Back to resultsStudy Evaluating the Safety and Efficacy of Fixed-dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
Primary Purpose
Tourette's Disorder, Tic Disorder
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Aripiprazole
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tourette's Disorder focused on measuring Tourette Syndrome, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Tic Disorders, Tics, Movement Disorders, Mental Disorders, Aripiprazole
Eligibility Criteria
Inclusion Criteria:
- male or female, 7 to 17 year old (inclusive) at the time of signing consent
- meets DSM-IV-TR diagnostic criteria for Tourette's Disorder
- Presenting tic symptoms cause impairment in the subject'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 obtained from a legally acceptable representative & informed assent at Screening as applicable by trial center's IRB/IEC
- The subject, 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
- Subject receiving psychostimulants for treatment of 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)
- Taken aripiprazole within 30 days of the Screening visit
- Received any investigational agent in a clinical trial within 30 days prior to Screening, enrolled in studies 31-12-272, 31-12-273, 31-12-274; or who were randomized into a clinical trial with Once-daily aripiprazole at any time
- History of neuroleptic malignant syndrome
- Sexually active patients not using 2 approved methods of contraception
- Females breastfeeding or pregnant (positive blood pregnancy test prior to receiving trial drug)
- Risk of committing suicide
- Body weight lower than 16 kg
- Taken neuroleptic or antiparkinson drugs < 14 days prior to randomization
- Requiring cognitive behavioral therapy (CBT) for Tourette's during trial
- Subject meets DSM-IV-TR criteria for any significant psychoactive substance use disorder within the past 3 months
- Positive drug screen
- Subject 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 trial
- Use of herbal medications of any kind and nutritional or dietary supplements for Tourette's disorder within 7 days prior to dosing and for the duration of the trial
- Inability to swallow tablets or tolerate oral medication
- Abnormal laboratory test results, vital signs and ECG results
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
Aripiprazole 5 mg or 10 mg
Aripiprazole 10 mg or 20 mg
Arm Description
Matching Placebo Once-Daily
Aripiprazole 5 mg or 10 mg Immediate Release Once-Daily
Aripiprazole 10 mg 20 mg Immediate Release Once-Daily
Outcomes
Primary Outcome Measures
Change From Baseline to Week 8 in Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS).
The YGTSS is a semi-structured clinical interview designed to measure current (time frame of the past 1 week) tic severity. This scale consists of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings are 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. Summation of these 10 scores (ie, 0-50) provides a TTS that was the primary outcome measure in this trial. The YGTSS ranking of impairment score rated on a 50-point scale anchored from 0 (no impairment) to 50 (severe impairment) to assess impairment experienced in areas of self-esteem, family life, social acceptance, and school scores. This is a fully validated scale in adults and has become a standard instrument for the evaluation of the severity of TD in children.
Secondary Outcome Measures
Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 8.
To assess CGI-TS severity, the rater or physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" However, the evaluation of illness was limited to manifestations of TD only. 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. The change score was obtained from CGI-TS improvement scale assessment: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Mean Change From Baseline to Endpoint (Week 8) in Total YGTSS Score
The YGTSS consists of a tic inventory, with 5 separate rating scales to rate the severity of symptoms (on a scale of 0 to 5 for 5 different dimensions, including number, frequency, intensity, complexity, and interference) of motor and vocal tics, and an impairment ranking. The Total YGTSS score is the summation of the severity scores of motor and vocal tics and also the ranking of impairment (range of 0 to 100). A missing value of a YGTSS item scale could result in a missing Total YGTSS score. A reduction in Total YGTSS score from baseline represents an improvement in symptoms.
Mean Change From Baseline to Endpoint (Week 8) in CGI-TS Severity Score
The CGI-TS Severity scale (range 0-7) is a single-item rating score, with higher scores representing greater severity or less improvement. A response of 0 (not assessed) is considered and handled as missing data.
Response Rate
Clinical response is defined as > 25% improvement from baseline to Week 8 in YGTSS TTS or a CGI-TS Change score of 1 [very much improved] or 2 [much improved] at Week 8. Response will be considered as missing only if both YGTSS TTS and CGI-TS change score are missing. As long as one of them is non-missing, response outcome will be determined based on the non-missing score.
Treatment Discontinuation Rate
Treatment discontinuation rate will be calculated as the number of discontinued participants (ie, those who were withdrawn from the trial without completing the Week 8 visit) over the number of all randomized participants.
Full Information
NCT ID
NCT01727700
First Posted
November 12, 2012
Last Updated
February 12, 2015
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01727700
Brief Title
Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily 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 Fixed-Dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The goal of the current trial is to determine efficacy and safety of Once-daily aripiprazole in reducing Total Tic Severity in children and adolescents with Tourette's Disorder.
