Trial Outcomes & Findings for Safety and Tolerability Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder (NCT NCT01416441)

NCT ID: NCT01416441

Last Updated: 2021-10-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 170 participants
• Primary outcome timeframe: From signing of the informed consent up to 30 days after the last dose (Up to Week 52)
• Results posted on: 2021-10-07

Participant Flow

A total of 170 participants were screened and enrolled. 114 participants were enrolled from study 31-10-272 (NCT01418339) and 56 participants were enrolled from study 31-10-273 (NCT01418352). The participants were recruited at 79 sites in following 10 countries: Bulgaria, Canada, Germany, Hungary, Mexico, Romania, South Korea, Taiwan, Ukraine and the US from 19 October 2011 to 13 March 2014.

Children and adolescents with Tourette's disorder who had successfully completed the previous studies, entered this 52-week open-label extension study to receive once-weekly aripiprazole tablet.

Participant milestones

Measure	Aripiprazole (Once Weekly) 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.
Overall Study STARTED	170
Overall Study COMPLETED	89
Overall Study NOT COMPLETED	81

Reasons for withdrawal

Measure	Aripiprazole (Once Weekly) 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.
Overall Study Lost to Follow-up	5
Overall Study Adverse Event	6
Overall Study Sponsor Discontinued Trial Site	43
Overall Study Subject Met Withdrawal Criteria	10
Overall Study Investigator Withdrew Subject	2
Overall Study Subject Withdrew Consent	12
Overall Study Lack of Efficacy as Determined by the Investigator	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Age, Continuous	12.2 years STANDARD_DEVIATION 2.9 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	136 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	36 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants
Race (NIH/OMB) White	117 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment Canada	19 participants n=5 Participants
Region of Enrollment South Korea	15 participants n=5 Participants
Region of Enrollment Romania	8 participants n=5 Participants
Region of Enrollment Hungary	14 participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants
Region of Enrollment Taiwan	21 participants n=5 Participants
Region of Enrollment Ukraine	21 participants n=5 Participants
Region of Enrollment Mexico	14 participants n=5 Participants
Region of Enrollment Bulgaria	5 participants n=5 Participants
Region of Enrollment Germany	3 participants n=5 Participants
Weight	51.5 Kilogram STANDARD_DEVIATION 19 • n=5 Participants
Height	154.2 centimeter STANDARD_DEVIATION 16.4 • n=5 Participants
Body Mass Index (BMI)	21.0 Kilogram per meter square STANDARD_DEVIATION 4.7 • n=5 Participants
Time since first diagnosis for Tourette's Disorder	2.3 Years STANDARD_DEVIATION 2.5 • n=5 Participants

PRIMARY outcome

Timeframe: From signing of the informed consent up to 30 days after the last dose (Up to Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation Participants with Serious TEAEs	5 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation Participants with Severe TEAEs	8 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation Participants Discontinued Medication due to TEAE's	6 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs and TEAEs Leading Treatment Discontinuation Participants with TEAEs	104 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses of the specific category.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Alanine Aminotransferase	1 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-HDL Cholesterol, Fasting	3 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Lactic Dehydrogenase	1 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-LDL-Cholesterol, Fasting	2 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Sodium	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Uric Acid	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Urinalysis-Glucose, Urine	3 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Haematology-Neutrophils	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Haematology-Platelet Count	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Haematology-White Blood Count	4 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Alkaline Phosphatase	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Aspartate Aminotransferase	1 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Bilirubin, Total	4 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Calcium	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Chloride	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Creatine Phosphokinase	4 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Creatinine	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Glucose	1 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Glucose, Fasting	1 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry-Potassium	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry- Triglycerides, Fasting	19 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Chemistry- Urea Nitrogen	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Urinalysis-Protein, Urine	1 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Other-Prolactin	3 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Haematology-Eosinophils	3 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Haematology-Hematocrit	0 Participants
Number of Participants With Clinically Significant Changes in Laboratory Parameter Values Haematology-Hemoglobin	3 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study, with data available for analyses.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=154 Participants 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.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Bradycardia	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Sinus Bradycardia	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Old Infarction	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values QT Interval Corrected for Heart Rate by the US Food and Drug (QTcN)	1 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Tachycardia	1 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Sinus Tachycardia	1 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Supraventricular Premature Beat	4 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Ventricular Premature Beat	3 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Supraventricular Tachycardia	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Ventricular Tachycardia	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Atrial Fibrillation	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Atrial Flutter	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Primary Atrioventricular Block	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Secondary Atrioventricular Block	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Tertiary Atrioventricular Block	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Left Bundle Branch Block	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Right Bundle Branch Block	2 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Pre-excitation Syndrome	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Other intraventricular conduction block	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Acute or Sub-acute Infarction	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Myocardial Ischemia	0 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values Symmetrical T-Wave Inversion	1 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values QT Interval cCorrected for Heart Rate by Bazett's Formula (QTB)	3 participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values QT Interval Corrected for Heart Rate by Fredericia's Formula (QTcF)	0 participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses of the specific category.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
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) Emergence of Suicidal Ideation	3 Participants
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) TEAEs related to Suicide	3 Participants
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 and Suicidal Ideation	4 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 16	-0.5 score on a scale Standard Deviation 2
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 20	-0.5 score on a scale Standard Deviation 2
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 24	-0.6 score on a scale Standard Deviation 2.5
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 32	-0.8 score on a scale Standard Deviation 2.3
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 40	-0.8 score on a scale Standard Deviation 2.4
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 52	-0.9 score on a scale Standard Deviation 2.4
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 4	-0.1 score on a scale Standard Deviation 1.3
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 8	-0.1 score on a scale Standard Deviation 1.6
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Week 12	-0.4 score on a scale Standard Deviation 1.7
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score Change at Last Visit (Early Termination Visit Prior to or at Week 52	-0.8 score on a scale Standard Deviation 2.3

