Lurasidone Low-Dose - High-Dose Study Study

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01821378
• Collaborator: (none)
• Enrollment: 412
• Locations: 66
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary purpose of this study is to evaluate the efficacy of lurasidone 20 mg/day in subjects with an acute exacerbation of schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Lurasidone; Drug: Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2; Drug: Placebo	Phase 3

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 412 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Low-dose Lurasidone in Acutely Psychotic Subjects With Schizophrenia
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone 20 mg Lurasidone 20 mg once daily	Drug: Lurasidone; Lurasidone 20 mg once daily; Other Names: Latuda ; Drug: Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2; Lurasidone 80 mg once daily; Other Names: Latuda ; Drug: Placebo; Once Daily
Experimental: Lurasidone 80 mg Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Drug: Lurasidone; Lurasidone 20 mg once daily; Other Names: Latuda ; Drug: Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2; Lurasidone 80 mg once daily; Other Names: Latuda ; Drug: Placebo; Once Daily
Placebo Comparator: Placebo Placebo Comparator 20 or 80 mg once daily	Drug: Lurasidone; Lurasidone 20 mg once daily; Other Names: Latuda ; Drug: Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2; Lurasidone 80 mg once daily; Other Names: Latuda ; Drug: Placebo; Once Daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 for Lurasidone 20 mg and 80-160 mg Versus Placebo. [Baseline to 6 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. 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.

Secondary Outcome Measures

1. Change in Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 6 for Lurasidone 20 mg and 80-160 mg Versus Placebo. [Baseline to 6 Weeks]

   The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale (0-7), where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes.

2. Change From Baseline to Week 6 for the Lurasidone 20 mg, and Lurasidone 80 - 160 mg Groups Versus the Placebo Group in the Montgomery-Asberg Depression Rating Scale Total Score [Baseline to 6 Weeks]

   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.

3. Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Score (PANSS) Total Score at Week 6 [6 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. 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.

4. Change From Week 2 to Week 6 for the ENR (Early Non-responders) Lurasidone 160mg Group vs the ENR (Early Non-responders) Lurasidone 80 mg Group in the Following: PANSS Total Score [week 2 to week 6]

   The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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.

5. Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the MADRS Total Score [baseline to week 6]

   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.

6. Change From Week 2 to Week 6 for ENR Lurasidone 80 mg vs. ENR Lurasidone 160 mg in CGI-S Score [week 2 to week 6]

   The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale (0-7), where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes.

7. Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the PANSS Total Score [Baseline to week 6]

   The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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.

8. Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the CGI-S Score [baseline to week 6]

   The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale, where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes. Reason for the discrepancy of the LS mean (SE) for placebo in outcome 2 and outcome 9 is because the different MMRM model used in outcome 2 and outcome 9. The treatment groups included in the MMRM model for outcome 2 are placebo, lurasidone 20 mg, and lurasidone 80-160 mg. The treatment groups included in the MMRM model for outcome 9 are placebo, ENR lurasidone 80 mg, and ENR lurasidone 160 mg.

Other Outcome Measures

1. Change From Baseline to Week 6 for the Lurasidone 20 mg and Lurasidone 80 - 160 mg Groups Compared to the Placebo Group in the GAF Score [6 Weeks]

   The GAF is a numeric scale (0 through 100) that measures a patient's overall level of psychological, social, and occupation functioning. It is designed to guide clinicians through a methodical and comprehensive consideration of all aspects of a patient's symptoms and functioning. The scale begins at 100 - superior functioning - to 0 - inadequate information.

2. Change From Baseline to Week 6 for the Lurasidone 20 mg and Lurasidone 80 - 160 mg Groups Compared to the Placebo Group in the Euroqol (EQ-5D) Index Score [6 weeks]

   The EQ-5D is a standardized measure of health state consisting of two parts: a) EQ-5D measuring mobility, self-care, pain/discomfort, usual activities, and anxiety/depression on a 0 2 scale with lower scores indicating improvement, and b) a 20-cm visual analogue scale (VAS) for health status rating on a 0-100 scale with higher scores indicating improvement. EQ-5D health states, defined by the EQ-5D descriptive system, may be converted into a single summary index (i.e. the EQ-5D index score) by applying a formula that essentially attaches values (also called weights) to each of the levels in each dimension. The EQ-5D Index scores ranged from -0.429 to 1.000. Generally higher observed EQ-5D Index scores indicate a better degree of health.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Exclusion Criteria:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

2. history of treatment with clozapine for refractory psychosis

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

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

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

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

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

• Subject has a history of neuroleptic malignant syndrome.

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

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

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

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

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

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

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

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

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

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Woodland International Research Group, Inc.	Little Rock	Arkansas	United States	72211
2	Comprehensive Clinical Development	Cerritos	California	United States	90703
3	Synergy Clinical Research of Escondido	Escondido	California	United States	92025
4	Apostle Clinical Trials, Inc.	Long Beach	California	United States	90813
5	Cnri, Llc	Los Angeles	California	United States	90660
6	Pasadena Research Institute	Pasadena	California	United States	91106
7	Cnri, Llc	San Diego	California	United States	92102
8	University of California San Diego Medical Center	San Diego	California	United States	92103
9	Collaborative Neuroscience Network, Inc.	Torrance	California	United States	90502
10	Western Affiliated Research Institute	Denver	Colorado	United States	80209
11	Florida Clinical Research Center, LLC - PARENT	Maitland	Florida	United States	32751
12	University of Miami Medical Center	Miami	Florida	United States	33136
13	Florida Clinical Research Center, LLC	Orlando	Florida	United States	32810
14	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30308
15	iResearch Atlanta, LLC	Decatur	Georgia	United States	30030
16	Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.	Wichita	Kansas	United States	67214
17	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana	United States	70629
18	Center for Behavioral Health, LLC	Rockville	Maryland	United States	20850
19	St. Charles Psychiatric Associates	St. Charles	Missouri	United States	63301
20	Midwest Research Group	St. Charles	Missouri	United States	63304
21	Neurobehavioral Research, Inc.	Cedarhurst	New York	United States	11516
22	Comprehensive Clinical Development- Holliswood Hospital	Holliswood	New York	United States	11423
23	Midwest Clinical Research Center, LLC	Dayton	Ohio	United States	45417
24	CRILifetree	Philadelphia	Pennsylvania	United States	19139
25	FutureSearch Clinical Trials, L.P.	Austin	Texas	United States	78731
26	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
27	Pillar Clinical Research, LLC	Dallas	Texas	United States	75243
28	Bayou Clinical Research, Ltd.	Houston	Texas	United States	77007
29	E.S.E. Hospital Mental de Antioquia	Bello		Colombia
30	Centro de Investigaciones del Sistema Nervioso Limitada - Grupo CISNE Ltda	Bogota		Colombia
31	Instituto Colombiano del Sistema Nervioso - Clinica Montserrat	Bogota		Colombia
32	Spitalul Universitar de Urgenta Militar Central "Dr Carol Davila"	Bucuresti		Romania	010825
33	Spitalul de Psihiatrie Titan "Dr Constantin Gorgos"	Bucuresti		Romania	030442
34	Spitalul Clinic de Psihiatrie Prof. Dr. Alexandru Obregia	Bucuresti		Romania	041914
35	Spitalul Clinic de Neuropsihiatrie Craiova	Craiova		Romania	200473
36	Spitalul Judetean de Urgenta "Sf. Pantelimon" Focsani	Focsani		Romania	620165
37	Spitalul de Psihiatrie "Elisabeta Doamna"	Galati		Romania	800179
38	Spitalul Clinic de Psihiatrie Socola	Iasi		Romania	700282
39	Spitalul Judetean de Urgenta Pitesti	Pitesti		Romania	110069
40	Spitalul Judetean de Urgenta Targoviste	Targoviste		Romania	130086
41	SHI Arkhangelsk Regional Clinical Psychiatric Hospital	Arkhangelsk		Russian Federation	163530
42	SHI Reg Clinical Specialized Psychoneurological Hospital #1	Chelyabinsk		Russian Federation
43	Kemerovo Regional Clinical Psychiatric Hospital	Kemerovo		Russian Federation	650036
44	GUZ Lipetsk Regional psychoneurological Hospital #1	Lipetsk region		Russian Federation	399313
45	Moscow Region Psychiatric Hospital #5	Moscow Region		Russian Federation	142601
46	SBHI "Samara Psychiatric Clinic"	Samara		Russian Federation	443016
47	MHI City Clinical Hospital #2 named after V.I. Razumovsky	Saratov		Russian Federation	410028
48	FSBI "Bekhterev Psychoneurological Research Institute SPb Russia"	St Petersburg		Russian Federation	192019
49	City Psychiatric Hospital of St. Nikolay Chudotvorets	St. Petersburg		Russian Federation	190121
50	City Psychiatric Hospital #4	St. Petersburg		Russian Federation	191119
51	SPHI "City Mental Hospital #3 n.a. I.I.Skvortsov-Stepanov"	St. Petersburg		Russian Federation	197341
52	FSBI "Research Institute for Mental Health" of Siberian branch of RAMS	Tomsk		Russian Federation	634014
53	Nemocnica s poliklinikou Prievidza so sidlom v Bojniciach	Bojnice		Slovakia	97201
54	Univerzitna nemocnica Bratislava, Nemocnica Ruzinov	Brastislava		Slovakia	82605
55	Psychiatricka nemocnica Hronovce	Hronovce		Slovakia	93561
56	Psychiatricka nemocnica Michalovce, n.o.	Michalovce		Slovakia	071 01
57	Vseobecna nemocnica Rimavska Sobota	Rimavska Sobota		Slovakia	97901
58	Nemocnica s poliklinikou sv. Barbory Roznava a.s.	Roznava		Slovakia	04801
59	Donetsk M. Gorkyi NMU Ch of Psychiatry, Narcology and MP CT&PI RCPsH	Donetsk		Ukraine	83008
60	Regional Psychoneurological Hospital #3	Ivano-Frankivsk		Ukraine	76014
61	SMPI Central Clinical Hospital of Ukrzaliznytsia	Kharkiv		Ukraine	61103
62	CI Kherson Regional Psychiatric Hospital of Kherson RC	Kherson,Vil. Stepanivka		Ukraine	73488
63	Kyiv City Clinical Psychoneurological Hospital #1	Kyiv		Ukraine	04080
64	Odesa Regional Psychoneurogical Dispensary	Odesa		Ukraine	65014
65	SI S.I. Heorhievskyi CSMU Ch of PPN with the Course of G&MP CRI CPH #1	Simferopol		Ukraine	95006
66	M.I. Pyrogov VNMU Ch of Psych&Nar BO CI O.I. Yuschenko VRPsH	Vinnytsia		Ukraine	21005

