Lurasidone Pediatric Autism Study

• Sponsor: Sunovion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01911442
• Collaborator: (none)
• Enrollment: 150
• Locations: 41
• Arms: 3
• Duration (Months): 15
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of 2 fixed doses of lurasidone (20 mg/day and 60 mg/day) for 6 weeks compared with placebo in pediatric and adolescent subjects with irritability associated with autistic disorder who reside in the community setting.

Condition or Disease	Intervention/Treatment	Phase
Autism	Drug: Lurasidone 20 mg daily; Drug: Lurasidone; Drug: Placebo	Phase 3

Detailed Description

This is a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of 2 fixed doses of lurasidone (20 mg/day and 60 mg/day) for 6 weeks compared with placebo in pediatric and adolescent subjects with irritability associated with autistic disorder who reside in the community setting.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 6-Week, Randomized, Parallel, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study to Evaluate the Efficacy and Safety of Lurasidone in Children and Adolescent Subjects With Irritability Associated With Autistic Disorder
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurasidone 20 mg Lurasidone 20 mg once daily	Drug: Lurasidone 20 mg daily; Lurasidone 20 mg once daily; Other Names: Latuda
Experimental: Lurasidone 60 mg Lurasidone 60 mg once daily	Drug: Lurasidone; Lurasidone 60 mg once daily; Other Names: Latuda
Placebo Comparator: Placebo Placebo once daily	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change in Aberrant Behavior Checklist (ABC) Irritability Subscale Score at Week 6 [Baseline to 6 Weeks]

   The ABC irritability subscale score is the sum of 15 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC irritability subscale score ranges from 0 to 45. Higher values of ABC subscale scores represent greater severity of illness.

Secondary Outcome Measures

1. Change From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 6 [Baseline to 6 Weeks]

   The Clinical Global Impression - Severity of Illness (CGI-S) Scale is rated on a 7-point scale of severity with 1 = Normal, not at all ill to 7 = Among the most extremely ill patients. Higher values of CGI-S scores represent greater severity of illness.

2. Change From Baseline in Aberrant Behavior Checklist (ABC) Hyperactivity Subscale Score at Week 6 [Baseline to 6 Weeks]

   The ABC hyperactivity and noncompliance subscale score is the sum of 16 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC hyperactivity and noncompliance subscale score may range from 0 to 48. In general, higher values of ABC subscale scores represent greater severity of illness.

3. Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scales (CY-BOCS) Modified for Pervasive Developmental Disorders (PDDs) [6 Weeks]

   CY-BOCS total score ranges from 0 to 20. The higher value of CY-BOCS scores the greater severity of illness. This table is a summary of Y-BOCS compulsion total score.

4. Change From Baseline in the Caregiver Strain Questionnaire (CGSQ) [6 Weeks]

   CGSQ is a caregiver reported assessment to assesses extent to which caregivers are affected by special demands associated with caring for a child with emotional/behavioral problems. CGSQ is comprised of three subscales which range in severity from 1 to 5 (Objective Strain, Subjective Externalized Strain, Subjective Internalized Strain), The 3 subscales are calculated as the averages of the corresponding individual items. Higher scores on each indicates greater strain. A Global Strain score is calculated by summing the three subscales (Objective Strain, Subjective Externalized Strain, Subjective Internalized Strain) to provide an indication of the total impact of the special demands on the family. Global Strain scores range from 3 to 15. As with the individual subscales, higher scores indicate greater strain.

5. Proportion of Subjects Who Have CGI-I Score of 1 (Very Much Improved) or 2 (Much Improved) at Week 6 [6 Weeks]

6. Proportion of Subjects Who Have at Least 25% Reduction From Baseline to Week 6 in the ABC Irritability Subscale Score. [6 Weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent from parent(s) or legal guardian(s) with sufficient intellectual capacity to understand the study and support subjects' adherence to the study procedures must be obtained for subjects who are not emancipated. In accordance with Institutional Review Board (IRB) requirements, the subject will complete an informed assent when developmentally appropriate, to participate in the study before conduct of any study-specific procedures.

• Male or female subjects 6 to 17 years of age, inclusive, at the time of consent.

