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

Primary Purpose

Tourette's Disorder

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aripiprazole
Placebo
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tourette's Disorder focused on measuring Tourette's Disorder, Tic disorders

Eligibility Criteria

7 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aripiprazole

Placebo

Arm Description

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.

Participants randomized to placebo received aripiprazole-matching placebo, tablet, orally, QW for 8 weeks in a double-blind manner.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
August 1, 2011
Last Updated
September 10, 2021
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01418339
Brief Title
Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
July 27, 2011 (Actual)
Primary Completion Date
November 6, 2013 (Actual)
Study Completion Date
November 6, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tourette's Disorder
Keywords
Tourette's Disorder, Tic disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
135 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aripiprazole
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants randomized to placebo received aripiprazole-matching placebo, tablet, orally, QW for 8 weeks in a double-blind manner.
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
ABILIFY
Intervention Description
Aripiprazole tablet administered orally once a week.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Aripiprazole-matching placebo tablet administered orally once a week.
Primary Outcome Measure Information:
Title
Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS)
Description
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.
Time Frame
Baseline to Week 8
Secondary Outcome Measure Information:
Title
Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score
Description
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.
Time Frame
Baseline to Week 8
Title
Change From Baseline in Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) Total Score
Description
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.
Time Frame
Baseline to Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eva Kohegyi, MD
Organizational Affiliation
Otsuka Pharmaceutical Development & Commercialization, Inc.
Official's Role
Study Director
Facility Information:
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95815
Country
United States
City
Santa Ana
State/Province
California
ZIP/Postal Code
92701
Country
United States
City
Wildomar
State/Province
California
ZIP/Postal Code
92595
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66211
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70114
Country
United States
City
Bloomfield Hills
State/Province
Michigan
ZIP/Postal Code
48302
Country
United States
City
Staten Island
State/Province
New York
ZIP/Postal Code
10312
Country
United States
City
Avon Lake
State/Province
Ohio
ZIP/Postal Code
44012
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19139
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
City
Bothell
State/Province
Washington
ZIP/Postal Code
98011
Country
United States
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 1Z9
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1T8
Country
Canada
City
Whitby
State/Province
Ontario
ZIP/Postal Code
L1N 8M7
Country
Canada
City
Budapest
ZIP/Postal Code
1021
Country
Hungary
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
City
Gyeonggi-do
ZIP/Postal Code
460727
Country
Korea, Republic of
City
Gyeongsang
ZIP/Postal Code
626-770
Country
Korea, Republic of
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
110-769
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
143-729
Country
Korea, Republic of
City
Leon
State/Province
Guanajuato
ZIP/Postal Code
37000
Country
Mexico
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64710
Country
Mexico
City
Durango
ZIP/Postal Code
34000
Country
Mexico
City
Changhua
ZIP/Postal Code
50006
Country
Taiwan
City
Kaohsiung
ZIP/Postal Code
83301
Country
Taiwan
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
City
Taipei
ZIP/Postal Code
114
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://clinical-trials.otsuka.com

Learn more about this trial

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

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