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Lurasidone Medical Director, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT01821378
• Other Study ID Numbers: D1050303; 2012-005271-14
• First Posted: Apr 1, 2013
• Last Update Posted: Jul 21, 2016
• Last Verified: Jul 1, 2016

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

Study Results

Participant Flow

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80 mg - 160 mg	Placebo
Arm/Group Description	Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2: Lurasidone 80 mg once daily Placebo: Once Daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2 Lurasidone: Lurasidone 20 mg once daily Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2: Lurasidone 80 mg once daily Placebo: Once Daily	Placebo Comparator 20 or 80 mg once daily Lurasidone: Lurasidone 20 mg once daily Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2: Lurasidone 80 mg once daily Placebo: Once Daily
Period Title: Overall Study
STARTED	101	199	112
COMPLETED	74	145	70
NOT COMPLETED	27	54	42

Baseline Characteristics

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo	Total
Arm/Group Description	Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily	Total of all reporting groups
Overall Participants	101	198	112	411
Age (Count of Participants)
<=18 years	0 0%	4 2%	0 0%	4 1%
Between 18 and 65 years	99 98%	192 97%	112 100%	403 98.1%
>=65 years	2 2%	2 1%	0 0%	4 1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.5 (10.96)	40.5 (11.44)	40.7 (11.58)	40.8 (11.34)
Sex: Female, Male (Count of Participants)
Female	36 35.6%	79 39.9%	34 30.4%	149 36.3%
Male	65 64.4%	119 60.1%	78 69.6%	262 63.7%
Region of Enrollment (participants) [Number]
Colombia	3 3%	9 4.5%	7 6.3%	19 4.6%
Russian Federation	23 22.8%	49 24.7%	27 24.1%	99 24.1%
Romania	22 21.8%	38 19.2%	18 16.1%	78 19%
United States	31 30.7%	59 29.8%	38 33.9%	128 31.1%
Ukraine	16 15.8%	31 15.7%	13 11.6%	60 14.6%
Slovakia	6 5.9%	12 6.1%	9 8%	27 6.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6 for Lurasidone 20 mg and 80-160 mg Versus Placebo.
Description	The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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.
Time Frame	Baseline to 6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population - there was one subject randomized but not treated with study medication, therefore excluded from ITT population