• A reliable informant (eg, parent, legal guardian, or caregiver) who has past and current direct knowledge of the subject must accompany the subject at each visit and must oversee the administration of the study drug.

• DSM-IV-TR primary diagnosis of autistic disorder confirmation of the diagnosis by a trained clinician (eg, psychiatrist, psychologist, social workers, etc) at the time of screening, by means of the Autism Diagnostic Interview, Revised (ADI-R).

• Screening and Baseline ABC irritability subscale score ≥ 18.

• Screening and Baseline CGI-S ≥ 4.

• Within 5th to 95th percentile for gender specific Growth Charts from Centers for Disease Control (CDC).

• No clinically relevant abnormal laboratory values.

• No clinically relevant abnormal vital sign values/findings

1. Females who participate in this study:

• are unable to become pregnant (eg, premenarchal, surgically sterile, etc.) -OR-

• practices true abstinence (consistent with lifestyle) and must agree to remain abstinent from signing informed consent to at least 7 days after the last dose of study drug has been taken;

-OR-

•are sexually active and willing to use a medically effective method of birth control (eg, male using condom and female using condom, diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 7 days after the last dose of study drug has been taken.

• Males must be willing to remain sexually abstinent (consistent with lifestyle) or use an effective method of birth control (eg, male using condom and female using condom, diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 7 days after the last dose of study drug has been taken.

• In the judgment of the investigator, the subject is able to swallow the size and number of study drug tablets specified per protocol (See Table 4 for study drug tablet size).

• Able to adhere to protocol-specified meal requirements during dosing.

• Have a stable living arrangement for at least 3 months prior to screening.

• Non-pharmacologic therapy (eg, behavior modification) must be stable for at least 4 weeks before screening and consistent throughout the study.

Exclusion Criteria:

• Subjects with profound intellectual disability.

• Current diagnosis of bipolar disorder, psychosis, schizophrenia or major depression, or childhood disintegrative disorder as confirmed by the MINI-Kid (as appropriate) at screening. Confirmed genetic disorders with cognitive and behavioral disturbances are also exclusionary.

• Clinically significant neurological, metabolic (including type 1 and type 2 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, carcinoma, and/or urological disorder that would pose a risk to the subjects if they were to participate in the study or that might confound the results of the study.

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.

• Evidence of any chronic organic disease of the CNS such as tumors, inflammation, active seizure disorder, vascular disorder, potential CNS related disorders that might occur in childhood- eg, Duchenne Muscular dystrophy, myasthenia gravis, or other neurologic or serious neuromuscular disorders. In addition, subjects must not have a history of persistent neurological symptoms attributable to serious head injury. Past history of febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is not exclusionary.

• If the subject has a history of seizures, the subjects must not currently be taking any antiepileptic drugs (AEDs) and be seizure-free for at least 6 months.

• Clinically significant finding(s) on physical examination determined by the investigator to pose a health concern to the subject while on study.

• A history or presence of abnormal ECG, which in the investigator's opinion is clinically significant. Screening ECGs will be centrally over-read, and eligibility will be determined based on the over-read.

• Known history or presence of clinically significant intolerance to any antipsychotic medications including but not limited to angioedema, serotonin or neuroleptic malignant syndromes, severe dystonia, or moderate to severe tardive dyskinesia.

• Clinically significant alcohol abuse/dependence or drug abuse/dependence based on Mini International Neuropsychiatric Interview for children and adolescents (MINI-Kid) criteria within the last 6 months prior to screening.

• Clinically significant orthostatic hypotension (ie, a drop in systolic blood pressure of 20 mmHg or more and/or drop in diastolic blood pressure of 10 mmHg or more within 4 minutes of standing up).

• Presence or history (within the last year) of a medical or surgical condition (eg, gastrointestinal disease) that might interfere with the absorption, metabolism, or excretion of orally administered lurasidone.

• Positive test results at screening for:

1. Urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, cannabinoids, methamphetamine, and methadone). 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).

2. Pregnancy test (only in female subjects ≥ 11 years old).

• Lifetime history of human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS), or history of Hepatitis B or C.

• Participated in another interventional clinical trial or receiving an investigational product within 30 days prior to study drug administration.

• Use of concomitant medications that consistently prolong the QT/QTc interval within 28 days prior to randomization.

• Received depot neuroleptics unless the last injection was at least 1 month or 1 treatment cycle prior to screening, whichever is longer.

• Subject has received treatment with antidepressants within 3 days, fluoxetine hydrochloride at any time within 21 days, an MAO inhibitor within 21 days of randomization or clozapine within 120 days of randomization. Depot neuroleptics must be discontinued at least one treatment cycle prior to randomization.

• Use of any antipsychotic medication (other than study drug), carbamazepine, oxcarbazepine or fluvoxamine, within 3 days prior to randomization.

• Females who are pregnant, lactating, or likely to become pregnant during the study.

• Donation of whole blood within 60 days prior to randomization.

• Has a prolactin concentration greater than or equal to 100 ng/mL at screening.

• Subject is considered by the investigator to be at imminent risk of suicide during the study. Subject has a history of one or more serious suicide attempts (based on the investigator's judgment) in the 12 months prior to screening. Subjects determined to be at risk of suicide or injury, as assessed by the investigator at screening, will be referred for further psychiatric evaluation.

• Clinically relevant history of drug hypersensitivity to lurasidone or any components in the formulation.

• Subject requires use of concomitant medications that are potent inducers or inhibitors of the cytochrome P450 (CYP) 3A4 enzyme system (Appendix C) from signing informed consent until follow-up.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Harmonex Neuroscience Research	Dothan	Alabama	United States	36303
2	Southwest Autism Research & Resource Center	Phoenix	Arizona	United States	85006
3	Newport Beach Clinical Research Associates	Newport Beach	California	United States	92663
4	University of California San Francisco Medical Center	San Francisco	California	United States	94143
5	Florida Clinical Research Center, LLC	Bradenton	Florida	United States	34201
6	Sarkis Clinical Trials - Parent	Gainesville	Florida	United States	32607
7	Palm Springs Research Institute Inc	Hialeah	Florida	United States	33012
8	Florida Clinical Research Center, LLC	Maitland	Florida	United States	32751
9	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32806
10	University of South Florida	Saint Petersburg	Florida	United States	33701
11	Medical Research Group of Central Florida	Sanford	Florida	United States	32771
12	University of South Florida	Tampa	Florida	United States	33613-4706
13	Institute for Behavioral Medicine, LLC	Smyrna	Georgia	United States	30080
14	Capstone Clinical Research, Inc.	Libertyville	Illinois	United States	60048
15	Baber Research Group	Naperville	Illinois	United States	60563
16	University of Kentucky	Lexington	Kentucky	United States	40509
17	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana	United States	70629
18	Kennedy Krieger Institute	Baltimore	Maryland	United States	21287
19	NeuroScientific Insights	Rockville	Maryland	United States	20852
20	Neurobehaviorial Medicine Group, PLLC	Bloomfield Hills	Michigan	United States	48302
21	Center for Psychiatry and Behavioral Medicine, Inc.	Las Vegas	Nevada	United States	89128
22	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07753
23	Childrens Specialized Hospital	Toms River	New Jersey	United States	08755
24	Montefiore Medical Center PRIME	Bronx	New York	United States	10467
25	Finger Lakes Clinical Research	Rochester	New York	United States	14618
26	Richmond Behavioral Associates	Staten Island	New York	United States	10312
27	Chapel Hill Neurology	Chapel Hill	North Carolina	United States	27517
28	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
29	The Ohio State University Nisonger Center	Columbus	Ohio	United States	43210
30	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
31	Cyn3rgy Research & Development	Gresham	Oregon	United States	97030
32	Suburban Research Associates	Media	Pennsylvania	United States	19063
33	Segal Institute for Clinical Research	Charleston	South Carolina	United States	29407
34	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee	United States	38119
35	Family Psychiatry of The Woodlands, P.A.	The Woodlands	Texas	United States	77381
36	Ericksen Research & Development, LLC	Clinton	Utah	United States	84015
37	CRI Lifetree	Salt Lake City	Utah	United States	84106
38	University of Virginia	Charlottesville	Virginia	United States	22903
39	Neuroscience, Inc.	Herndon	Virginia	United States	20170
40	Carilion Clinic	Roanake	Virginia	United States	24014
41	Pacific Institute of Medical Sciences	Bothell	Washington	United States	98011

Sponsors and Collaborators

• Sunovion

Investigators

• Study Director: Lurasidone Medical Director, MD, Sunovion

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sunovion
• ClinicalTrials.gov Identifier: NCT01911442
• Other Study ID Numbers: D1050325
• First Posted: Jul 30, 2013
• Last Update Posted: Feb 25, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Sunovion: Autism, Lurasidone, Latuda
• Additional relevant MeSH terms: Autistic Disorder; Lurasidone Hydrochloride

Study Results

Participant Flow

Recruitment Details	Participants were recruited from 46 centers in the United States between August 2013 and October 2014
Pre-assignment Detail	Participants were screened and washed out up to 21 days.

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo
Arm/Group Description	Subjects received 20 mg/day from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
Period Title: Overall Study
STARTED	49	51	50
COMPLETED	43	47	38
NOT COMPLETED	6	4	12

Baseline Characteristics

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo	Total
Arm/Group Description	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit	Total of all reporting groups
Overall Participants	49	51	49	149
Age (Count of Participants)
<=18 years	49 100%	51 100%	49 100%	149 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 20.4%	8 15.7%	9 18.4%	27 18.1%
Male	39 79.6%	43 84.3%	40 81.6%	122 81.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 22.4%	7 13.7%	7 14.3%	25 16.8%
Not Hispanic or Latino	38 77.6%	44 86.3%	42 85.7%	124 83.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2%	1 2%	0 0%	2 1.3%
Asian	0 0%	1 2%	1 2%	2 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	10 20.4%	9 17.6%	5 10.2%	24 16.1%
White	35 71.4%	38 74.5%	42 85.7%	115 77.2%
More than one race	0 0%	1 2%	1 2%	2 1.3%
Unknown or Not Reported	3 6.1%	1 2%	0 0%	4 2.7%
Region of Enrollment (participants) [Number]
United States	49 100%	51 100%	49 100%	149 100%

Outcome Measures

1. Primary Outcome

Title	Change in Aberrant Behavior Checklist (ABC) Irritability Subscale Score at Week 6
Description	The ABC irritability subscale score is the sum of 15 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC irritability subscale score ranges from 0 to 45. Higher values of ABC subscale scores represent greater severity of illness.
Time Frame	Baseline to 6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population includes all randomized subjects who receive at least one dose of study medication and have at least one post-baseline assessment in any efficacy variable.

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo
Arm/Group Description	Subjects received 20 mg/day from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
Measure Participants	48	51	49
Least Squares Mean (Standard Error) [units on a scale]	8.8 (1.5)	9.4 (1.43)	7.5 (1.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg Once Daily, Placebo
	Comments	LS Mean, LS mean difference and the associated 95% Cl and p-value for change from baseline are based on Mixed Model for Repeated Measures (MMRM).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5463
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -5.6 to 3.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.15
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 60 mg Once Daily, Placebo
	Comments	LS Mean, LS mean difference, and the associated 95% CI and p-value for change from baseline are based on Mixed Model for Repeated Measures.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3592
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -6.1 to 2.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.09
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 6
Description	The Clinical Global Impression - Severity of Illness (CGI-S) Scale is rated on a 7-point scale of severity with 1 = Normal, not at all ill to 7 = Among the most extremely ill patients. Higher values of CGI-S scores represent greater severity of illness.
Time Frame	Baseline to 6 Weeks

Outcome Measure Data

Analysis Population Description

Intent to treat population. 49 in the placebo arm is correct. One subject in the placebo group did not receive the study medication, and therefore that subject was removed from the ITT population. A total of 50 subjects were randomized and 49 subjects were included in the placebo group of the ITT population.

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo
Arm/Group Description	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
Measure Participants	48	51	49
Least Squares Mean (Standard Error) [units on a scale]	-1.1 (0.17)	-1.0 (0.16)	-0.7 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 20 mg Once Daily, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1755
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments	This is due to rounding. the LSM for Lurasidone 20 mg/d at week 6 was -1.069 vs -0.734 for placebo group. So the LSM of the treatment difference between Lurasidone 20 mg/d and placebo was 0.335 if 3 decimals are reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lurasidone 60 mg Once Daily, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2402
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Aberrant Behavior Checklist (ABC) Hyperactivity Subscale Score at Week 6
Description	The ABC hyperactivity and noncompliance subscale score is the sum of 16 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC hyperactivity and noncompliance subscale score may range from 0 to 48. In general, higher values of ABC subscale scores represent greater severity of illness.
Time Frame	Baseline to 6 Weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo
Arm/Group Description	Subjects received 20 mg/day from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
Measure Participants	48	51	49
Least Squares Mean (Standard Error) [units on a scale]	-9.7 (1.50)	-6.6 (1.43)	-7.1 (1.52)

4. Secondary Outcome

Title	Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scales (CY-BOCS) Modified for Pervasive Developmental Disorders (PDDs)
Description	CY-BOCS total score ranges from 0 to 20. The higher value of CY-BOCS scores the greater severity of illness. This table is a summary of Y-BOCS compulsion total score.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo
Arm/Group Description	Subjects received 20 mg/day from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
Measure Participants	48	51	49
Least Squares Mean (Standard Error) [units on a scale]	-1.0 (0.46)	-1.0 (0.44)	-1.2 (0.49)

5. Secondary Outcome

Title	Change From Baseline in the Caregiver Strain Questionnaire (CGSQ)
Description	CGSQ is a caregiver reported assessment to assesses extent to which caregivers are affected by special demands associated with caring for a child with emotional/behavioral problems. CGSQ is comprised of three subscales which range in severity from 1 to 5 (Objective Strain, Subjective Externalized Strain, Subjective Internalized Strain), The 3 subscales are calculated as the averages of the corresponding individual items. Higher scores on each indicates greater strain. A Global Strain score is calculated by summing the three subscales (Objective Strain, Subjective Externalized Strain, Subjective Internalized Strain) to provide an indication of the total impact of the special demands on the family. Global Strain scores range from 3 to 15. As with the individual subscales, higher scores indicate greater strain.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Lurasidone 20 mg Once Daily	Lurasidone 60 mg Once Daily	Placebo
Arm/Group Description	Subjects received 20 mg/day from Day 1 to Week 6 Visit	Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).	Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
Measure Participants	48	51	49
Least Squares Mean (Standard Error) [units on a scale]	-1.49 (0.292)	-1.66 (0.274)	-1.35 (0.300)

6. Secondary Outcome

Title	Proportion of Subjects Who Have CGI-I Score of 1 (Very Much Improved) or 2 (Much Improved) at Week 6
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT - the current data presented is at week 6.

Arm/Group Title	Lurasidone 20 mg	Lurasidone 60 mg	Placebo
Arm/Group Description	Lurasidone 20 mg once daily Lurasidone 20 mg daily: Lurasidone 20 mg once daily	Lurasidone 60 mg once daily Lurasidone: Lurasidone 60 mg once daily	Placebo once daily Placebo: Placebo
Measure Participants	43	47	38
Number [percentage of subjects]	17	17	14

7. Secondary Outcome

Title	Proportion of Subjects Who Have at Least 25% Reduction From Baseline to Week 6 in the ABC Irritability Subscale Score.
Time Frame	6 Weeks

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Lurasidone 20 mg	Lurasidone 60 mg	Placebo
Arm/Group Description	Lurasidone 20 mg once daily Lurasidone 20 mg daily: Lurasidone 20 mg once daily	Lurasidone 60 mg once daily Lurasidone: Lurasidone 60 mg once daily	Placebo once daily Placebo: Placebo
Measure Participants	43	47	38
Number [percentage of subjects]	25	26	23