PRIMARY outcome

Timeframe: Baseline and Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Body Mass Index (BMI) Change at Week 12	0.6 kg/m^2 Standard Deviation 0.9
Mean Change From Baseline in Body Mass Index (BMI) Change at Week 24	0.4 kg/m^2 Standard Deviation 1.5
Mean Change From Baseline in Body Mass Index (BMI) Change at Week 52	0.7 kg/m^2 Standard Deviation 2
Mean Change From Baseline in Body Mass Index (BMI) Change at Last Visit (Early Termination Visit Prior to or at Week 52	0.6 kg/m^2 Standard Deviation 1.8

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses of the specific category at given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Number of Participants With Clinically Significant Changes in Vital Signs Heart Rate Standing-increase ≥15 bpm	4 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Systolic Supine BP- Decrease ≥20 mmHg	1 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Systolic Supine BP- Increase ≥20 mmHg	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Systolic Standing BP- Increase ≥20 mmHg	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Systolic Standing BP- Decrease ≥20 mmHg	1 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Diastolic Supine BP- Increase ≥15 mmHg	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Diastolic Supine BP- Decrease ≥15 mmHg	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Diastolic Standing BP- Increase ≥15 mmHg	1 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Weight-Loss ≥ 7%	6 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Heart Rate Supine- Increase ≥15 bpm	1 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Heart Rate Supine- Decrease ≥15 bpm	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Heart Rate Standing- Decrease ≥15 bpm	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Diastolic Standing BP- Decrease ≥15 mmHg	0 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Orthostatic Hypotension	2 Participants
Number of Participants With Clinically Significant Changes in Vital Signs Weight-Gain ≥ 7%	82 Participants

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 4	0 score on scale Standard Deviation 0.3
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 8	0 score on scale Standard Deviation 0.4
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 12	0 score on scale Standard Deviation 0.3
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 20	0 score on scale Standard Deviation 0.2
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 16	0 score on scale Standard Deviation 0.4
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 24	0 score on scale Standard Deviation 0.5
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 32	0 score on scale Standard Deviation 0.4
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 40	0 score on scale Standard Deviation 0.5
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Week 52	0 score on scale Standard Deviation 0.5
Mean Change From Baseline in Simpson Angus Scale (SAS) Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	0 score on scale Standard Deviation 0.4

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	0 score on a scale Standard Deviation 0.3
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 4	0 score on a scale Standard Deviation 0.3
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 8	0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 12	0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 16	0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 20	0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 24	0 score on a scale Standard Deviation 0.1
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 32	0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 40	0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Score Change at Week 52	0 score on a scale Standard Deviation 0.3

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
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) Change at Week 4	-0.1 score on a scale Standard Deviation 0.3
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) Change at Last Visit (Week 52 or early termination Visit before Week 52)	-0.1 score on a scale Standard Deviation 0.4
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) Change at Week 8	0 score on a scale Standard Deviation 0.3
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) Change at Week 12	-0.1 score on a scale Standard Deviation 0.3
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) Change at Week 16	-0.1 score on a scale Standard Deviation 0.4
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) Change at Week 20	-0.1 score on a scale Standard Deviation 0.3
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) Change at Week 24	-0.2 score on a scale Standard Deviation 0.4
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) Change at Week 32	-0.2 score on a scale Standard Deviation 0.4
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) Change at Week 40	-0.2 score on a scale Standard Deviation 0.4
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) Change at Week 52	-0.1 score on a scale Standard Deviation 0.4