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo
Arm/Group Description	Lurasidone 20 mg once daily Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily
Measure Participants	101	198	112
Least Squares Mean (Standard Error) [units on a scale]	-17.6 (1.93)	-24.9 (1.40)	-14.5 (1.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.255
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -8.4 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<-0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-10.3
	Confidence Interval	(2-Sided) 95%; -14.9 to -5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 6 for Lurasidone 20 mg and 80-160 mg Versus Placebo.
Description	The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale (0-7), where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes.
Time Frame	Baseline to 6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo
Arm/Group Description	Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily
Measure Participants	101	198	112
Least Squares Mean (Standard Error) [units on a scale]	-0.93 (0.105)	-1.30 (0.076)	-0.73 (0.103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.169
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 95%; -0.83 to -0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 6 for the Lurasidone 20 mg, and Lurasidone 80 - 160 mg Groups Versus the Placebo Group in the Montgomery-Asberg Depression Rating Scale 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.
Time Frame	Baseline to 6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population - only 379 subjects had at least one post-baseline MADRS assessment.

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily
Measure Participants	93	178	108
Least Squares Mean (Standard Error) [units on a scale]	-2.0 (0.57)	-3.7 (0.41)	-1.7 (0.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.706
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.8 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-2.0
	Confidence Interval	(2-Sided) 95%; -3.3 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Proportion of Subjects Who Achieve a Response, Defined as 20% or Greater Improvement From Baseline in Positive and Negative Syndrome Score (PANSS) Total Score at Week 6
Description	The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo
Arm/Group Description	Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily
Measure Participants	101	198	112
Number [percentage of participants]	44 43.6%	53 26.8%	73 65.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.173
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 0.8 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 95%; 2.0 to 5.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Week 2 to Week 6 for the ENR (Early Non-responders) Lurasidone 160mg Group vs the ENR (Early Non-responders) Lurasidone 80 mg Group in the Following: PANSS Total Score
Description	The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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.
Time Frame	week 2 to week 6

Outcome Measure Data

Analysis Population Description

ENR (early non-responders) Intent to treat (ITT) population: of the 199 subjects who randomized to 80 mg group, only 95 subjects are early non-responders at week 2, therefore they are included in the ENR ITT population.

Arm/Group Title	ENR Lurasidone 80 mg	ENR Lurasidone 160 mg
Arm/Group Description	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 80 mg/day at week 2.	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 160 mg/day at week 2.
Measure Participants	52	43
Least Squares Mean (Standard Error) [units on a scale]	-8.9 (2.20)	-16.6 (2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Lurasidone 80-160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-7.7
	Confidence Interval	(2-Sided) 95%; -14.3 to -1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the 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.
Time Frame	baseline to week 6

Outcome Measure Data

Analysis Population Description

ENR (early non-responders) Intent to treat (ITT) population: of the 199 subjects who randomized to 80 mg group, only 95 subjects are early non-responders at week 2, therefore they are included in the ENR ITT population (Lurasidone 20 mg subjects are not included in the ENR ITT population).

Arm/Group Title	ENR Lurasidone 80 mg	ENR Lurasidone 160 mg	Placebo
Arm/Group Description	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 80 mg/day at week 2.	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 160 mg/day at week 2.	Randomized to Placebo group at baseline
Measure Participants	52	42	108
Least Squares Mean (Standard Error) [units on a scale]	-2.5 (0.89)	-3.5 (1.00)	-1.7 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.464
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -2.9 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.122
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; -4.1 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Other Pre-specified Outcome

Title	Change From Baseline to Week 6 for the Lurasidone 20 mg and Lurasidone 80 - 160 mg Groups Compared to the Placebo Group in the GAF Score
Description	The GAF is a numeric scale (0 through 100) that measures a patient's overall level of psychological, social, and occupation functioning. It is designed to guide clinicians through a methodical and comprehensive consideration of all aspects of a patient's symptoms and functioning. The scale begins at 100 - superior functioning - to 0 - inadequate information.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily
Measure Participants	101	198	112
Least Squares Mean (Standard Error) [units on a scale]	11.5 (1.43)	15.8 (1.04)	9.2 (1.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 95%; -1.7 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	6.6
	Confidence Interval	(2-Sided) 95%; 3.2 to 10.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Week 2 to Week 6 for ENR Lurasidone 80 mg vs. ENR Lurasidone 160 mg in CGI-S Score
Description	The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale (0-7), where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes.
Time Frame	week 2 to week 6

