Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Autistic Disorder

A Multicenter, Randomized, Double-blind, Flexible-dosed, Placebo-controlled, Parallel-group Clinical Trial Evaluating the Efficacy and Safety of Aripiprazole Oral Solution in Children and Adolescents With Autistic Disorder

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy, safety, tolerability and the steady-state plasma trough concentration of aripiprazole flexible-dosed in children and adolescents with a diagnosis of Autistic Disorder. Approximately 100 subjects will be randomly assigned at a 1:1 ratio to receive aripiprazole (2 to 15 mg) or placebo treatment for 8 weeks

Study Overview

• Status: Completed
• Conditions: Autistic Disorder
• Intervention / Treatment: Drug: Aripiprazole Oral Solution; Drug: Placebo Oral Solution

Detailed Description

Screening Phase: up to 42 days (consisting of a Screening Visit (V1), a washout period and Interim Screening Visit (V1a) when applicable, and a Baseline Visit (V2). The Screening Phase will serve multiple purposes: to allow for appropriate washout of prohibited medications; to allow for review of screening data; to establish a pre-treatment baseline of key outcome measures.

Treatment Phase: The duration of the treatment is 8 weeks. The purpose of the treatment phase is to evaluate the efficacy, safety, tolerability and steady-state plasma trough concentration of aripiprazole in the treatment of serious behavioral problems in children and adolescents with a diagnosis of Autistic Disorder..

Safety Follow-up Phase: All subjects will be followed up for safety (adverse events) at Day 16 after the last medication via telephone.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • 6th affiliated hospital, Peking University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent must be obtained from a legally authorized guardianprior to the initiation of any protocol-required procedures.
2. The subject and/or the designated guardian(s) or caregiver(s) are able to comprehend and satisfactorily comply with the protocol requirements, in the opinion of the Investigator.
3. The patient meets current DSM-IV-TR diagnostic criteria for Autistic Disorder and also demonstrates behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these problems. In addition, the Childhood Autism Rating Scale (CARS) score is ≥30.
4. The subject has a Clinical Global Impressions-Severity (CGI-S) score ≥ 4 AND an ABC-I subscale score ≥18 at screening (Visit 1 or Visit 1a) and baseline (V2).
5. Environmental factors can be consistent throughout the trial period.
6. The subject is a male or female child or adolescent 6 to 17 years of age (6 ≤ age ≤ 17) at Baseline (V2).

Exclusion Criteria:

1. Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study.

   Note: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone level ≥ 35 mIU/mL].

2. Women with a positive pregnancy test or who are pregnant or breastfeeding.
3. The subject has a current diagnosis of psychotic disorder such as bipolar disorder, schizophrenia, or depression.
4. The subject is currently diagnosed with another disorder on the autism spectrum, including Pervasive Developmental Disorder-Not Otherwise Specified, Asperger's Disorder, Rett's Disorder, Childhood Disintegrative Disorder or Fragile-X Syndrome.
5. The subject has a history of neuroleptic malignant syndrome.
6. The subject represents a significant risk of committing suicide based on history or routine psychiatric status examination.
7. The subject has had a seizure in the past year or the electroencephalograph examination is epileptiform discharge at screening.
8. The subject has a history of severe head trauma or stroke；
9. The subject has a history or current evidence of any unstable medical conditions (eg. history of congenital heart disease or arrhythmia, or cancer) that, in the judgment of the investigator would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial.
10. Non-pharmacological therapy (e.g., psychotherapy, behavior modification, and education training, etc.) could not be stable prior to screening and consistent throughout the study, and the subject who needs to use acupuncture and moxibustion, auditory integration, biofeedback and transcranial magnetic stimulation therapy as supplemental replacement therapy in 7 days prior to taking investigational product or during the course of the trial.
11. The subject is considered treatment resistant to antipsychotics medication, in the opinion of the Investigator, based on lack of therapeutic response to 2 different antipsychotics with reasonable doses after treatment of at least 3 weeks each.
12. The subjects considered treatment resistant to aripiprazole in the opinion of the investigator based on lack of therapeutic response to an adequate dose and duration of aripiprazole treatment.

13. The following laboratory test results, vital sign and Electrocardiograph (ECG) findings are exclusionary:

    • QTc > 450 msec (male), QTc > 470 msec (female)
    • Platelets (below the lower limit)
    • Hemoglobin (below the lower limit)
    • Neutrophils (below the lower limit)
    • AST (SGOT) or ALT (SGPT) (above the upper limit)
    • Creatinine (above the upper limit) In addition, subjects should be excluded if they have any other abnormal laboratory test result, vital sign result or ECG finding that in the investigator's judgment is clinically significant, in that it would impact the safety of the patient or the interpretation of the study results.
14. The subject weighs < 15 kg.
15. The subject has a known allergy or hypersensitivity to aripiprazole or other dihydrocarbostyrils (eg. carteolol, vesnarinone, and cilostazol).
16. The subject has participated in any clinical trials with an investigational agent within the past month.
17. Subjects who are likely to require prohibited concomitant therapy during the trial (refer to Section 7 Prohibited and Restricted Therapies).
18. Subjects who participated in a previous clinical trial of aripiprazole (with the exception of Investigator Sponsored Trials).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aripiprazole Oral Solution; 1 mg/mL, 2 ~ 15 mg/day (2 ~ 15 mL/day), taken once daily for 8 weeks. Administrate about at the same time each day, either before or after meals;	Drug: Aripiprazole Oral Solution; Aripiprazole 2~15 mg/day (2~15 mL/day); Other Names: Abilify; Aripiprazole
Placebo Comparator: Placebo Oral Solution; 2 ~ 15 mg/day (2 ~ 15 mL/day), taken once daily for 8 weeks. Administrate about at the same time each day, either before or after meals.	Drug: Placebo Oral Solution; Placebo 2~15 mg/day (2~15 mL/day); Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from Baseline to Week 8 (or endpoint) in the ABC-I score	The objective of the primary analysis is to compare the efficacy of aripiprazole flexible-dosed (2 ~ 15 mg/day) with placebo in reducing serious behavioral problems, specifically irritability, agitation and self-injurious behavior, in children and adolescents with a diagnosis of Autistic Disorder. The efficacy is assessed by assessed by change from baseline to endpoint on the Irritability Subscale of the ABC (ABC-I).	Baseline and 8 weeks (or endpoint)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician-rated CGI-I score at Week 8 (or endpoint)	The efficacy is assessed by the clinician-rated CGI-I score at Week 8	Baseline and 8 weeks (or endpoint)
Change in ABC subscale scores from Baseline to Week 8 (or endpoint)	The efficacy is assessed by changes from Baseline to Week 8 (or endpoint) in Social Withdrawal, Hyperactivity, Stereotypy and Inappropriate Speech Subscale scores of the ABC	Baseline and 8 weeks (or endpoint)
Response Rate at Week 8 (or endpoint) (or endpoint)	The response is defined as a reduction ≥25% in ABC-I score compared to the baseline, and a CGI-I score of much improved or very much improved) at Week 8 (or endpoint).The efficacy is assessed by response rate at Week 8 (or endpoint).	Baseline and 8 weeks (or endpoint)

Collaborators and Investigators

• Sponsor: Otsuka Beijing Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2018
• Primary Completion (Actual): April 21, 2020
• Study Completion (Actual): April 21, 2020

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: April 2, 2018
• First Posted (Actual): April 4, 2018

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Autistic; Aripiprazole Oral Solution
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Pharmaceutical Solutions
• Other Study ID Numbers: 031-403-00106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No