Detailed Description
Tourette's Disorder is a neuropsychiatric condition that is characterized by the appearance of tics that can be simple or complex in nature. A tic is a sudden, rapid, recurrent, non-rhythmic, stereotyped motor movement or vocalization. There are a very limited number of medications approved for the treatment of Tourette's Disorder. The goal of the current trial is to obtain efficacy, safety, and tolerability data in a controlled condition of a Once-daily aripiprazole formulation in children and adolescents with Tourette's Disorder. The trial has an 8-week long double-blind treatment period after a pretreatment (screening/washout phase), and the subjects will be followed up for 1 month after the last treatment. The Once-daily tablet formulation that will be evaluated in this trial represents a daily dosage regimen that is intended to be administered to children and adolescents.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tourette's Disorder, Tic Disorder
Keywords
Tourette Syndrome, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Tic Disorders, Tics, Movement Disorders, Mental Disorders, Aripiprazole
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
133 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo Once-Daily
Arm Title
Aripiprazole 5 mg or 10 mg
Arm Type
Experimental
Arm Description
Aripiprazole 5 mg or 10 mg Immediate Release Once-Daily
Arm Title
Aripiprazole 10 mg or 20 mg
Arm Type
Experimental
Arm Description
Aripiprazole 10 mg 20 mg Immediate Release Once-Daily
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
Abilify
Intervention Description
Once-daily, tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change From Baseline to Week 8 in Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS).
Description
The YGTSS is a semi-structured clinical interview designed to measure current (time frame of the past 1 week) tic severity. This scale consists of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings are 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. Summation of these 10 scores (ie, 0-50) provides a TTS that was the primary outcome measure in this trial. The YGTSS ranking of impairment score rated on a 50-point scale anchored from 0 (no impairment) to 50 (severe impairment) to assess impairment experienced in areas of self-esteem, family life, social acceptance, and school scores. This is a fully validated scale in adults and has become a standard instrument for the evaluation of the severity of TD in children.
Time Frame
Baseline to Week 8
Secondary Outcome Measure Information:
Title
Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 8.
Description
To assess CGI-TS severity, the rater or physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" However, the evaluation of illness was limited to manifestations of TD only. 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. The change score was obtained from CGI-TS improvement scale assessment: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time Frame
Week 8
Title
Mean Change From Baseline to Endpoint (Week 8) in Total YGTSS Score
Description
The YGTSS consists of a tic inventory, with 5 separate rating scales to rate the severity of symptoms (on a scale of 0 to 5 for 5 different dimensions, including number, frequency, intensity, complexity, and interference) of motor and vocal tics, and an impairment ranking. The Total YGTSS score is the summation of the severity scores of motor and vocal tics and also the ranking of impairment (range of 0 to 100). A missing value of a YGTSS item scale could result in a missing Total YGTSS score. A reduction in Total YGTSS score from baseline represents an improvement in symptoms.
Time Frame
Baseline to Week 8
Title
Mean Change From Baseline to Endpoint (Week 8) in CGI-TS Severity Score
Description
The CGI-TS Severity scale (range 0-7) is a single-item rating score, with higher scores representing greater severity or less improvement. A response of 0 (not assessed) is considered and handled as missing data.
Time Frame
Baseline to Week 8
Title
Response Rate
Description
Clinical response is defined as > 25% improvement from baseline to Week 8 in YGTSS TTS or a CGI-TS Change score of 1 [very much improved] or 2 [much improved] at Week 8. Response will be considered as missing only if both YGTSS TTS and CGI-TS change score are missing. As long as one of them is non-missing, response outcome will be determined based on the non-missing score.
Time Frame
Week 8
Title
Treatment Discontinuation Rate
Description
Treatment discontinuation rate will be calculated as the number of discontinued participants (ie, those who were withdrawn from the trial without completing the Week 8 visit) over the number of all randomized participants.
Time Frame
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:
male or female, 7 to 17 year old (inclusive) at the time of signing consent
meets DSM-IV-TR diagnostic criteria for Tourette's Disorder
Presenting tic symptoms cause impairment in the subject'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 obtained from a legally acceptable representative & informed assent at Screening as applicable by trial center's IRB/IEC
The subject, 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
Subject receiving psychostimulants for treatment of 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)
Taken aripiprazole within 30 days of the Screening visit
Received any investigational agent in a clinical trial within 30 days prior to Screening, enrolled in studies 31-12-272, 31-12-273, 31-12-274; or who were randomized into a clinical trial with Once-daily aripiprazole at any time
History of neuroleptic malignant syndrome
Sexually active patients not using 2 approved methods of contraception
Females breastfeeding or pregnant (positive blood pregnancy test prior to receiving trial drug)
Risk of committing suicide
Body weight lower than 16 kg
Taken neuroleptic or antiparkinson drugs < 14 days prior to randomization
Requiring cognitive behavioral therapy (CBT) for Tourette's during trial
Subject meets DSM-IV-TR criteria for any significant psychoactive substance use disorder within the past 3 months
Positive drug screen
Subject 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 trial
Use of herbal medications of any kind and nutritional or dietary supplements for Tourette's disorder within 7 days prior to dosing and for the duration of the trial
Inability to swallow tablets or tolerate oral medication
Abnormal laboratory test results, vital signs and 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:
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12. IPD Sharing Statement
Citations:
PubMed Identifier
28686474
Citation
Sallee F, Kohegyi E, Zhao J, McQuade R, Cox K, Sanchez R, van Beek A, Nyilas M, Carson W, Kurlan R. Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and Safety of Oral Aripiprazole for the Treatment of Tourette's Disorder in Children and Adolescents. J Child Adolesc Psychopharmacol. 2017 Nov;27(9):771-781. doi: 10.1089/cap.2016.0026. Epub 2017 Jul 7.
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Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
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