Outcome Measure Data

Analysis Population Description

ENR Intent to treat population

Arm/Group Title	ENR Lurasidone 80 mg	ENR Lurasidone 160 mg
Arm/Group Description	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 80 mg/day at week 2.	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 160 mg/day at week 2.
Measure Participants	52	43
Least Squares Mean (Standard Error) [units on a scale]	-0.61 (0.116)	-0.96 (0.134)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Lurasidone 80-160 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.052
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.70 to 0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Other Pre-specified Outcome

Title	Change From Baseline to Week 6 for the Lurasidone 20 mg and Lurasidone 80 - 160 mg Groups Compared to the Placebo Group in the Euroqol (EQ-5D) Index Score
Description	The EQ-5D is a standardized measure of health state consisting of two parts: a) EQ-5D measuring mobility, self-care, pain/discomfort, usual activities, and anxiety/depression on a 0 2 scale with lower scores indicating improvement, and b) a 20-cm visual analogue scale (VAS) for health status rating on a 0-100 scale with higher scores indicating improvement. EQ-5D health states, defined by the EQ-5D descriptive system, may be converted into a single summary index (i.e. the EQ-5D index score) by applying a formula that essentially attaches values (also called weights) to each of the levels in each dimension. The EQ-5D Index scores ranged from -0.429 to 1.000. Generally higher observed EQ-5D Index scores indicate a better degree of health.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population: there are only 368 subjects who had at least one post-baseline Euroqol (EQ-5D) assessments.

Arm/Group Title	Lurasidone 20 mg	Lurasidone 80-160 mg	Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg once daily	Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2	Placebo: Once Daily
Measure Participants	92	173	103
Least Squares Mean (Standard Error) [units on a scale]	0.041 (0.024)	0.095 (0.018)	-0.042 (0.023)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.084
	Confidence Interval	(2-Sided) 95%; 0.018 to 0.149
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.138
	Confidence Interval	(2-Sided) 95%; 0.081 to 0.194
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the PANSS Total Score
Description	The PANSS is an interview-based measure of the severity of psychopathology in adults with psychotic disorders. The measure is comprised of 30 items. 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.
Time Frame	Baseline to week 6

Outcome Measure Data

Analysis Population Description

ENR (early non-responders) Intent to treat (ITT) population: of the 199 subjects who randomized to 80 mg group, only 95 subjects are early non-responders at week 2, therefore they are included in the ENR ITT population (Lurasidone 20 mg subjects are not included in the ENR ITT population).

Arm/Group Title	ENR Lurasidone 80 mg	ENR Lurasidone 160 mg	Placebo
Arm/Group Description	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 80 mg/day at week 2.	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 160 mg/day at week 2.	Randomized to Placebo group at baseline
Measure Participants	52	43	112
Least Squares Mean (Standard Error) [units on a scale]	-14.4 (2.69)	-21.7 (3.00)	-14.4 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -6.6 to 6.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.044
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) 95%; -14.4 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline to Week 6 for the ENR Lurasidone 80mg and ENR Lurasidone 160mg Groups vs the Placebo in the CGI-S Score
Description	The CGI-S is a clinician-rated assessment of the subject's current illness state on a 7-point scale, where a higher score is associated with greater illness severity. Following a clinical interview, the CGI-S can be completed in 1-2 minutes. Reason for the discrepancy of the LS mean (SE) for placebo in outcome 2 and outcome 9 is because the different MMRM model used in outcome 2 and outcome 9. The treatment groups included in the MMRM model for outcome 2 are placebo, lurasidone 20 mg, and lurasidone 80-160 mg. The treatment groups included in the MMRM model for outcome 9 are placebo, ENR lurasidone 80 mg, and ENR lurasidone 160 mg.
Time Frame	baseline to week 6

Outcome Measure Data

Analysis Population Description

ENR (early non-responders) Intent to treat (ITT) population: of the 199 subjects who randomized to 80 mg group, only 95 subjects are early non-responders at week 2, therefore they are included in the ENR ITT population (Lurasidone 20 mg subjects are not included in the ENR ITT population).

