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

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01727713
• Collaborator: (none)
• Enrollment: 110
• Locations: 33
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The goal of the current trial is to determine safety of Once-daily aripiprazole in reducing Total Tic Severity in children and adolescents with Tourette's Disorder.

Condition or Disease	Intervention/Treatment	Phase
Tourette's Disorder; Tic Disorder	Drug: Aripiprazole	Phase 3

Detailed Description

Tourette's Disorder is a neuropsychiatric condition that is characterized by the appearance of tics that can be simple or complex in nature. A tic is a sudden, rapid, recurrent, non-rhythmic, stereotyped motor movement or vocalization. There are a very limited number of medications approved for the treatment of Tourette's Disorder. The goal of the current trial is to obtain additional efficacy, safety, and tolerability data in a controlled condition of a Once-daily aripiprazole formulation in children and adolescents with Tourette's Disorder. The trial is a 52-week extension to the double-blind trial.

The Once-daily tablet formulation that will be evaluated in this trial represents a daily dosage regimen that is intended to be administered to children and adolescents.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study Evaluating the Safety and Tolerability of Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole Aripiprazole Immediate Release Once-Daily	Drug: Aripiprazole; Open Label: Once-Daily formulation of aripiprazole flex dose regimine; Other Names: Abilify

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events. [Baseline, throighout the 52-week treatmetn and 30±3 days after last trial visit]

   An AE is defined as any untoward medical occurrence in a patient or participant enrolled in the clinical trial and which does not necessarily have to have a causal relationship with the study drug. A treatment emergent adverse event (TEAE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to have a causal relationship with the study drug. Serious adverse event (SAE) or reaction is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolonged hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.

2. Percentage of Participants With Clinically Significant Abnormal Laboratory Test Results. [Baseline to Week 52]

   Laboratory tests including hematology, serum chemistry, and urinalysis were performed for all the participants. The central laboratory was used for all laboratory testing whenever possible. Any value outside the normal range was flagged for the attention of the study physician who was to indicate whether the value was clinically significant based on the pre-defined criteria for identifying laboratory values of potential clinical relevance. Percentage of participants noted with abnormal laboratory values are reported below.

3. Percentage of Participants With Clinically Significant Abnormal Vital Signs. [Baseline to Week 52]

   Vital sign measurements included systolic and diastolic blood pressure (BP) and heart rate, which were performed at all clinic visits. Criteria for identifying vital signs of potential clinical relevance included: Heart rate: ≥ 15 beats per minute (bpm) increase/decrease from Baseline (final visit of study 31-12-293); Systolic BP: ≥ 20 mmHg increase/decrease from Baseline; Diastolic BP: ≥ 15mmHg increase/decrease from Baseline; Orthostatic hypotension: ≥ 20 mmHg decrease in systolic BP and a ≥ 25 bpm increase in heart rate from supine to sitting/standing. Percentage of participants noted with abnormal vital sign measurements are reported below.

4. Percentage of Participants With Clinically Significant Abnormal Electrocardiogram (ECG). [Baseline to Week 52]

   Three 12-lead ECGs (scheduled 5 minutes apart) were recorded. Some of the pre-defined criteria for identifying ECG measurements of potential clinical relevance included: Tachycardia/sinus tachycardia: increase of ≥15 bpm from Baseline; increase in QTc of ≥10% from Baseline. The other abnormalities not present at Baseline and were present during the time of measurement were recorded. Percentage of participants noted with abnormal ECG findings are reported below.

5. Mean Change From Baseline in Body Weight. [Baseline to Weeks 12, 28, 36, 44, 52/Last visit.]

   Criteria for identifying weight of potential clinical relevance was: ≥ 7% kilogram increase/decrease from Baseline (Final visit of Trial 31-12-293).

6. Mean Change From Baseline in Body Mass Index (BMI). [Baseline to Weeks 28, 52 and Last visit.]

   BMI was calculated at the Baseline visit (using the Baseline height from study 31-12-293) and at Weeks 28 and 52/ET where height measured at baseline in the current trial was used to calculate BMI.

7. Mean Change From Baseline in Waist Circumference. [Baseline to Weeks 12, 28, 36, 44, and 52/last visit.]

   Waist circumference was measured at Baseline, Weeks 12, 28, 36, 44, and the Week 52/last visit in centimeters.

8. Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score. [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

   The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) were observed unobtrusively while the participant was at rest, and the investigator also made global judgments on the participant's dyskinesias (items 8 through 10). Each item was rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness/severe distress). In addition, the AIMS included 2 yes/no questions that addressed the subject's dental status (since an edentulous state can cause lingual dyskinesias). The AIMS movement rating score (range 0 to 28) was the sum of the rating scores for facial and oral moments (ie, items 1 to 4), extremity movements (ie, items 5 and 6), and trunk movements (ie, item 7).

9. Change From Baseline in Simpson-Angus Scale (SAS) Total Score. [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

   The SAS 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). Each item was rated on a 5-point scale, with a score of 1 representing absence of symptoms, and a score of 5 representing a severe condition. The SAS total score (range 10 to 50) was the sum of the rating scores for 10 items from the SAS panel.

10. Change From Baseline in Barnes Akathisia Rating Scale (BARS) Total Score. [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

    The BARS Global Score is derived from the global clinical evaluation of akathisia on a 6-point scale, with 0 representing absence of symptoms and a score of 5 representing severe akathisia.

11. Change From Baseline in Suicidal Ideation Intensity Total Score Based on Columbia-Suicide Severity Rating Scale (C-SSRS). [Baseline, Weeks 1, 2, 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

    The C-SSRS consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post baseline/"since last visit" evaluation that focuses on suicidality since the last trial visit. The C-SSRS data at Baseline and post baseline were summarized for incidence of reporting: Suicidality, Suicidal behavior (and its 4 types), Suicidal ideation (and its 5 types). The intensity score of each item ranges from 1 (least severe) to 5 (most severe), which leads to the range of the total score from 0 to 25.

12. Change From Baseline in Average Score of Attention Deficit Disorder/Attention-deficit Hyperactivity Disorder (ADD/ADHD) of Swanson, Nolan, and Pelham-IV Rating Scale (SNAP-IV). [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

    The SNAP-IV Rating Scale is a revision of the SNAP Questionnaire. The SNAP-IV assesses inattention and hyperactivity/impulsivity, as well as oppositional defiant disorder that are often present in children with ADD/ADHD. The SNAP-IV was administered as a semi-structured interview with the participant and caregiver. The SNAP-IV is based on a 0 to 3 rating scale: not at all = 0, just a little = 1, quite a bit = 2, and very much = 3. The ADD/ADHD subscale includes items 1 through 19 (items 1-9 measure inattention, items 11-19 measure hyperactivity/ impulsivity, and item 10 for inattention domain), items 4, 8, 11, 31, and 32 measure inattention/overactivity, and items 21, 23, 29, 34, and 35 measure aggression/defiance. Items 4, 8, 11, 21, 32, 33, 36, 37, 38, and 39 form the Conners Index. Subscale average scores on the SNAP IV were calculated by summing the scores on the items in the subset and dividing by the number of items in the subset.

13. Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

    The CY-BOCS is a semi-structured interview used with children and adolescents aged 6 to 17 years to rate the severity and type of symptoms in participants with obsessive compulsive disorder. In general, the items depend on the participant's report; however, the final rating is based on the clinical judgment of the interviewer and should include additional information supplied by others. Nineteen items are rated in the CY-BOCS, but only items 1 through 10 (excluding items lb and 6b) are used to determine the total score. The total CY-BOCS score is the sum of items 1 through 10 (excluding lb and 6b), whereas the obsession and compulsion subtotals are the sums of items 1 through 5 (excluding lb) and 6 through 10 (excluding 6b), respectively. CY-BOCS total score could range from 0 to 40, and the obsession and compulsion subscale total scores could each range from 0 to 20. Higher scores indicate worse outcome.

14. Change From Baseline in Children's Depression Rating Scale - Revised (CDRS-R). [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

    The CDRS-R is a brief rating scale based on a semi-structured interview with the child and an adult informant who knows the child well. Designed for 6- to 12-year-old children, and successfully used with adolescents, it can be administered in 15 to 20 minutes. The interviewer rates 17 symptom areas (including those that serve as Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for a diagnosis of depression): 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 and could range from 17 to 113 with higher values indicating worse outcome.

15. Change From Baseline in Pediatric Anxiety Rating Scale (PARS). [Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit]

    The PARS is used to rate the severity of anxiety in children and adolescents, aged 6 to 17 years. 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. The 7-item severity list is used to determine severity of symptoms and the PARS total score. The time frame for the PARS 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 was the sum of items 2, 3, 5, 6, and 7. The total severity score ranged from 0 (no anxiety) to 25 (worst anxiety).

Secondary Outcome Measures

1. Change From Baseline to Endpoint on the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS). [Baseline to Week 52]

   The YGTSS is a semi-structured clinical interview which consists of a tic inventory, with 5 separate ratings to assess the number, intensity, frequency, complexity and interference of tics, plus an overall impairment/disability score. Ratings are made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics each, including number, frequency, intensity, complexity, and interference. Summation of these 10 scores (ie, 0-50) provides a TTS that was the secondary outcome measure in this trial. The YGTSS ranking of impairment, with a maximum of 50 points, is based on the impact of the tic disorder on areas of self-esteem, family life, social acceptance, and school scores. The total severity score ranged from 0 (no impairment) to 50 (worst impairment).

2. Mean Clinical Global Impressions for Tourette's Syndrome (CGI-TS) Change Score at Endpoint. [Baseline to Week 52]

   The CGI is a 7-point Likert scale used in a multitude of clinical trials as a clinical global measure to assess the severity and change in disease symptomatology (ie, tics). The CGI was included as a secondary scale to provide a more complete assessment of clinical efficacy. To assess CGI-TS severity, the rater or investigator will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" However, the evaluation of illness will be limited to manifestations of Tourette's Disorder only. Response choices include: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients.

3. Change From Baseline to Endpoint in CGI-TS Severity of Illness Score. [Baseline to Week 52]

   The final CGI-TS score was compared to the participant's baseline condition at the time of entry into the open-label study, rather than the CGI-TS baseline condition at the time participants enrolled into the preceding study. 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.

