Back to resultsSafety and Tolerability 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
Sponsored by
About this trial
This is an interventional treatment trial for Tourette's Disorder focused on measuring Tourette's Disorder, Tic Disorders
Eligibility Criteria
Inclusion Criteria:
- The participants successfully completed the final assessment visit in either Study 31-10-272 (NCT01418339) or 31-10-273 (NCT01418352). The participants completed all required assessments for the Week 8/Early Termination Visit to be eligible for rollover in to this open-label trial.
- Written informed consent form (ICF) obtained from a legally acceptable representative & informed assent at Baseline as applicable by trial 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:
- The participants experienced adverse events (AEs) during the double-blind study 31-10-272 (NCT01418339) or 31-10-273 (NCT01418352) that would, in the investigator's judgment, preclude further exposure to aripiprazole.
- The participants had protocol violations during the double-blind trial considered major in the judgment of the investigator which would deem the participant a poor candidate for the trial.
- A positive drug screen at baseline for cocaine, alcohol or other drugs of abuse which will result in early termination at Week 1.
- Sexually active patients who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 90 and 30 days following the last dose of study drug for male and female respectively.
- Participants representing Risk of committing suicide.
- Body weight lower than 16 kg.
- Abnormal laboratory test results (Platelet, Hemoglobin, Neutrophils, Aspartate aminotransferase, Alanine aminotransferase, Creatinine) vital signs and Electrocardiogram (ECG) results.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Aripiprazole
Arm Description
Participants received oral aripiprazole tablets once weekly (QW) with a titrated dose starting from 52.5 milligram (mg), on Day 1 and increasing to 77.5 mg and 110 mg for the remainder of the trial (Up to Week 52), the dose could be adjusted between these 3 dose levels as determined by investigator's discretion based on safety and tolerability.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation
An Adverse Event (AE) is defined as any untoward medical occurrence in a participant enrolled in a clinical trial and which did not necessarily have a causal relationship with the study medication. Treatment emergent adverse events (TEAE) are adverse events occurring after the onset of study drug administration.
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values
The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant lab values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values
Incidence of clinically relevant abnormal ECG values were reported as change from Baseline in heart rate (Tachycardia - ≥15 beats per minute (bpm), Bradycardia ≤15 bpm; Rhythm (Sinus tachycardia ≥15 bpm increase, Sinus bradycardia decrease of ≥15 bpm from Baseline); Presence of - supraventricular premature beat; ventricular premature beat; supraventricular tachycardia; ventricular tachycardia; atrial fibrillation and flutter. Conduction - Presence of primary, secondary or tertiary atrioventricular block, left bundle-branch block, right bundle-branch block, pre-excitation syndrome, other intraventricular conduction blocked QRS ≥0.12 second increase of ≥0.02 second. Acute, subacute or old Infarction, Presence of myocardial ischemia, symmetrical T-wave inversion. Increase in QTc - QTc ≥450 msec ≥10% increase. Any clinically significant change from Baseline assessed by the Investigator are reported.
Number of Participants With Emergence of Suicidal Ideation, TEAEs Related to Suicide and Suicidality and Suicide Ideation From the Potential Suicide Events Recorded on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Suicidal ideation was defined as reporting any type of suicidal ideation. The suicidal ideation intensity total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) which leads to the range of the total score from 0 to 25. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
The AIMS Scale is an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10) are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28. A negative change from Baseline indicates improvement.
Mean Change From Baseline in Body Mass Index (BMI)
The BMI kilogram/meter square (i.e. kg/m^2) was calculated from the Baseline height and the weight at the current visit using one of the following formulae, as appropriate: Weight (kg) divided by [Height (meters)]^2.
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs assessments included orthostatic (supine and standing) blood pressure (BP) measured as millimeter of mercury [mmHg]), heart rate, (measured in beats per minute [bpm]), body weight (measured in kilograms [kg]) and body temperature. Incidence of clinically relevant abnormal values in heart rate, systolic and diastolic blood pressure and weight were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant has been supine for at least 5 minutes and again after the participant has been standing for approximately 2 minutes, but not more than 3 minutes.
Mean Change From Baseline in Simpson Angus Scale (SAS) Score
The SAS is a rating scale used to measure Extrapyramidal symptoms (EPS). The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40. A negative change from Baseline indicates improvement.
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score
The BARS was an EPS rating scale. The BARS was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia). A negative change from Baseline indicates improvement.
Mean Change From Baseline in Average Score of Attention-Deficit Disorder/Attention-Deficit Hyperactivity Disorder (ADD/ADHD) Sub-scale of the Swanson, Nolan and Pelham-IV (SNAP-IV)
The SNAP-IV, ADHD Inattention subscale contains 19 items, items 1 to 9 measure inattention, items 11 to 19 measure hyperactivity/impulsivity, and item 10 for inattention domain that scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 57. The negative change from Baseline indicates improvement.
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score
The CY-BOCS is used to assess characteristics of obsession and compulsion for the week prior to the interview. Nineteen items are rated in the CY-BOCS, but the total score is the sum of only items 1 to 10 (excluding items 1b and 6b). The obsession and compulsion subtotals are the sums of items 1 to 5 (excluding 1b) and 6 to 10 (excluding 6b), respectively. A missing value for any CY-BOCS item scale could result in a missing total score or obsession and compulsion subtotals of which the item scale is a component. At baseline, the full CY-BOCS interview is conducted. At all post-baseline time points, the "Questions on Obsessions" (items 1 to 5) and "Questions on Compulsions" (items 6 to 10) are reviewed and the target symptoms identified at baseline are the primary focus for rating severity. CY-BOCS total score could range from 0 to 40. Higher scores indicate worse outcome. A negative change from Baseline indicates improvement.
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score
The CDRS-R is composed of 17 interviewer-rated symptom areas: impaired schoolwork, difficulty having fun, social withdrawal, appetite disturbance, sleep disturbance, excessive fatigue, physical complaints, irritability, excessive guilt, low self-esteem, depressed feelings, morbid ideas, suicidal ideas, excessive weeping, depressed facial affect, listless speech, and hypoactivity. The CDRS-R total score is the sum of scores for the 17 symptom areas. A missing value for any CDRS-R item scale or a not rated item scale (indicated by the value of 0) could result in a missing total score. The CDRS-R total score is the sum of scores for the 17 symptom areas and could range from 17 to 113 with higher values indicating worse outcome. A negative change from Baseline indicates improvement.
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score
The PARS has 2 sections: the symptom checklist and the severity items. The symptom checklist is used to determine the child's repertoire of symptoms during the past week. Information is elicited from the child and parent(s) and the rater then combines information from all informants using his/her best judgment. The 7-item severity list is used to determine severity of symptoms and the PARS total score. The time frame for the PARS rating is the past week. Only those symptoms endorsed for the past week are included in the symptom checklist and rated on the severity items. The PARS total severity score is the sum of items 2, 3, 5, 6, and 7. The total severity score ranges from 0 to 25, with 25 being the worst. Codes "8" (Not applicable) and "9" (Does not know) are not included in the summation (ie, equivalent to a score of 0 in the summation). A negative change from Baseline indicates improvement.
Mean Change From Baseline in Body Weight
Mean Change From Baseline in Waist Circumference
Waist circumference was recorded before a participant's meal and at approximately the same time at each visit. Measurement was accomplished by locating the upper hip bone and the top of the right iliac crest and placing the measuring tape in a horizontal plane around the abdomen at the level of the crest. Before reading the tape measure, the assessor assured that the tape was snug, but did not compress the skin, and is parallel to the floor. The measurement was made at the end of a normal exhalation.
Secondary Outcome Measures
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score
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 total tic score (TTS) ranged from 0 (none) to 50 (severe) with higher score represent more severe symptoms (A negative change from Baseline indicates improvement).
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness 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 include: 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. A negative change from Baseline indicates improvement.
Mean Change From Baseline 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 negative change in Total YGTSS score from baseline represents an improvement in symptoms.
Response Rates
Response rates - clinical response was defined as percentage of participants >25% improvement from Baseline to endpoint in YGTSS TTS OR a CGI-TS change score of 1 [very much improved] or 2 [much improved] at endpoint. 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) with higher score representing severe symptoms.
Treatment Discontinuation Rates
Treatment discontinuation rate was calculated as the percentage of participants who discontinued treatment.
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall 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.
