Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder

A Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy of Flexible-Dose Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder

The goal of the current study is to determine efficacy and safety of once-weekly aripiprazole in reducing Total Tic Severity (TTS) score in children and adolescents with Tourette's Disorder.

Study Overview

• Status: Completed
• Conditions: Tourette's Disorder
• Intervention / Treatment: Drug: Aripiprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
  • Ontario
    • Toronto, Ontario, Canada, M5B 1T8
    • Whitby, Ontario, Canada, L1N 8M7
• Hungary
  • Budapest, Hungary, 1021
  • Szeged, Hungary, 6725
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 460727
  • Gyeongsang, Korea, Republic of, 626-770
  • Incheon, Korea, Republic of, 400-711
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 110-769
  • Seoul, Korea, Republic of, 143-729
• Mexico
  • Durango, Mexico, 34000
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
• Taiwan
  • Changhua, Taiwan, 50006
  • Kaohsiung, Taiwan, 83301
  • Taichung, Taiwan, 40447
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 114
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
  • California
    • Sacramento, California, United States, 95815
    • Santa Ana, California, United States, 92701
    • Wildomar, California, United States, 92595
  • Florida
    • Hialeah, Florida, United States, 33012
    • Orange City, Florida, United States, 32763
    • Saint Petersburg, Florida, United States, 33701
  • Kansas
    • Overland Park, Kansas, United States, 66211
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
  • New York
    • Staten Island, New York, United States, 10312
  • Ohio
    • Avon Lake, Ohio, United States, 44012
    • Cleveland, Ohio, United States, 44106
    • Middleburg Heights, Ohio, United States, 44130
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19139
  • Texas
    • Dallas, Texas, United States, 75230
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78258
  • Utah
    • Salt Lake City, Utah, United States, 84107
  • Washington
    • Bothell, Washington, United States, 98011

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 7 to 17 year old with diagnostic and statistical manual of mental disorders, fourth edition -text revision (DSM-IV-TR) diagnostic criteria for Tourette's disorder (TD), confirmed by the kiddie schedule for affective disorders and schizophrenia - present and lifetime version (K-SADS-PL), including the Diagnostic Supplement 5
• Has a total tic score (TTS) ≥20 on the yale global tic severity scale (YGTSS) at Screening and Baseline
• Presenting tic symptoms cause impairment in the participant's normal routines, which include academic achievement, occupational functioning, social activities, and/or relationships
• Females of childbearing potential must have a negative pregnancy test, must be practicing acceptable double-barrier methods of contraception, and must not be pregnant or lactating.
• Written informed consent form (ICF) obtained from a legally acceptable representative & informed assent at Screening as applicable by study center's Institutional review board/independent ethics committee (IRB/IEC)
• The participant, designated guardian(s) or caregiver(s) are able to comprehend and satisfactorily comply with the protocol requirements, as evaluated by the investigator.

Exclusion Criteria:

• Clinical presentation and/or history, consistent with another neurologic condition that may have accompanying abnormal movements.
• History of schizophrenia, bipolar disorder, or other psychotic disorder.
• Participant receiving psychostimulants for treatment of attention-deficit disorder/Attention-deficit hyperactivity disorder (ADD/ADHD) and who have developed and/or had exacerbations of tic disorder after initiation of stimulant treatment.
• Currently meets DSM-IV-TR criteria for a primary mood disorder.
• Severe obsessive-compulsive disorder (OCD), per children's yale-brown obsessive compulsive scale (CY-BOCS) score >16.
• Taken aripiprazole within 30 days of the Screening visit.
• Received any investigational agent in a clinical trial within 30 days prior to Screening or who were randomized into a clinical trial with Once-weekly aripiprazole at any time.
• History of neuroleptic malignant syndrome.
• Sexually active participants not using 2 approved methods of contraception; breastfeeding or pregnant.
• Risk of committing suicide
• Bodyweight lower than 16 kg
• Taken neuroleptic or antiparkinson drugs <14 days prior to randomization.
• Requiring cognitive-behavioral therapy (CBT) for TD during study.
• Participant meets DSM-IV-TR criteria for any significant psychoactive substance use disorder within the past 3 months.
• Positive drug screen
• Participant requires medications not allowed per protocol
• Use of CYP2D6 and CYP3A4 inhibitors or CYP3A4 inducers within 14 days prior to dosing and for duration of study.
• Inability to swallow tablets or tolerate oral medication
• Abnormal laboratory test results, vital signs and Electrocardiogram (ECG) results

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; Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.	Drug: Aripiprazole; Aripiprazole tablet administered orally once a week.; Other Names: ABILIFY
Placebo Comparator: Placebo; Participants randomized to placebo received aripiprazole-matching placebo, tablet, orally, QW for 8 weeks in a double-blind manner.	Drug: Placebo; Aripiprazole-matching placebo tablet administered orally once a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS)	The YGTSS is a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The TTS ranged from 0 (none) to 50 (severe) with a higher score represent more severe symptoms (greater reduction from baseline for greater improvement). Mixed Effect Repeated Measure Model (MMRM) analysis was performed.	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score	The severity of illness and efficacy of study medication for each participant were rated using the CGI-TS scale. The study physician rated the participants total improvement whether or not it is due to study treatment. All responses were compared to the participants condition at Baseline (Day 0). Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients), with lower score indicating better improvement. A negative change from Baseline indicates improvement. MMRM analysis was performed.	Baseline to Week 8
Change From Baseline in Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) Total Score	The GTS-QOL is a disease-specific patient-reported scale for the measurement of health-related quality of life in participants with Tourette's Disorder, taking into account the complexity of the clinical picture of the disease. The questionnaire consists of a 27-item Tourette's Disorder-specific scale with 4 subscales (psychological, physical, obsessional, and cognitive). The GTS-QOL total score ranged from 0 (extremely dissatisfied with life) and 100 (extremely satisfied with life). A positive change from Baseline indicates improvement. MMRM analysis was performed.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2011
• Primary Completion (Actual): November 6, 2013
• Study Completion (Actual): November 6, 2013

Study Registration Dates

• First Submitted: August 1, 2011
• First Submitted That Met QC Criteria: August 15, 2011
• First Posted (Estimate): August 17, 2011

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Tourette's Disorder; Tic disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Disease; Tourette Syndrome; 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
• Other Study ID Numbers: 31-10-272; 2011-000467-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No