4. Mean Change From Baseline to Endpoint in Total YGTSS Score. [Baseline to Week 52]

   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) for motor and vocal tics, and an impairment ranking. The YGTSS TTS is the summation of the severity scores of motor and vocal tics (range of 0 [no impairment] to 50 [maximum impairment]). The total YGTSS score is the summation of the severity scores of motor and vocal tics and the ranking of impairment (total range of 0 [no impairment] to 100 [maximum impairment]).

5. Percentage of Participants With Response (Response Rate). [Weeks 4, 8, 12, 20, 28, 36, 44 and 52]

   Clinical response was defined as > 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.

6. Percentage of Participants With Treatment Discontinuation (Treatment Discontinuation Rate). [Baseline to Week 52]

   The treatment discontinuation rate was calculated as the number of discontinued participants (ie, those withdrawn from the study without completing the Week 52 visit) divided by the number of all enrolled participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completed participation in Trial 31-12-293

• Written ICF obtained from a legally acceptable representative & informed assent at Baseline as applicable by trial center's IRB/IEC

• The subject, designated guardian(s) or caregiver(s) are able to comprehend and satisfactorily comply with the protocol requirements, as evaluated by the investigator

Exclusion Criteria:

• Experienced AEs during the double-blind trial (31-12-293) that would, in the investigator's judgment, preclude further exposure to aripiprazole.

• The subject had protocol violations during the double-blind trial considered major in the judgment of the investigator which would deem the subject a poor candidate for the trial

• A positive drug screen

• Sexually active patients not using 2 approved methods of contraception

• Females breastfeeding or pregnant (positive blood pregnancy test prior to receiving trial drug)

• Risk of committing suicide

• Body weight lower than 16 kg

• Abnormal laboratory test results, vital signs and ECG results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Dothan	Alabama	United States
2		Goodyear	Arizona	United States
3		Orange City	California	United States
4		Sacramento	California	United States
5		Wildomar	California	United States
6		Norwich	Connecticut	United States
7		Bradenton	Florida	United States
8		Orange City	Florida	United States
9		Tampa	Florida	United States
10		Atlanta	Georgia	United States
11		Indianapolis	Indiana	United States
12		Waldorf	Maryland	United States
13		Bloomfield Hills	Michigan	United States
14		Mt Arlington	New Jersey	United States
15		Summit	New Jersey	United States
16		Manhasset	New York	United States
17		Rochester	New York	United States
18		Avon Lake	Ohio	United States
19		Cleveland	Ohio	United States
20		Houston	Texas	United States
21		San Antonio	Texas	United States
22		Orem	Utah	United States
23		Salt Lake City	Utah	United States
24		Norfolk	Virginia	United States
25		Petersburg	Virginia	United States
26		Bellevue	Washington	United States
27		Toronto	Ontario	Canada
28		Whitby	Ontario	Canada
29		Nova Scotia		Canada
30		Budapest		Hungary
31		Szeged		Hungary
32		Catania		Italy
33		Milano		Italy

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

• Study Director: Eva Kohegyi, MD, Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01727713
• Other Study ID Numbers: 31-12-294
• First Posted: Nov 16, 2012
• Last Update Posted: Oct 16, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Tourette Syndrome; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Tic Disorders; Tics; Movement Disorders; Mental Disorders; Aripiprazole
• Additional relevant MeSH terms: Tic Disorders; Tics; Tourette Syndrome; Disease; Aripiprazole

Study Results

Participant Flow

Recruitment Details	The trial was conducted in 110 participants at 37 trials sites in 4 countries. Participants who were aged 7 to 17 years at screening or who turned 18 years during their participation in Trial 31-12-293 (NCT01727700) were enrolled in this extension trial

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Period Title: Overall Study
STARTED	110
COMPLETED	75
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Overall Participants	110
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	11.7 (2.9)
Sex: Female, Male (Count of Participants)
Female	24 21.8%
Male	86 78.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events.
Description	An AE is defined as any untoward medical occurrence in a patient or participant enrolled in the clinical trial and which does not necessarily have to have a causal relationship with the study drug. A treatment emergent adverse event (TEAE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to have a causal relationship with the study drug. Serious adverse event (SAE) or reaction is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolonged hospitalization, results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect.
Time Frame	Baseline, throighout the 52-week treatmetn and 30±3 days after last trial visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Participants with TEAEs	76.4 69.5%
Participants with severe TEAEs	4.5 4.1%
Participants with serious TEAEs	3.6 3.3%

