Lurasidone Pediatric Autism Study

Autism Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01911442
• Other study ID #: D1050325
• Status: Completed
• Phase: Phase 3
• First received: July 22, 2013
• Last updated: January 27, 2016
• Start date: August 2013
• Est. completion date: November 2014

Study information

• Verified date: January 2016
• Source: Sunovion
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autism

Intervention

Drug:
• Lurasidone 20 mg daily
Lurasidone 20 mg once daily
• Lurasidone
Lurasidone 60 mg once daily
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Neurobehaviorial Medicine Group, PLLC	Bloomfield Hills	Michigan
United States	Pacific Institute of Medical Sciences	Bothell	Washington
United States	Florida Clinical Research Center, LLC	Bradenton	Florida
United States	Montefiore Medical Center PRIME	Bronx	New York
United States	Chapel Hill Neurology	Chapel Hill	North Carolina
United States	Segal Institute for Clinical Research	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Ericksen Research & Development, LLC	Clinton	Utah
United States	The Ohio State University Nisonger Center	Columbus	Ohio
United States	Harmonex Neuroscience Research	Dothan	Alabama
United States	Sarkis Clinical Trials - Parent	Gainesville	Florida
United States	Cyn3rgy Research & Development	Gresham	Oregon
United States	Neuroscience, Inc.	Herndon	Virginia
United States	Palm Springs Research Institute Inc	Hialeah	Florida
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	Center for Psychiatry and Behavioral Medicine, Inc.	Las Vegas	Nevada
United States	University of Kentucky	Lexington	Kentucky
United States	Capstone Clinical Research, Inc.	Libertyville	Illinois
United States	Florida Clinical Research Center, LLC	Maitland	Florida
United States	Suburban Research Associates	Media	Pennsylvania
United States	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee
United States	Baber Research Group	Naperville	Illinois
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Newport Beach Clinical Research Associates	Newport Beach	California
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Southwest Autism Research & Resource Center	Phoenix	Arizona
United States	Carilion Clinic	Roanake	Virginia
United States	Finger Lakes Clinical Research	Rochester	New York
United States	NeuroScientific Insights	Rockville	Maryland
United States	University of South Florida	Saint Petersburg	Florida
United States	CRI Lifetree	Salt Lake City	Utah
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Medical Research Group of Central Florida	Sanford	Florida
United States	Institute for Behavioral Medicine, LLC	Smyrna	Georgia
United States	Richmond Behavioral Associates	Staten Island	New York
United States	University of South Florida	Tampa	Florida
United States	Family Psychiatry of The Woodlands, P.A.	The Woodlands	Texas
United States	Childrens Specialized Hospital	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sunovion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Aberrant Behavior Checklist (ABC) Irritability Subscale Score at Week 6	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.	Baseline to 6 Weeks	No
Secondary	Change From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 6	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.	Baseline to 6 Weeks	No
Secondary	Change From Baseline in Aberrant Behavior Checklist (ABC) Hyperactivity Subscale Score at Week 6	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.	Baseline to 6 Weeks	No
Secondary	Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scales (CY-BOCS) Modified for Pervasive Developmental Disorders (PDDs)	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.	6 Weeks	No
Secondary	Change From Baseline in the Caregiver Strain Questionnaire (CGSQ)	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.	6 Weeks	No
Secondary	Proportion of Subjects Who Have CGI-I Score of 1 (Very Much Improved) or 2 (Much Improved) at Week 6		6 Weeks	No
Secondary	Proportion of Subjects Who Have at Least 25% Reduction From Baseline to Week 6 in the ABC Irritability Subscale Score.		6 Weeks	No