Adverse Events

Time Frame	Adverse event data were collected as spontaneous reports at all visits
Adverse Event Reporting Description	Participant flow module presents all subjects randomized. The summary of AEs is based on safety population. As explained earlier, there were 49 placebo subjects included in the safety population.
Arm/Group Title	Lurasidone 20 mg Once Daily		Lurasidone 60 mg Once Daily		Placebo
Arm/Group Description	Subjects received 20 mg/day from Day 1 to Week 6 Visit		Subjects received lurasidone 20 mg/day from Days 1-3, 40 mg/day from Days 4-6 and 60 mg/day from Day 7 to Week 6 Visit. One-time dose reduction to Lurasidone 40 mg/day may occur in Weeks 2, 3 or 4 (ie, between Day 8 to Day 29, inclusive).		Subject received placebo to match lurasidone from Day 1 to Week 6 Visit
All Cause Mortality
	Lurasidone 20 mg Once Daily		Lurasidone 60 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Lurasidone 20 mg Once Daily		Lurasidone 60 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/49 (6.1%)		2/51 (3.9%)		0/49 (0%)
General disorders
Appendicitis	0/49 (0%)	0	1/51 (2%)	1	0/49 (0%)	0
Irritability	1/49 (2%)	1	0/51 (0%)	0	0/49 (0%)	0
Injury, poisoning and procedural complications
Torus Fracture	1/49 (2%)	1	1/51 (2%)	1	0/49 (0%)	0
Upper Limb Fracture	1/49 (2%)	1	1/51 (2%)	1	0/49 (0%)	0
Other (Not Including Serious) Adverse Events
	Lurasidone 20 mg Once Daily		Lurasidone 60 mg Once Daily		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/49 (67.3%)		38/51 (74.5%)		28/49 (57.1%)
Gastrointestinal disorders
Vomiting	4/49 (8.2%)	4	14/51 (27.5%)	17	2/49 (4.1%)	2
Diarrhoea	1/49 (2%)	1	4/51 (7.8%)	4	4/49 (8.2%)	4
Nausea	2/49 (4.1%)	2	3/51 (5.9%)	6	0/49 (0%)	0
Constipation	0/49 (0%)	0	3/51 (5.9%)	3	1/49 (2%)	1
Gastritis	2/49 (4.1%)	2	0/51 (0%)	0	0/49 (0%)	0
Abdominal Discomfort	2/49 (4.1%)	2	0/51 (0%)	0	0/49 (0%)	0
General disorders
Fatigue	1/49 (2%)	1	4/51 (7.8%)	5	1/49 (2%)	1
Pyrexia	2/49 (4.1%)	2	1/51 (2%)	1	0/49 (0%)	0
Irritability	2/49 (4.1%)	2	0/51 (0%)	0	2/49 (4.1%)	2
Infections and infestations
Nasopharynigitis	5/49 (10.2%)	5	3/51 (5.9%)	4	0/49 (0%)	0
Gastroenteritis Viral	1/49 (2%)	1	1/51 (2%)	1	2/49 (4.1%)	2
Rhinitis	2/49 (4.1%)	2	0/51 (0%)	0	0/49 (0%)	0
Injury, poisoning and procedural complications
Laceration	2/49 (4.1%)	2	1/51 (2%)	1	1/49 (2%)	1
Investigations
Weight Increased	1/49 (2%)	1	4/51 (7.8%)	4	1/49 (2%)	1
Metabolism and nutrition disorders
Increased Appetite	0/49 (0%)	0	1/51 (2%)	2	3/49 (6.1%)	3
Nervous system disorders
Somnolence	3/49 (6.1%)	4	9/51 (17.6%)	10	2/49 (4.1%)	2
Akathisia	3/49 (6.1%)	5	3/51 (5.9%)	6	0/49 (0%)	0
Headache	2/49 (4.1%)	2	3/51 (5.9%)	3	3/49 (6.1%)	4
Psychomotor Hyperactivity	2/49 (4.1%)	2	2/51 (3.9%)	2	1/49 (2%)	2
Sedation	3/49 (6.1%)	3	1/51 (2%)	1	1/49 (2%)	1
Lethargy	2/49 (4.1%)	2	0/51 (0%)	0	0/49 (0%)	0
Disturbance in Attention	0/49 (0%)	0	0/51 (0%)	0	2/49 (4.1%)	2
Psychiatric disorders
Aggression	2/49 (4.1%)	3	1/51 (2%)	1	0/49 (0%)	0
Insomnia	1/49 (2%)	1	1/51 (2%)	1	5/49 (10.2%)	5
Anxiety	0/49 (0%)	0	0/51 (0%)	0	2/49 (4.1%)	2
Renal and urinary disorders
Enuresis	0/49 (0%)	0	0/51 (0%)	0	2/49 (4.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/49 (4.1%)	2	3/51 (5.9%)	3	2/49 (4.1%)	2

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.