2. Primary Outcome

Title	Percentage of Participants With Clinically Significant Abnormal Laboratory Test Results.
Description	Laboratory tests including hematology, serum chemistry, and urinalysis were performed for all the participants. The central laboratory was used for all laboratory testing whenever possible. Any value outside the normal range was flagged for the attention of the study physician who was to indicate whether the value was clinically significant based on the pre-defined criteria for identifying laboratory values of potential clinical relevance. Percentage of participants noted with abnormal laboratory values are reported below.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial and who had at least one post-baseline laboratory value were included.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Eosinophils (high) (N=108)	3.7 3.4%
Hemoglobin A1C (high) (N=107)	0.9 0.8%
Absolute neutrophils (low) (N=108)	13.0 11.8%
White blood count (low) (N=108)	4.6 4.2%
Total bilirubin (high) (N=108)	1.9 1.7%
Creatine phosphokinase (high) (N=108)	0.9 0.8%
Fasting glucose (high) (N=93)	3.2 2.9%
LDL cholesterol (high) (N=92)	3.3 3%
Triglycerides (high) (N=92)	17.4 15.8%
Uric acid (high) (N=108)	0.9 0.8%
Potassium (high) (N=108)	0.9 0.8%
Urine glucose (high) (N=104)	1.0 0.9%
Urine protein (high) (N=104)	1.9 1.7%
Prolactin (high) (N=104)	3.8 3.5%

3. Primary Outcome

Title	Percentage of Participants With Clinically Significant Abnormal Vital Signs.
Description	Vital sign measurements included systolic and diastolic blood pressure (BP) and heart rate, which were performed at all clinic visits. Criteria for identifying vital signs of potential clinical relevance included: Heart rate: ≥ 15 beats per minute (bpm) increase/decrease from Baseline (final visit of study 31-12-293); Systolic BP: ≥ 20 mmHg increase/decrease from Baseline; Diastolic BP: ≥ 15mmHg increase/decrease from Baseline; Orthostatic hypotension: ≥ 20 mmHg decrease in systolic BP and a ≥ 25 bpm increase in heart rate from supine to sitting/standing. Percentage of participants noted with abnormal vital sign measurements are reported below.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial and who who had at least one post-baseline vital sign result were included.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Heart rate-Supine (increase) (N=108)	0.9 0.8%
Heart rate-Supine (decrease) (N=108)	0.9 0.8%
Heart rate-Standing (increase) (N=108)	9.3 8.5%
Systolic Supine BP (decrease) (N=108)	6.5 5.9%
Systolic Standing BP (decrease) (N=108)	3.7 3.4%
Diastolic Supine BP (decrease) (N=108)	0.9 0.8%
Diastolic Standing BP (decrease) (N=108)	5.6 5.1%
Orthostatic hypotension (N=110)	2.7 2.5%

4. Primary Outcome

Title	Percentage of Participants With Clinically Significant Abnormal Electrocardiogram (ECG).
Description	Three 12-lead ECGs (scheduled 5 minutes apart) were recorded. Some of the pre-defined criteria for identifying ECG measurements of potential clinical relevance included: Tachycardia/sinus tachycardia: increase of ≥15 bpm from Baseline; increase in QTc of ≥10% from Baseline. The other abnormalities not present at Baseline and were present during the time of measurement were recorded. Percentage of participants noted with abnormal ECG findings are reported below.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial and who who had at least one post-baseline ECG result were included.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Tachycardia (N=106)	0.9 0.8%
Sinus Tachycardia (N=106)	0.9 0.8%
Supraventricular premature beat (N=106)	1.9 1.7%
Ventricular premature beat (N=106)	0.9 0.8%
Right bundle branch block (N=106)	1.9 1.7%
QTcB (N=106)	0.9 0.8%
QTcN (N=106)	0.9 0.8%

5. Primary Outcome

Title	Mean Change From Baseline in Body Weight.
Description	Criteria for identifying weight of potential clinical relevance was: ≥ 7% kilogram increase/decrease from Baseline (Final visit of Trial 31-12-293).
Time Frame	Baseline to Weeks 12, 28, 36, 44, 52/Last visit.

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial and who had at least one post-baseline weight measurement.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 12 (N=102)	1.8 (2.3)
Week 28 (N=90)	4.8 (3.8)
Week 36 (N=88)	5.8 (4.4)
Week 44 (N=81)	6.8 (5.3)
Week 52 (N=77)	8.0 (5.4)
Last visit (N=106)	7.2 (5.8)

6. Primary Outcome

Title	Mean Change From Baseline in Body Mass Index (BMI).
Description	BMI was calculated at the Baseline visit (using the Baseline height from study 31-12-293) and at Weeks 28 and 52/ET where height measured at baseline in the current trial was used to calculate BMI.
Time Frame	Baseline to Weeks 28, 52 and Last visit.

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug and who had a least one post-baseline BMI measurement.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 28 (N=90)	3.3 (16.2)
Week 52 (N=77)	1.9 (2.3)
Last visit (N=106)	1.8 (2.3)

7. Primary Outcome

Title	Mean Change From Baseline in Waist Circumference.
Description	Waist circumference was measured at Baseline, Weeks 12, 28, 36, 44, and the Week 52/last visit in centimeters.
Time Frame	Baseline to Weeks 12, 28, 36, 44, and 52/last visit.

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug and who had a least one post-baseline waist circumference measurement.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 12 (N=102)	2.2 (8.3)
Week 28 (N=90)	3.7 (9.7)
Week 36 (N=87)	3.5 (6.5)
Week 44 (N=80)	4.5 (6.7)
Week 52 (N=75)	5.5 (6.5)
Last visit (N=106)	4.6 (6.4)

8. Primary Outcome

Title	Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score.
Description	The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) were observed unobtrusively while the participant was at rest, and the investigator also made global judgments on the participant's dyskinesias (items 8 through 10). Each item was rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness/severe distress). In addition, the AIMS included 2 yes/no questions that addressed the subject's dental status (since an edentulous state can cause lingual dyskinesias). The AIMS movement rating score (range 0 to 28) was the sum of the rating scores for facial and oral moments (ie, items 1 to 4), extremity movements (ie, items 5 and 6), and trunk movements (ie, item 7).
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	-1.0 (3.0)
Week 8 (N=105)	-1.3 (3.4)
Week 12 (N=104)	-1.7 (3.7)
Week 20 (N=100)	-1.8 (3.9)
Week 28 (N=92)	-2.0 (4.3)
Week 36 (N=88)	-2.2 (4.5)
Week 44 (N=82)	-2.3 (4.6)
Week 52 (N=77)	-2.3 (4.7)
Last vist (N=109)	-1.8 (4.3)

9. Primary Outcome

Title	Change From Baseline in Simpson-Angus Scale (SAS) Total Score.
Description	The SAS 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). Each item was rated on a 5-point scale, with a score of 1 representing absence of symptoms, and a score of 5 representing a severe condition. The SAS total score (range 10 to 50) was the sum of the rating scores for 10 items from the SAS panel.
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	0.0 (0.9)
Week 8 (N=104)	-0.0 (0.9)
Week 12 (N=104)	-0.0 (0.9)
Week 20 (N=100)	-0.1 (0.7)
Week 28 (N=92)	-0.2 (0.8)
Week 36 (N=88)	-0.2 (0.8)
Week 44 (N=82)	-0.2 (0.8)
Week 52 (N=77)	-0.1 (0.8)
Last vist (N=109)	-0.1 (0.7)

10. Primary Outcome

Title	Change From Baseline in Barnes Akathisia Rating Scale (BARS) Total Score.
Description	The BARS Global Score is derived from the global clinical evaluation of akathisia on a 6-point scale, with 0 representing absence of symptoms and a score of 5 representing severe akathisia.
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	0.0 (0.4)
Week 8 (N=105)	0.0 (0.4)
Week 12 (N=104)	-0.0 (0.3)
Week 20 (N=100)	-0.1 (0.3)
Week 28 (N=92)	-0.1 (0.3)
Week 36 (N=88)	-0.1 (0.3)
Week 44 (N=82)	-0.1 (0.3)
Week 52 (N=77)	-0.1 (0.3)
Last vist (N=109)	-0.0 (0.3)

11. Primary Outcome

Title	Change From Baseline in Suicidal Ideation Intensity Total Score Based on Columbia-Suicide Severity Rating Scale (C-SSRS).
Description	The C-SSRS consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post baseline/"since last visit" evaluation that focuses on suicidality since the last trial visit. The C-SSRS data at Baseline and post baseline were summarized for incidence of reporting: Suicidality, Suicidal behavior (and its 4 types), Suicidal ideation (and its 5 types). The intensity score of each item ranges from 1 (least severe) to 5 (most severe), which leads to the range of the total score from 0 to 25.
Time Frame	Baseline, Weeks 1, 2, 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 1 (N=108)	-0.1 (0.7)
Week 2 (N=106)	-0.0 (0.5)
Week 4 (N=107)	0.0 (0.8)
Week 8 (N=105)	-0.1 (0.8)
Week 12 (N=104)	-0.0 (0.5)
Week 20 (N=100)	-0.1 (0.5)
Week 28 (N=92)	0.1 (1.0)
Week 36 (N=88)	0.1 (1.3)
Week 44 (N=82)	0.0 (0.0)
Week 52 (N=77)	0.2 (1.3)
Last vist (N=110)	0.0 (1.3)

12. Primary Outcome

Title	Change From Baseline in Average Score of Attention Deficit Disorder/Attention-deficit Hyperactivity Disorder (ADD/ADHD) of Swanson, Nolan, and Pelham-IV Rating Scale (SNAP-IV).
Description	The SNAP-IV Rating Scale is a revision of the SNAP Questionnaire. The SNAP-IV assesses inattention and hyperactivity/impulsivity, as well as oppositional defiant disorder that are often present in children with ADD/ADHD. The SNAP-IV was administered as a semi-structured interview with the participant and caregiver. The SNAP-IV is based on a 0 to 3 rating scale: not at all = 0, just a little = 1, quite a bit = 2, and very much = 3. The ADD/ADHD subscale includes items 1 through 19 (items 1-9 measure inattention, items 11-19 measure hyperactivity/ impulsivity, and item 10 for inattention domain), items 4, 8, 11, 31, and 32 measure inattention/overactivity, and items 21, 23, 29, 34, and 35 measure aggression/defiance. Items 4, 8, 11, 21, 32, 33, 36, 37, 38, and 39 form the Conners Index. Subscale average scores on the SNAP IV were calculated by summing the scores on the items in the subset and dividing by the number of items in the subset.
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	-0.2 (0.4)
Week 8 (N=105)	-0.2 (0.4)
Week 12 (N=104)	-0.3 (0.4)
Week 20 (N=100)	-0.2 (0.4)
Week 28 (N=92)	-0.2 (0.4)
Week 36 (N=88)	-0.2 (0.4)
Week 44 (N=82)	-0.2 (0.4)
Week 52 (N=77)	-0.2 (0.4)
Last vist (N=109)	-0.2 (0.5)