Full Information
NCT ID
NCT01416441
First Posted
August 1, 2011
Last Updated
September 10, 2021
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01416441
Brief Title
Safety and Tolerability Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
Official Title
An Open-Label, Multicenter Study Evaluating the Safety and Tolerability of 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
October 19, 2011 (Actual)
Primary Completion Date
March 13, 2014 (Actual)
Study Completion Date
March 13, 2014 (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
No
5. Study Description
Brief Summary
The goal of the current trial is to obtain long term efficacy, safety and tolerability data of once weekly aripiprazole 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
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
170 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aripiprazole
Arm Type
Experimental
Arm Description
Participants received oral aripiprazole tablets once weekly (QW) with a titrated dose starting from 52.5 milligram (mg), on Day 1 and increasing to 77.5 mg and 110 mg for the remainder of the trial (Up to Week 52), the dose could be adjusted between these 3 dose levels as determined by investigator's discretion based on safety and tolerability.
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Other Intervention Name(s)
ABILIFY
Intervention Description
Aripiprazole tablets orally once daily.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation
Description
An Adverse Event (AE) is defined as any untoward medical occurrence in a participant enrolled in a clinical trial and which did not necessarily have a causal relationship with the study medication. Treatment emergent adverse events (TEAE) are adverse events occurring after the onset of study drug administration.
Time Frame
From signing of the informed consent up to 30 days after the last dose (Up to Week 52)
Title
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values
Description
The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant lab values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance.
Time Frame
Baseline to Week 52
Title
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values
Description
Incidence of clinically relevant abnormal ECG values were reported as change from Baseline in heart rate (Tachycardia - ≥15 beats per minute (bpm), Bradycardia ≤15 bpm; Rhythm (Sinus tachycardia ≥15 bpm increase, Sinus bradycardia decrease of ≥15 bpm from Baseline); Presence of - supraventricular premature beat; ventricular premature beat; supraventricular tachycardia; ventricular tachycardia; atrial fibrillation and flutter. Conduction - Presence of primary, secondary or tertiary atrioventricular block, left bundle-branch block, right bundle-branch block, pre-excitation syndrome, other intraventricular conduction blocked QRS ≥0.12 second increase of ≥0.02 second. Acute, subacute or old Infarction, Presence of myocardial ischemia, symmetrical T-wave inversion. Increase in QTc - QTc ≥450 msec ≥10% increase. Any clinically significant change from Baseline assessed by the Investigator are reported.
Time Frame
Baseline to Week 52
Title
Number of Participants With Emergence of Suicidal Ideation, TEAEs Related to Suicide and Suicidality and Suicide Ideation From the Potential Suicide Events Recorded on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
Suicidality was defined as reporting at least one occurrence of any suicidal behavior or suicidal ideation. Suicidal behavior was defined as reporting any type of suicidal behaviors (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Suicidal ideation was defined as reporting any type of suicidal ideation. The suicidal ideation intensity total score is the sum of intensity scores of 5 items (frequency, duration, controllability, deterrents, and reasons for ideation). The score of each intensity item ranges from 0 (none) to 5 (worst) which leads to the range of the total score from 0 to 25. A missing score of any item resulted in a missing total score. If no suicidal ideation was reported, a score of 0 was given to the intensity scale.
Time Frame
Baseline to Week 52
Title
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
Description
The AIMS Scale is an extrapyramidal symptoms (EPS) rating scale. The AIMS is a 12 item scale. The first 10 items e.g. facial and oral movements (items 1-4), extremity movements (items 5 and 6), trunk movements (item 7), investigators global assessment of dyskinesia (items 8 to 10) are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28. A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Body Mass Index (BMI)
Description
The BMI kilogram/meter square (i.e. kg/m^2) was calculated from the Baseline height and the weight at the current visit using one of the following formulae, as appropriate: Weight (kg) divided by [Height (meters)]^2.
Time Frame
Baseline and Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)
Title
Number of Participants With Clinically Significant Changes in Vital Signs
Description
Vital signs assessments included orthostatic (supine and standing) blood pressure (BP) measured as millimeter of mercury [mmHg]), heart rate, (measured in beats per minute [bpm]), body weight (measured in kilograms [kg]) and body temperature. Incidence of clinically relevant abnormal values in heart rate, systolic and diastolic blood pressure and weight were identified based on pre-defined criteria. Orthostatic assessments of blood pressure and heart rate were made after the participant has been supine for at least 5 minutes and again after the participant has been standing for approximately 2 minutes, but not more than 3 minutes.
Time Frame
Baseline to Week 52
Title
Mean Change From Baseline in Simpson Angus Scale (SAS) Score
Description
The SAS is a rating scale used to measure Extrapyramidal symptoms (EPS). The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40. A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score
Description
The BARS was an EPS rating scale. The BARS was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia). A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Average Score of Attention-Deficit Disorder/Attention-Deficit Hyperactivity Disorder (ADD/ADHD) Sub-scale of the Swanson, Nolan and Pelham-IV (SNAP-IV)
Description
The SNAP-IV, ADHD Inattention subscale contains 19 items, items 1 to 9 measure inattention, items 11 to 19 measure hyperactivity/impulsivity, and item 10 for inattention domain that scores the intensity of each item during the last seven days on a 0 to 3 scale (0=not at all, 1=just a little, 2=pretty much, 3=very much). The lowest possible score is 0; highest is 57. The negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score
Description
The CY-BOCS is used to assess characteristics of obsession and compulsion for the week prior to the interview. Nineteen items are rated in the CY-BOCS, but the total score is the sum of only items 1 to 10 (excluding items 1b and 6b). The obsession and compulsion subtotals are the sums of items 1 to 5 (excluding 1b) and 6 to 10 (excluding 6b), respectively. A missing value for any CY-BOCS item scale could result in a missing total score or obsession and compulsion subtotals of which the item scale is a component. At baseline, the full CY-BOCS interview is conducted. At all post-baseline time points, the "Questions on Obsessions" (items 1 to 5) and "Questions on Compulsions" (items 6 to 10) are reviewed and the target symptoms identified at baseline are the primary focus for rating severity. CY-BOCS total score could range from 0 to 40. Higher scores indicate worse outcome. A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score
Description
The CDRS-R is composed of 17 interviewer-rated symptom areas: impaired schoolwork, difficulty having fun, social withdrawal, appetite disturbance, sleep disturbance, excessive fatigue, physical complaints, irritability, excessive guilt, low self-esteem, depressed feelings, morbid ideas, suicidal ideas, excessive weeping, depressed facial affect, listless speech, and hypoactivity. The CDRS-R total score is the sum of scores for the 17 symptom areas. A missing value for any CDRS-R item scale or a not rated item scale (indicated by the value of 0) could result in a missing total score. The CDRS-R total score is the sum of scores for the 17 symptom areas and could range from 17 to 113 with higher values indicating worse outcome. A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score
Description
The PARS has 2 sections: the symptom checklist and the severity items. The symptom checklist is used to determine the child's repertoire of symptoms during the past week. Information is elicited from the child and parent(s) and the rater then combines information from all informants using his/her best judgment. The 7-item severity list is used to determine severity of symptoms and the PARS total score. The time frame for the PARS rating is the past week. Only those symptoms endorsed for the past week are included in the symptom checklist and rated on the severity items. The PARS total severity score is the sum of items 2, 3, 5, 6, and 7. The total severity score ranges from 0 to 25, with 25 being the worst. Codes "8" (Not applicable) and "9" (Does not know) are not included in the summation (ie, equivalent to a score of 0 in the summation). A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Body Weight
Time Frame
Baseline to Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Waist Circumference
Description
Waist circumference was recorded before a participant's meal and at approximately the same time at each visit. Measurement was accomplished by locating the upper hip bone and the top of the right iliac crest and placing the measuring tape in a horizontal plane around the abdomen at the level of the crest. Before reading the tape measure, the assessor assured that the tape was snug, but did not compress the skin, and is parallel to the floor. The measurement was made at the end of a normal exhalation.
Time Frame
Baseline to Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score
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 total tic score (TTS) ranged from 0 (none) to 50 (severe) with higher score represent more severe symptoms (A negative change from Baseline indicates improvement).
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness 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 include: 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. A negative change from Baseline indicates improvement.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Mean Change From Baseline 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 negative change in Total YGTSS score from baseline represents an improvement in symptoms.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Response Rates
Description
Response rates - clinical response was defined as percentage of participants >25% improvement from Baseline to endpoint in YGTSS TTS OR a CGI-TS change score of 1 [very much improved] or 2 [much improved] at endpoint. 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) with higher score representing severe symptoms.