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 4	-0.2 score on a scale Standard Deviation 1.6
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 8	-0.2 score on a scale Standard Deviation 1.9
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 12	-0.3 score on a scale Standard Deviation 1.8
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 16	-0.4 score on a scale Standard Deviation 1.9
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 20	-0.4 score on a scale Standard Deviation 2
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 24	-0.5 score on a scale Standard Deviation 2.2
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 32	-0.6 score on a scale Standard Deviation 2.5
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 40	-0.6 score on a scale Standard Deviation 2.4
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Week 52	-0.3 score on a scale Standard Deviation 2.4
Mean Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	-0.3 score on a scale Standard Deviation 2.4

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 8	0 score on a scale Standard Deviation 2.6
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 32	-0.1 score on a scale Standard Deviation 2.8
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 4	0 score on a scale Standard Deviation 2.3
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 12	-0.2 score on a scale Standard Deviation 3.1
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 16	-0.4 score on a scale Standard Deviation 2.9
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 20	-0.3 score on a scale Standard Deviation 3.1
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 24	-0.2 score on a scale Standard Deviation 2.5
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 40	-0.4 score on a scale Standard Deviation 2.7
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Week 52	-0.2 score on a scale Standard Deviation 3.3
Mean Change From Baseline in Children's Depression Rating Scale Revised (CDRS-R) Total Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	0.3 score on a scale Standard Deviation 4.1

PRIMARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 40	-0.6 score on a scale Standard Deviation 2.3
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 4	-0.1 score on a scale Standard Deviation 2.6
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 8	-0.2 score on a scale Standard Deviation 2.4
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 12	-0.3 score on a scale Standard Deviation 1.8
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 16	-0.3 score on a scale Standard Deviation 2
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 20	-0.3 score on a scale Standard Deviation 2.1
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 24	-0.3 score on a scale Standard Deviation 2.3
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 32	-0.3 score on a scale Standard Deviation 2.4
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Week 52	-0.7 score on a scale Standard Deviation 2.4
Mean Change From Baseline in Pediatric Anxiety Rating Scale (PARS) Total Severity Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	-0.3 score on a scale Standard Deviation 2.6

PRIMARY outcome

Timeframe: Baseline to Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Body Weight Change at Week 12	1.4 kilogram Standard Deviation 2.3
Mean Change From Baseline in Body Weight Change at Week 24	2.5 kilogram Standard Deviation 3.9
Mean Change From Baseline in Body Weight Change at Week 52	4.7 kilogram Standard Deviation 6
Mean Change From Baseline in Body Weight Change at Last Visit (Week 52 or early termination Visit before Week 52)	3.8 kilogram Standard Deviation 5.1

PRIMARY outcome

Timeframe: Baseline to Weeks 12, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Waist Circumference Change at Week 24	1 centimeter Standard Deviation 5.2
Mean Change From Baseline in Waist Circumference Change at Week 52	2.3 centimeter Standard Deviation 6.8
Mean Change From Baseline in Waist Circumference Change at Week 12	0.4 centimeter Standard Deviation 3.9
Mean Change From Baseline in Waist Circumference Change at Last Visit (Week 52 or early termination Visit before Week 52)	1.9 centimeter Standard Deviation 5.8

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for analyses at the given timepoint.

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).

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 4	-2.6 score on scale Standard Deviation 5.4
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 16	-4.6 score on scale Standard Deviation 6.8
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 20	-5.5 score on scale Standard Deviation 7.2
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 40	-6.4 score on scale Standard Deviation 9.3
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	-5.9 score on scale Standard Deviation 8.4
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 8	-3.8 score on scale Standard Deviation 5.6
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 12	-4.5 score on scale Standard Deviation 6.7
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 24	-5.8 score on scale Standard Deviation 7.9
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 32	-6 score on scale Standard Deviation 9.1
Mean Change From Baseline in Yale Global Tic Severity Scale (YGTSS) Total Tic Score Change at Week 52	-5.8 score on scale Standard Deviation 8.8

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Efficacy Sample included all participants who received at least one dose of open-label study medication in this study and had a baseline and at least one post baseline efficacy evaluation. Number analyzed is the number of participants with data available for the analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 32	-0.6 score on a scale Standard Deviation 1
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 8	-0.4 score on a scale Standard Deviation 0.8
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 16	-0.5 score on a scale Standard Deviation 0.8
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 24	-0.5 score on a scale Standard Deviation 0.9
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 4	-0.2 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 12	-0.4 score on a scale Standard Deviation 0.8
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 20	-0.6 score on a scale Standard Deviation 0.8
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 40	-0.7 score on a scale Standard Deviation 1.1
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Week 52	-0.7 score on a scale Standard Deviation 1.1
Mean Change From Baseline in Clinical Global Impression for Tourette's Syndrome (CGI-TS) Severity of Illness Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	-0.6 score on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Safety Sample included all participants who received at least one dose of open-label study medication in this study. Number analyzed is the number of participants with data available for the analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Total YGTSS Score Change at Week 32	-11.6 score on a scale Standard Deviation 17.5
Mean Change From Baseline in Total YGTSS Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	-11.4 score on a scale Standard Deviation 16.7
Mean Change From Baseline in Total YGTSS Score Change at Week 4	-5.6 score on a scale Standard Deviation 10.4
Mean Change From Baseline in Total YGTSS Score Change at Week 8	-7.4 score on a scale Standard Deviation 11.8
Mean Change From Baseline in Total YGTSS Score Change at Week 12	-8.6 score on a scale Standard Deviation 12.9
Mean Change From Baseline in Total YGTSS Score Change at Week 16	-9.4 score on a scale Standard Deviation 13.9
Mean Change From Baseline in Total YGTSS Score Change at Week 20	-10.7 score on a scale Standard Deviation 14.9
Mean Change From Baseline in Total YGTSS Score Change at Week 24	-10.4 score on a scale Standard Deviation 16
Mean Change From Baseline in Total YGTSS Score Change at Week 40	-12.6 score on a scale Standard Deviation 17.5
Mean Change From Baseline in Total YGTSS Score Change at Week 52	-10.8 score on a scale Standard Deviation 17.4

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32,40, 52; Last Visit (Week 52 or early termination Visit before Week 52)

Population: Efficacy Sample included all participants who received at least one dose of open-label study medication in this study and had a baseline and at least one post baseline efficacy evaluation. Number analyzed is the number of participants with data available for the analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Response Rates Week 4	66.2 percentage of participants
Response Rates Week 32	77.8 percentage of participants
Response Rates Week 40	80.8 percentage of participants
Response Rates Week 8	69.7 percentage of participants
Response Rates Week 12	72.6 percentage of participants
Response Rates Week 16	72.3 percentage of participants
Response Rates Week 20	74.2 percentage of participants
Response Rates Week 24	71.8 percentage of participants
Response Rates Week 52	76.5 percentage of participants
Response Rates Last Visit (Week 52 or early termination Visit before Week 52)	71.3 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 53

Population: Enrolled Sample include all participants who met the entrance criteria and enrolled in the trial.

Treatment discontinuation rate was calculated as the percentage of participants who discontinued treatment.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Treatment Discontinuation Rates All reasons	47.6 percentage of participants
Treatment Discontinuation Rates Other than sponsor discontinued study site	22.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 24, 52 and Last Visit (Week 52 or early termination Visit before Week 52)

Population: Efficacy Sample included all participants who received at least one dose of open-label study medication in this study and had a baseline and at least one post baseline efficacy evaluation. Number analyzed is the number of participants with data available for the analyses at the given timepoint.

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.

Outcome measures

Measure	Aripiprazole (Once Weekly) n=170 Participants 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.
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall Score Change at Last Visit (Week 52 or early termination Visit before Week 52)	-3.8 score on a scale Standard Deviation 10.9
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall Score Change at Week 4	-2.9 score on a scale Standard Deviation 8.2
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall Score Change at Week 24	-3.6 score on a scale Standard Deviation 11.3
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall Score Change at Week 52	-4.3 score on a scale Standard Deviation 10.5

Adverse Events

Aripiprazole (Once Weekly)

Serious events: 5 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aripiprazole (Once Weekly) n=170 participants at risk 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.
Investigations Blood creatinine phosphokinase increased	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Investigations Blood lactate dehydrogenase increased	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Investigations Alanine aminotransferase increased	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Investigations Aspartate aminotransferase increased	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Congenital, familial and genetic disorders Tourette's disorder	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Nervous system disorders Tremor	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Psychiatric disorders Suicidal ideation	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Infections and infestations Appendicitis	0.59% 1/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)

Other adverse events

Measure	Aripiprazole (Once Weekly) n=170 participants at risk 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.
Investigations Weight increased	8.2% 14/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Nervous system disorders Headache	11.2% 19/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Nervous system disorders Somnolence	6.5% 11/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Gastrointestinal disorders Nausea	5.9% 10/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Gastrointestinal disorders Vomiting	7.1% 12/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Infections and infestations Nasopharyngitis	7.1% 12/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)
Infections and infestations Upper respiratory tract infection	7.1% 12/170 • From first dose up to 4 weeks post last dose (Up to 56 weeks)

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: clinicaltransparency@otsuka-us.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
• Publication restrictions are in place

Restriction type: OTHER