13. Primary Outcome

Title	Change From Baseline in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS).
Description	The CY-BOCS is a semi-structured interview used with children and adolescents aged 6 to 17 years to rate the severity and type of symptoms in participants with obsessive compulsive disorder. In general, the items depend on the participant's report; however, the final rating is based on the clinical judgment of the interviewer and should include additional information supplied by others. Nineteen items are rated in the CY-BOCS, but only items 1 through 10 (excluding items lb and 6b) are used to determine the total score. The total CY-BOCS score is the sum of items 1 through 10 (excluding lb and 6b), whereas the obsession and compulsion subtotals are the sums of items 1 through 5 (excluding lb) and 6 through 10 (excluding 6b), respectively. CY-BOCS total score could range from 0 to 40, and the obsession and compulsion subscale total scores could each range from 0 to 20. Higher scores indicate worse outcome.
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	-0.2 (2.6)
Week 8 (N=105)	-0.1 (3.0)
Week 12 (N=104)	-0.5 (2.7)
Week 20 (N=100)	-0.6 (3.0)
Week 28 (N=92)	-0.5 (3.3)
Week 36 (N=88)	-0.7 (3.4)
Week 44 (N=82)	-0.8 (3.7)
Week 52 (N=77)	-0.9 (3.9)
Last vist (N=109)	-0.7 (3.4)

14. Primary Outcome

Title	Change From Baseline in Children's Depression Rating Scale - Revised (CDRS-R).
Description	The CDRS-R is a brief rating scale based on a semi-structured interview with the child and an adult informant who knows the child well. Designed for 6- to 12-year-old children, and successfully used with adolescents, it can be administered in 15 to 20 minutes. The interviewer rates 17 symptom areas (including those that serve as Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for a diagnosis of depression): 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 and could range from 17 to 113 with higher values indicating worse outcome.
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	109
Week 4 (N=104)	-0.4 (4.4)
Week 8 (N=100)	-0.4 (3.8)
Week 12 (N=100)	-0.3 (3.2)
Week 20 (N=97)	-0.1 (4.2)
Week 28 (N=91)	0.2 (5.0)
Week 36 (N=87)	0.4 (4.4)
Week 44 (N=82)	-0.3 (3.3)
Week 52 (N=77)	0.6 (3.8)
Last vist (N=107)	0.7 (4.5)

15. Primary Outcome

Title	Change From Baseline in Pediatric Anxiety Rating Scale (PARS).
Description	The PARS is used to rate the severity of anxiety in children and adolescents, aged 6 to 17 years. 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. The 7-item severity list is used to determine severity of symptoms and the PARS total score. The time frame for the PARS 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 was the sum of items 2, 3, 5, 6, and 7. The total severity score ranged from 0 (no anxiety) to 25 (worst anxiety).
Time Frame	Baseline, Weeks 4, 8, 12, 20, 28, 36, 44, 52, and Last visit

Outcome Measure Data

Analysis Population Description

Safety Sample: All participants who received at least 1 dose of open-label study drug in this trial.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	-0.3 (3.0)
Week 8 (N=105)	-0.3 (3.6)
Week 12 (N=104)	-0.5 (2.6)
Week 20 (N=100)	-0.4 (2.9)
Week 28 (N=91)	-0.2 (3.1)
Week 36 (N=88)	-0.7 (3.0)
Week 44 (N=82)	-0.5 (2.7)
Week 52 (N=77)	-0.4 (3.5)
Last vist (N=109)	-0.4 (3.5)

16. Secondary Outcome

Title	Change From Baseline to Endpoint on the Total Tic Score (TTS) of the Yale Global Tic Severity Scale (YGTSS).
Description	The YGTSS is a semi-structured clinical interview which consists of a tic inventory, with 5 separate ratings to assess the number, intensity, frequency, complexity and interference of tics, plus an overall impairment/disability score. Ratings are made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics each, including number, frequency, intensity, complexity, and interference. Summation of these 10 scores (ie, 0-50) provides a TTS that was the secondary outcome measure in this trial. The YGTSS ranking of impairment, with a maximum of 50 points, is based on the impact of the tic disorder on areas of self-esteem, family life, social acceptance, and school scores. The total severity score ranged from 0 (no impairment) to 50 (worst impairment).
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who receive at least 1 dose of open-label study drug in this trial, and have baseline and at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 52 (N=77)	-8.6 (10.2)
Last visit (N=109)	-6.6 (10.9)

17. Secondary Outcome

Title	Mean Clinical Global Impressions for Tourette's Syndrome (CGI-TS) Change Score at Endpoint.
Description	The CGI is a 7-point Likert scale used in a multitude of clinical trials as a clinical global measure to assess the severity and change in disease symptomatology (ie, tics). The CGI was included as a secondary scale to provide a more complete assessment of clinical efficacy. To assess CGI-TS severity, the rater or investigator will answer the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" However, the evaluation of illness will be limited to manifestations of Tourette's Disorder only. Response choices include: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who receive at least 1 dose of open-label study drug in this trial, and have baseline and at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 52 (N=77)	2.5 (1.6)
Last visit (N=109)	2.5 (1.6)

18. Secondary Outcome

Title	Change From Baseline to Endpoint in CGI-TS Severity of Illness Score.
Description	The final CGI-TS score was compared to the participant's baseline condition at the time of entry into the open-label study, rather than the CGI-TS baseline condition at the time participants enrolled into the preceding study. 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.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who receive at least 1 dose of open-label study drug in this trial, and have baseline and at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 52 (N=77)	-0.9 (1.2)
Last visit (N=109)	-0.7 (1.3)

19. Secondary Outcome

Title	Mean Change From Baseline to Endpoint 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) for motor and vocal tics, and an impairment ranking. The YGTSS TTS is the summation of the severity scores of motor and vocal tics (range of 0 [no impairment] to 50 [maximum impairment]). The total YGTSS score is the summation of the severity scores of motor and vocal tics and the ranking of impairment (total range of 0 [no impairment] to 100 [maximum impairment]).
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who receive at least 1 dose of open-label study drug in this trial, and have baseline and at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 52 (N=77)	-18.0 (23.7)
Last visit (N=109)	-14.0 (24.3)

20. Secondary Outcome

Title	Percentage of Participants With Response (Response Rate).
Description	Clinical response was defined as > 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.
Time Frame	Weeks 4, 8, 12, 20, 28, 36, 44 and 52

Outcome Measure Data

Analysis Population Description

All participants who receive at least 1 dose of open-label study drug in this trial, and have baseline and at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Week 4 (N=107)	80.4 73.1%
Week 8 (N=105)	81.9 74.5%
Week 12 (N=104)	82.7 75.2%
Week 20 (N=100)	75.0 68.2%
Week 28 (N=92)	77.2 70.2%
Week 36 (N=88)	75.0 68.2%
Week 44 (N=81)	75.3 68.5%
Week 52 (N=77)	67.5 61.4%

21. Secondary Outcome

Title	Percentage of Participants With Treatment Discontinuation (Treatment Discontinuation Rate).
Description	The treatment discontinuation rate was calculated as the number of discontinued participants (ie, those withdrawn from the study without completing the Week 52 visit) divided by the number of all enrolled participants.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants who receive at least 1 dose of open-label study drug in this trial, and have baseline and at least 1 post-baseline efficacy evaluation.

Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
Measure Participants	110
Number [Percentage of discontinued participants]	31.8 28.9%

Adverse Events

Time Frame	Day 0 (Baseline) until Follow-up 30 Days (±3 days) after the last trial visit.
Arm/Group Title	Open-label Aripiprazole
Arm/Group Description	All participants in this open-label extension trial were assigned to once-daily aripiprazole, which was flexibly dosed at the discretion of the investigator on the basis of treatment response and medication tolerability.
All Cause Mortality
	Open-label Aripiprazole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open-label Aripiprazole
	Affected / at Risk (%)	# Events
Total	4/110 (3.6%)
Congenital, familial and genetic disorders
Tourette's disorder	1/110 (0.9%)	1
Infections and infestations
Appendicitis	1/110 (0.9%)	1
Infectious mononucleosis	1/110 (0.9%)	1
Injury, poisoning and procedural complications
Concussion	1/110 (0.9%)	1
Intentional overdose	1/110 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Open-label Aripiprazole
	Affected / at Risk (%)	# Events
Total	84/110 (76.4%)
Blood and lymphatic system disorders
Leukopenia	1/110 (0.9%)	1
Neutropenia	2/110 (1.8%)	2
Cardiac disorders
Tachycardia	1/110 (0.9%)	1
Ear and labyrinth disorders
Ear pain	1/110 (0.9%)	1
Middle ear effusion	1/110 (0.9%)	1
Tympanic membrane perforation	1/110 (0.9%)	1
Eye disorders
Excessive eye blinking	1/110 (0.9%)	1
Eye inflammation	1/110 (0.9%)	1
Strabismus	1/110 (0.9%)	1
Vision blurred	2/110 (1.8%)	2
Gastrointestinal disorders
Abdominal discomfort	1/110 (0.9%)	1
Abdominal pain	1/110 (0.9%)	2
Abdominal pain upper	2/110 (1.8%)	2
Aphthous stomatitis	1/110 (0.9%)	2
Constipation	3/110 (2.7%)	4
Diarrhoea	3/110 (2.7%)	3
Dry mouth	1/110 (0.9%)	1
Eructation	1/110 (0.9%)	2
Flatulence	1/110 (0.9%)	1
Nausea	8/110 (7.3%)	9
Retching	1/110 (0.9%)	1
Salivary hypersecretion	2/110 (1.8%)	3
Vomiting	10/110 (9.1%)	12
General disorders
Fatigue	11/110 (10%)	12
Influenza like illness	1/110 (0.9%)	1
Irritability	2/110 (1.8%)	3
Malaise	1/110 (0.9%)	1
Pyrexia	7/110 (6.4%)	8
Hepatobiliary disorders
Hepatitis acute	1/110 (0.9%)	1
Immune system disorders
House dust allergy	1/110 (0.9%)	1
Multiple allergies	1/110 (0.9%)	1
Seasonal allergy	3/110 (2.7%)	3
Infections and infestations
Ear infection	2/110 (1.8%)	2
Gastroenteritis	5/110 (4.5%)	5
Gastroenteritis viral	4/110 (3.6%)	5
Gastrointestinal viral infection	1/110 (0.9%)	1
Influenza	4/110 (3.6%)	4
Localised infection	1/110 (0.9%)	1
Nasopharyngitis	11/110 (10%)	12
Otitis media	1/110 (0.9%)	1
Pharyngitis	1/110 (0.9%)	1
Pharyngitis streptococcal	2/110 (1.8%)	2
Pneumonia	1/110 (0.9%)	2
Sinusitis	5/110 (4.5%)	5
Tonsillitis	1/110 (0.9%)	1
Upper respiratory tract infection	4/110 (3.6%)	4
Viral infection	2/110 (1.8%)	2
Viral rash	1/110 (0.9%)	1
Injury, poisoning and procedural complications
Animal bite	1/110 (0.9%)	1
Contusion	1/110 (0.9%)	1
Excoriation	1/110 (0.9%)	1
Hand fracture	1/110 (0.9%)	1
Ligament sprain	2/110 (1.8%)	2
Patella fracture	1/110 (0.9%)	1
Investigations
Bilirubin conjugated increased	1/110 (0.9%)	1
Blood creatine phosphokinase increased	1/110 (0.9%)	1
Blood pressure increased	1/110 (0.9%)	1
Blood thyroid stimulating hormone increased	1/110 (0.9%)	1
Protein urine present	1/110 (0.9%)	1
Weight increased	26/110 (23.6%)	27
White blood cell count decreased	1/110 (0.9%)	1
Metabolism and nutrition disorders
Hyperinsulinaemia	2/110 (1.8%)	2
Increased appetite	6/110 (5.5%)	6
Insulin resistance	1/110 (0.9%)	1
Iron deficiency	1/110 (0.9%)	1
Vitamin D deficiency	1/110 (0.9%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/110 (0.9%)	1
Muscle spasms	1/110 (0.9%)	1
Pain in extremity	3/110 (2.7%)	3
Nervous system disorders
Akathisia	3/110 (2.7%)	3
Cognitive disorder	1/110 (0.9%)	1
Dizziness	5/110 (4.5%)	6
Dyskinesia	1/110 (0.9%)	1
Dystonia	2/110 (1.8%)	2
Headache	11/110 (10%)	12
Migraine	1/110 (0.9%)	1
Migraine with aura	1/110 (0.9%)	1
Paresthesia	1/110 (0.9%)	1
Psychomotor hyperactivity	1/110 (0.9%)	1
Sedation	6/110 (5.5%)	6
Somnolence	13/110 (11.8%)	14
Syncope	1/110 (0.9%)	1
Tremor	2/110 (1.8%)	2
Psychiatric disorders
Aggression	3/110 (2.7%)	4
Agitation	4/110 (3.6%)	6
Anger	2/110 (1.8%)	2
Anxiety	6/110 (5.5%)	6
Attention deficit/hyperactivity disorder	5/110 (4.5%)	6
Blunted affect	1/110 (0.9%)	1
Bruxism	1/110 (0.9%)	1
Depression	2/110 (1.8%)	3
Depressed mood	2/110 (1.8%)	2
Emotional disorder	1/110 (0.9%)	1
Emotional poverty	1/110 (0.9%)	1
Flat affect	1/110 (0.9%)	1
Head banging	1/110 (0.9%)	1
Initial insomnia	1/110 (0.9%)	1
Insomnia	3/110 (2.7%)	3
Mood altered	1/110 (0.9%)	1
Obsessive-compulsive disorder	1/110 (0.9%)	1
Restlessness	1/110 (0.9%)	1
Sleep disorder	1/110 (0.9%)	1
Somnambulism	1/110 (0.9%)	1
Suicidal ideation	3/110 (2.7%)	3
TIC	6/110 (5.5%)	9
Renal and urinary disorders
Pollakiuria	1/110 (0.9%)	1
Urinary hesitation	1/110 (0.9%)	1
Urinary incontinence	1/110 (0.9%)	1
Urinary retention	1/110 (0.9%)	1
Reproductive system and breast disorders
Dysmenorrhoea	2/110 (1.8%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/110 (1.8%)	3
Epistaxis	2/110 (1.8%)	4
Hiccups	1/110 (0.9%)	1
Nasal congestion	1/110 (0.9%)	2
Oropharyngeal pain	3/110 (2.7%)	3
Rhinitis allergic	1/110 (0.9%)	1
Rhinorrhoea	3/110 (2.7%)	4
Sleep apnoea syndrome	1/110 (0.9%)	1
Vocal cord disorder	1/110 (0.9%)	1
Skin and subcutaneous tissue disorders
Acne	1/110 (0.9%)	1
Rash	1/110 (0.9%)	1
Vascular disorders
Hot flush	1/110 (0.9%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.