Time Frame
Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)
Title
Treatment Discontinuation Rates
Description
Treatment discontinuation rate was calculated as the percentage of participants who discontinued treatment.
Time Frame
Up to Week 53
Title
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall 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.
Time Frame
Baseline and Weeks 4, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The participants successfully completed the final assessment visit in either Study 31-10-272 (NCT01418339) or 31-10-273 (NCT01418352). The participants completed all required assessments for the Week 8/Early Termination Visit to be eligible for rollover in to this open-label trial.
Written informed consent form (ICF) obtained from a legally acceptable representative & informed assent at Baseline as applicable by trial 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:
The participants experienced adverse events (AEs) during the double-blind study 31-10-272 (NCT01418339) or 31-10-273 (NCT01418352) that would, in the investigator's judgment, preclude further exposure to aripiprazole.
The participants had protocol violations during the double-blind trial considered major in the judgment of the investigator which would deem the participant a poor candidate for the trial.
A positive drug screen at baseline for cocaine, alcohol or other drugs of abuse which will result in early termination at Week 1.
Sexually active patients who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 90 and 30 days following the last dose of study drug for male and female respectively.
Participants representing Risk of committing suicide.
Body weight lower than 16 kg.
Abnormal laboratory test results (Platelet, Hemoglobin, Neutrophils, Aspartate aminotransferase, Alanine aminotransferase, Creatinine) 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
Dothan
State/Province
Alabama
ZIP/Postal Code
36303
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95815
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
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
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33126
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
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5200
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
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
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
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
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
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
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
84106
Country
United States
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
City
Bothell
State/Province
Washington
ZIP/Postal Code
98011
Country
United States
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
City
Ruse
ZIP/Postal Code
7004
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
City
Calgary
ZIP/Postal Code
T3B 6A8
Country
Canada
City
Kelowna
ZIP/Postal Code
V1Y 1Z9
Country
Canada
City
Toronto
ZIP/Postal Code
M5B 1T9
Country
Canada
City
Toronto
ZIP/Postal Code
M5T 2S8
Country
Canada
City
Whitby
ZIP/Postal Code
L1N 8M7
Country
Canada
City
Aachen
ZIP/Postal Code
52074
Country
Germany
City
Dresden
ZIP/Postal Code
1307
Country
Germany
City
Hannover
ZIP/Postal Code
30625
Country
Germany
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
City
Ulm
ZIP/Postal Code
89075
Country
Germany
City
Budapest
ZIP/Postal Code
1021
Country
Hungary
City
Szeged
ZIP/Postal Code
6725
Country
Hungary
City
Gyeonggi-do
ZIP/Postal Code
420-767
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
110-744
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
Culiacán
ZIP/Postal Code
80020
Country
Mexico
City
Delegación Miguel Hidalgo
ZIP/Postal Code
11000
Country
Mexico
City
Durango
ZIP/Postal Code
34000
Country
Mexico
City
Leon
ZIP/Postal Code
37000
Country
Mexico
City
Monterrey
ZIP/Postal Code
64710
Country
Mexico
City
Bucuresti
ZIP/Postal Code
41915
Country
Romania
City
Cluj-Napoca
ZIP/Postal Code
400660
Country
Romania
City
Craiova
ZIP/Postal Code
200620
Country
Romania
City
Iasi
ZIP/Postal Code
700265
Country
Romania
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
City
Donetsk
ZIP/Postal Code
83008
Country
Ukraine
City
Kharkiv
ZIP/Postal Code
61068
Country
Ukraine
City
Kharkiv
ZIP/Postal Code
61153
Country
Ukraine
City
Kyiv
ZIP/Postal Code
03049
Country
Ukraine
City
Kyiv
ZIP/Postal Code
4209
Country
Ukraine
City
Lugansk
ZIP/Postal Code
91045
Country
Ukraine
City
Poltava
ZIP/Postal Code
36006
Country
Ukraine
City
Stepanivka
ZIP/Postal Code
73488
Country
Ukraine
City
Vinnytsia
ZIP/Postal Code
21005
Country
Ukraine
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
Safety and Tolerability Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
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