • Number of events 27 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.69% 1/144 • Number of events 1 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	0.00% 0/141 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Psychiatric disorders Insomnia	9.2% 62/676 • Number of events 82 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	6.2% 9/144 • Number of events 10 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	7.1% 10/141 • Number of events 12 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Psychiatric disorders Anxiety	5.2% 35/676 • Number of events 43 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	4.2% 6/144 • Number of events 7 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/141 • Number of events 4 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Psychiatric disorders Agitation	3.1% 21/676 • Number of events 22 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.1% 3/144 • Number of events 3 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/141 • Number of events 5 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Psychiatric disorders Schizophrenia	0.59% 4/676 • Number of events 4 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	6.9% 10/144 • Number of events 11 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	7.8% 11/141 • Number of events 11 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.
Psychiatric disorders Psychotic disorder	0.59% 4/676 • Number of events 4 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	2.8% 4/144 • Number of events 4 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.	4.3% 6/141 • Number of events 6 • For the open label phase - all subjects SAEs and AEs were reported over 24 weeks. For the double blind phase, lurasidone and placebo, SAEs and AEs were reported over 28 weeks. The study was stopped once the anticipated number of relapses were reached.