Arm/Group Title	ENR Lurasidone 80 mg	ENR Lurasidone 160 mg	Placebo
Arm/Group Description	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 80 mg/day at week 2.	Subjects who are only non-responders on Lurasidone 80 mg/day and randomized to Lurasidone 160 mg/day at week 2.	Randomized to Placebo group at baseline
Measure Participants	52	43	112
Least Squares Mean (Standard Error) [units on a scale]	-0.83 (0.143)	-1.31 (0.160)	-0.73 (0.106)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.578
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.45 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 80-160 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.58
	Confidence Interval	(2-Sided) 95%; -0.96 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 Weeks
Arm/Group Title	Lurasidone 20 mg		Lurasidone 80-160 mg		Placebo
Arm/Group Description	Lurasidone: Lurasidone 20 mg once daily		Lurasidone 80 mg once daily initially rerandomized either to 80 mg or 160 mg at week 2 (one subject who was randomized was not treated with study drug, therefore, excluded from the safety population).		Placebo: Once Daily
All Cause Mortality
	Lurasidone 20 mg		Lurasidone 80-160 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lurasidone 20 mg		Lurasidone 80-160 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/101 (3%)		6/198 (3%)		8/112 (7.1%)
General disorders
Therapuetuc Response Delayed	0/101 (0%)	0	0/198 (0%)	0	1/112 (0.9%)	1
Injury, poisoning and procedural complications
Fall	0/101 (0%)	0	1/198 (0.5%)	1	0/112 (0%)	0
Fibula Fracture	0/101 (0%)	0	1/198 (0.5%)	1	0/112 (0%)	0
Tibia Fracture	0/101 (0%)	0	1/198 (0.5%)	1	0/112 (0%)	0
Psychiatric disorders
Schizophrenia	3/101 (3%)	3	3/198 (1.5%)	3	4/112 (3.6%)	4
Psychotic Disorder	0/101 (0%)	0	2/198 (1%)	2	3/112 (2.7%)	3
Other (Not Including Serious) Adverse Events
	Lurasidone 20 mg		Lurasidone 80-160 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/101 (42.6%)		92/198 (46.5%)		58/112 (51.8%)
Gastrointestinal disorders
Dyspepsia	2/101 (2%)	2	5/198 (2.5%)	5	4/112 (3.6%)	5
Nausea	2/101 (2%)	2	17/198 (8.6%)	21	4/112 (3.6%)	5
Diarrhoea	2/101 (2%)	2	8/198 (4%)	8	3/112 (2.7%)	3
Constipation	3/101 (3%)	4	6/198 (3%)	9	2/112 (1.8%)	2
Vomiting	0/101 (0%)	0	11/198 (5.6%)	12	1/112 (0.9%)	2
Musculoskeletal and connective tissue disorders
Myalgia	1/101 (1%)	1	0/198 (0%)	0	4/112 (3.6%)	4
Back Pain	4/101 (4%)	4	3/198 (1.5%)	3	1/112 (0.9%)	1
Nervous system disorders
Headache	10/101 (9.9%)	18	11/198 (5.6%)	12	8/112 (7.1%)	12
Somnolence	5/101 (5%)	5	6/198 (3%)	6	6/112 (5.4%)	6
Akathisia	5/101 (5%)	9	21/198 (10.6%)	24	2/112 (1.8%)	2
Sedation	3/101 (3%)	3	6/198 (3%)	6	2/112 (1.8%)	2
Tremor	2/101 (2%)	2	6/198 (3%)	6	2/112 (1.8%)	2
Dizziness	1/101 (1%)	1	6/198 (3%)	6	1/112 (0.9%)	1
Parkinsonism	1/101 (1%)	1	6/198 (3%)	6	1/112 (0.9%)	1
Psychiatric disorders
Insomnia	16/101 (15.8%)	22	21/198 (10.6%)	33	24/112 (21.4%)	33
Agitation	5/101 (5%)	5	9/198 (4.5%)	9	11/112 (9.8%)	14
Anxiety	8/101 (7.9%)	18	8/198 (4%)	9	7/112 (6.3%)	12
Restlessness	0/101 (0%)	0	6/198 (3%)	10	4/112 (3.6%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS agreement between Principal Investigator and Sponsor that restricts PI's rights to discuss or publish trial results after trial is completed. 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 post completion of study at all sites, PI shall be free to publish.