Clinical trial NCT01911442: Lurasidone Pediatric Autism Study
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autism
Keywords: Autism, Lurasidone, Latuda
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2013-07-30
Enrollment: 150
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Aberrant Behavior Checklist (ABC) Irritability Subscale Score at Week 6
timeFrame: Baseline to 6 Weeks
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 6
timeFrame: Baseline to 6 Weeks
measure: Change From Baseline in Aberrant Behavior Checklist (ABC) Hyperactivity Subscale Score at Week 6
timeFrame: Baseline to 6 Weeks
measure: Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scales (CY-BOCS) Modified for Pervasive Developmental Disorders (PDDs)
timeFrame: 6 Weeks
measure: Change From Baseline in the Caregiver Strain Questionnaire (CGSQ)
timeFrame: 6 Weeks
measure: Proportion of Subjects Who Have CGI-I Score of 1 (Very Much Improved) or 2 (Much Improved) at Week 6
timeFrame: 6 Weeks
measure: Proportion of Subjects Who Have at Least 25% Reduction From Baseline to Week 6 in the ABC Irritability Subscale Score.
timeFrame: 6 Weeks
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center
state: Arizona
city: Newport Beach
country: United States
facility: Newport Beach Clinical Research Associates
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Bradenton
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials - Parent
state: Florida
city: Hialeah
country: United States
facility: Palm Springs Research Institute Inc
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: University of South Florida
state: Florida
city: Sanford
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Smyrna
country: United States
facility: Institute for Behavioral Medicine, LLC
state: Georgia
city: Libertyville
country: United States
facility: Capstone Clinical Research, Inc.
state: Illinois
city: Naperville
country: United States
facility: Baber Research Group
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Rockville
country: United States
facility: NeuroScientific Insights
state: Maryland
city: Bloomfield Hills
country: United States
facility: Neurobehaviorial Medicine Group, PLLC
state: Michigan
city: Las Vegas
country: United States
facility: Center for Psychiatry and Behavioral Medicine, Inc.
state: Nevada
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Toms River
country: United States
facility: Childrens Specialized Hospital
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center PRIME
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Chapel Hill
country: United States
facility: Chapel Hill Neurology
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Nisonger Center
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Gresham
country: United States
facility: Cyn3rgy Research & Development
state: Oregon
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Charleston
country: United States
facility: Segal Institute for Clinical Research
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands, P.A.
state: Texas
city: Clinton
country: United States
facility: Ericksen Research & Development, LLC
state: Utah
city: Salt Lake City
country: United States
facility: CRI Lifetree
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Herndon
country: United States
facility: Neuroscience, Inc.
state: Virginia
city: Roanake
country: United States
facility: Carilion Clinic
state: Virginia
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: Lurasidone Medical Director, MD
role: STUDY_DIRECTOR
References: