Efficacy & Safety Study of Once-weekly Oral Aripiprazole... | NCT01418339

ID	Type	Description	Link
2011-000467-27	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Aripiprazole	Experimental	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.	Drug: Aripiprazole
Placebo	Placebo Comparator	Participants randomized to placebo received aripiprazole-matching placebo, tablet, orally, QW for 8 weeks in a double-blind manner.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Aripiprazole	Drug	Aripiprazole tablet administered orally once a week.	Aripiprazole

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS)	The YGTSS is a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The TTS ranged from 0 (none) to 50 (severe) with a higher score represent more severe symptoms (greater reduction from baseline for greater improvement). Mixed Effect Repeated Measure Model (MMRM) analysis was performed.	Baseline to Week 8

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score	The severity of illness and efficacy of study medication for each participant were rated using the CGI-TS scale. The study physician rated the participants total improvement whether or not it is due to study treatment. All responses were compared to the participants condition at Baseline (Day 0). Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients), with lower score indicating better improvement. A negative change from Baseline indicates improvement. MMRM analysis was performed.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

7 to 17 year old with diagnostic and statistical manual of mental disorders, fourth edition -text revision (DSM-IV-TR) diagnostic criteria for Tourette's disorder (TD), confirmed by the kiddie schedule for affective disorders and schizophrenia - present and lifetime version (K-SADS-PL), including the Diagnostic Supplement 5
Has a total tic score (TTS) ≥20 on the yale global tic severity scale (YGTSS) at Screening and Baseline
Presenting tic symptoms cause impairment in the participant's normal routines, which include academic achievement, occupational functioning, social activities, and/or relationships
Females of childbearing potential must have a negative pregnancy test, must be practicing acceptable double-barrier methods of contraception, and must not be pregnant or lactating.
Written informed consent form (ICF) obtained from a legally acceptable representative & informed assent at Screening as applicable by study center's Institutional review board/independent ethics committee (IRB/IEC)
The participant, designated guardian(s) or caregiver(s) are able to comprehend and satisfactorily comply with the protocol requirements, as evaluated by the investigator.

Exclusion Criteria:

Clinical presentation and/or history, consistent with another neurologic condition that may have accompanying abnormal movements.
History of schizophrenia, bipolar disorder, or other psychotic disorder.
Participant receiving psychostimulants for treatment of attention-deficit disorder/Attention-deficit hyperactivity disorder (ADD/ADHD) and who have developed and/or had exacerbations of tic disorder after initiation of stimulant treatment.
Currently meets DSM-IV-TR criteria for a primary mood disorder.
Severe obsessive-compulsive disorder (OCD), per children's yale-brown obsessive compulsive scale (CY-BOCS) score >16.
Taken aripiprazole within 30 days of the Screening visit.
Received any investigational agent in a clinical trial within 30 days prior to Screening or who were randomized into a clinical trial with Once-weekly aripiprazole at any time.
History of neuroleptic malignant syndrome.
Sexually active participants not using 2 approved methods of contraception; breastfeeding or pregnant.
Risk of committing suicide
Bodyweight lower than 16 kg
Taken neuroleptic or antiparkinson drugs <14 days prior to randomization.
Requiring cognitive-behavioral therapy (CBT) for TD during study.
Participant meets DSM-IV-TR criteria for any significant psychoactive substance use disorder within the past 3 months.
Positive drug screen
Participant requires medications not allowed per protocol
Use of CYP2D6 and CYP3A4 inhibitors or CYP3A4 inducers within 14 days prior to dosing and for duration of study.
Inability to swallow tablets or tolerate oral medication
Abnormal laboratory test results, vital signs and Electrocardiogram (ECG) results

Name	Affiliation	Role
Eva Kohegyi, MD	Otsuka Pharmaceutical Development & Commercialization, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Little Rock	Arkansas	72205	United States

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Aripiprazole	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Aripiprazole	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.
BG001	Placebo	Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00011.9± 2.8 BG00111.7± 2.6 BG00211.9± 2.7

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00017 BG00114 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00020 BG00113 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0002 BG0010 BG002

Yale Global Tic Severity Scale (YGTSS) -Total Tic Score (TTS)

The YGTSS is a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The total tic score (TTS) ranged from 0 (none) to 50 (severe) with higher score represent more severe symptoms.

Mean

Standard Deviation

score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00030.5± 6.6 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS)

The YGTSS is a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0 to 5 for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The TTS ranged from 0 (none) to 50 (severe) with a higher score represent more severe symptoms (greater reduction from baseline for greater improvement). Mixed Effect Repeated Measure Model (MMRM) analysis was performed.

Modified Intention-to-Treat (mITT) included all participants randomly assigned to the double-blind treatment, excluding participants from the two sites that were terminated. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Week 8

ID	Title	Description
OG000	Aripiprazole	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.
OG001	Placebo	Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.

Units	Counts
Participants	OG00071 OG00134

Title

Denominators

Categories

Title	Measurements
	OG000-12.34± 0.88 OG001-7.72± 1.23

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The statistical comparison was performed using MMRM model at a significance level of 0.05 (2-sided).	MMRM		=0.0028	P-value was derived from a repeated measures linear model with treatment, week, and treatment by week interaction as fixed categorical effects, the baseline value as a fixed covariate, and week as the time variable for repeated measures.	Treatment Difference	-4.63			2-Sided	95	-7.62	-1.63					Superiority

Secondary

Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score

The severity of illness and efficacy of study medication for each participant were rated using the CGI-TS scale. The study physician rated the participants total improvement whether or not it is due to study treatment. All responses were compared to the participants condition at Baseline (Day 0). Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill patients), with lower score indicating better improvement. A negative change from Baseline indicates improvement. MMRM analysis was performed.

mITT included all participants randomly assigned to the double-blind treatment, excluding participants from the two sites that were terminated. Overall number of participants analyzed is the number of participants with data available for analyses.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Week 8

ID	Title	Description
OG000	Aripiprazole	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.

Secondary

Change From Baseline in Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) Total Score

The GTS-QOL is a disease-specific patient-reported scale for the measurement of health-related quality of life in participants with Tourette's Disorder, taking into account the complexity of the clinical picture of the disease. The questionnaire consists of a 27-item Tourette's Disorder-specific scale with 4 subscales (psychological, physical, obsessional, and cognitive). The GTS-QOL total score ranged from 0 (extremely dissatisfied with life) and 100 (extremely satisfied with life). A positive change from Baseline indicates improvement. MMRM analysis was performed.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Week 8

ID	Title	Description
OG000	Aripiprazole	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Aripiprazole	Aripiprazole was administered orally once a week (QW) for 8 weeks in a double-blind manner. Participants randomized to aripiprazole received aripiprazole tablets at a starting dose of 52.5 milligrams (mg) QW on Day 0. At Week 1, according to the investigator's discretion based on efficacy and tolerability, the dose of aripiprazole could remain at 52.5 mg QW or could be increased to 77.5 mg QW. The dose could be increased to 110 mg QW as early as Week 2. For the remainder of the study (up to Week 8), the dose was to be adjusted up and down among these three dose levels, as determined by the investigator.	0	90	3	90	38	90
EG001	Placebo	Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.	0	45	0	45	8	45

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hyperthermia	General disorders	MedDra 16.0	Systematic Assessment	EG0001 affected90 at risk EG0010 affected45 at risk
Alanine aminotransferase increased	Investigations	MedDra 16.0	Systematic Assessment	EG0001 affected90 at risk EG0010 affected45 at risk
Aspartate aminotransferase increased	Investigations	MedDra 16.0	Systematic Assessment	EG0001 affected90 at risk EG0010 affected45 at risk
Blood creatine phosphokinase increased	Investigations	MedDra 16.0	Systematic Assessment	EG0001 affected90 at risk EG0010 affected45 at risk
Electrocardiogram QT prolonged	Investigations	MedDra 16.0	Systematic Assessment	EG0001 affected90 at risk EG0010 affected45 at risk
Dystonia	Nervous system disorders	MedDra 16.0	Systematic Assessment	EG0002 affected90 at risk EG0010 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDra 16.0	Systematic Assessment	EG00012 affected90 at risk EG0014 affected45 at risk
Vomiting	Gastrointestinal disorders	MedDra 16.0	Systematic Assessment	EG0009 affected90 at risk EG0011 affected45 at risk
Fatigue	General disorders	MedDra 16.0	Systematic Assessment	EG0008 affected90 at risk EG0010 affected45 at risk
Increased Appetite	Metabolism and nutrition disorders	MedDra 16.0	Systematic Assessment	EG0006 affected90 at risk EG0011 affected45 at risk
Headache	Nervous system disorders	MedDra 16.0	Systematic Assessment	EG00012 affected90 at risk EG0012 affected45 at risk
Somnolence	Nervous system disorders	MedDra 16.0	Systematic Assessment	EG00015 affected90 at risk EG0013 affected45 at risk

ID	Term
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D065886	Neurodevelopmental Disorders
D001523	Mental Disorders

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring