Trial Outcomes & Findings for Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder (TD) (NCT NCT01418352)

Last Updated: 2021-10-07

Results Overview

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 (greater reduction from baseline for greater improvement).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

83 participants

Primary outcome timeframe

Baseline and Week 8

Results posted on

2021-10-07

Participant Flow

A total of 105 participants were screened and 83 were randomized to the treatment. The randomized participants were recruited at 38 sites in the following 5 countries: Bulgaria, Germany, Romania, Ukraine, and the US.

This study consisted of 2 distinct phases: a Pre-treatment Phase and a Treatment Phase. The Pre-treatment Phase consisted of a Screening period, a Washout period, and a Baseline visit. This was followed by an 8-week Treatment Phase. There was a follow-up period (30 days) for those participants who did not roll-over into the Open-label Study 31-10-274 (NCT01416441).

Participant milestones

Participant milestones
Measure	Aripiprazole 52.5 mg Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg Participants received aripiprazole 77.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg Participants received aripiprazole 110 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo Participants received aripiprazole matching placebo, tablets, orally, once weekly for the 8-week Double-blind Treatment Period.
Overall Study STARTED	20	21	21	21
Overall Study COMPLETED	17	17	16	18
Overall Study NOT COMPLETED	3	4	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Aripiprazole 52.5 mg Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg Participants received aripiprazole 77.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg Participants received aripiprazole 110 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo Participants received aripiprazole matching placebo, tablets, orally, once weekly for the 8-week Double-blind Treatment Period.
Overall Study Lost to Follow-up	2	0	0	0
Overall Study Adverse Event	0	1	0	0
Overall Study Sponsor Discontinued Trial Site	0	2	2	2
Overall Study Subject Withdrew Consent	0	1	2	1
Overall Study Protocol Deviation	0	0	1	0
Overall Study Lack of Efficacy as Determined by the Investigator	1	0	0	0

Baseline Characteristics

Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder (TD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aripiprazole 52.5 mg n=20 Participants Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg n=21 Participants Participants received aripiprazole 77.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg n=21 Participants Participants received aripiprazole 110 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo n=21 Participants Participants received aripiprazole matching placebo tablets, orally, once weekly for the 8-week Double-blind Treatment Period.	Total n=83 Participants Total of all reporting groups
Age, Continuous	11.5 Years STANDARD_DEVIATION 3.4 • n=39 Participants	11.7 Years STANDARD_DEVIATION 2.8 • n=41 Participants	12.5 Years STANDARD_DEVIATION 2.7 • n=35 Participants	11.8 Years STANDARD_DEVIATION 2.7 • n=31 Participants	11.9 Years STANDARD_DEVIATION 2.9 • n=146 Participants
Age, Customized 7 to 12 years	12 Participants n=39 Participants	11 Participants n=41 Participants	11 Participants n=35 Participants	14 Participants n=31 Participants	48 Participants n=146 Participants
Age, Customized 13 to 17 years	8 Participants n=39 Participants	10 Participants n=41 Participants	10 Participants n=35 Participants	7 Participants n=31 Participants	35 Participants n=146 Participants
Sex: Female, Male Female	3 Participants n=39 Participants	8 Participants n=41 Participants	3 Participants n=35 Participants	6 Participants n=31 Participants	20 Participants n=146 Participants
Sex: Female, Male Male	17 Participants n=39 Participants	13 Participants n=41 Participants	18 Participants n=35 Participants	15 Participants n=31 Participants	63 Participants n=146 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants	2 Participants n=41 Participants	1 Participants n=35 Participants	2 Participants n=31 Participants	5 Participants n=146 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=39 Participants	19 Participants n=41 Participants	20 Participants n=35 Participants	19 Participants n=31 Participants	78 Participants n=146 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants	0 Participants n=146 Participants
Race/Ethnicity, Customized White	12 Participants n=39 Participants	19 Participants n=41 Participants	19 Participants n=35 Participants	19 Participants n=31 Participants	69 Participants n=146 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=39 Participants	2 Participants n=41 Participants	2 Participants n=35 Participants	2 Participants n=31 Participants	14 Participants n=146 Participants
Weight	44.7 Kilogram STANDARD_DEVIATION 16.3 • n=39 Participants	49.0 Kilogram STANDARD_DEVIATION 16.2 • n=41 Participants	52.8 Kilogram STANDARD_DEVIATION 19.6 • n=35 Participants	45.0 Kilogram STANDARD_DEVIATION 12.5 • n=31 Participants	47.9 Kilogram STANDARD_DEVIATION 16.4 • n=146 Participants
Height	148.5 centimeter STANDARD_DEVIATION 19.0 • n=39 Participants	151.8 centimeter STANDARD_DEVIATION 16.5 • n=41 Participants	157.5 centimeter STANDARD_DEVIATION 14.8 • n=35 Participants	151.8 centimeter STANDARD_DEVIATION 14.4 • n=31 Participants	152.4 centimeter STANDARD_DEVIATION 16.3 • n=146 Participants
BMI (Body Mass Index)	19.6 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 3.7 • n=39 Participants	20.7 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 3.8 • n=41 Participants	20.6 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 4.9 • n=35 Participants	19.3 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 3.7 • n=31 Participants	20.0 kilogram per meter squared (kg/m^2) STANDARD_DEVIATION 4.0 • n=146 Participants
Time since first diagnosis for Tourette's Disorder	3.5 years STANDARD_DEVIATION 3.0 • n=39 Participants	1.8 years STANDARD_DEVIATION 2.5 • n=41 Participants	3.0 years STANDARD_DEVIATION 3.5 • n=35 Participants	2.6 years STANDARD_DEVIATION 2.3 • n=31 Participants	2.7 years STANDARD_DEVIATION 2.9 • n=146 Participants
Yale Global Tic Severity Scale Total Tic Score (YGTSS TTS)	28.2 score on a scale STANDARD_DEVIATION 5.6 • n=39 Participants	30.1 score on a scale STANDARD_DEVIATION 5.8 • n=41 Participants	31.4 score on a scale STANDARD_DEVIATION 6.7 • n=35 Participants	31.1 score on a scale STANDARD_DEVIATION 5.5 • n=31 Participants	30.2 score on a scale STANDARD_DEVIATION 6 • n=146 Participants

PRIMARY outcome

Timeframe: Baseline and Week 8

Population: The Intention-to-Treat (ITT) Sample included participants randomly assigned to the double-blind treatment (regardless of whether or not they were dosed with study drug). Overall number of participants analyzed are participants with data available for analyses.

Outcome measures

Outcome measures
Measure	Aripiprazole 52.5 mg n=17 Participants Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg n=17 Participants Participants received aripiprazole 77.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg n=16 Participants Participants received aripiprazole 110 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo n=18 Participants Participants received aripiprazole matching placebo, tablets, orally, once weekly for the 8-week Double-blind Treatment Period.
Mean Change From Baseline to Week 8 in Yale Global Tic Severity Scale (YGTSS) Total Tic Score	-8.2 score on scale Standard Deviation 4.8	-9.9 score on scale Standard Deviation 6.7	-14.5 score on scale Standard Deviation 7.7	-9.6 score on scale Standard Deviation 7.5

SECONDARY outcome

Timeframe: Baseline and Week 8

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

Outcome measures
Measure	Aripiprazole 52.5 mg n=17 Participants Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg n=17 Participants Participants received aripiprazole 77.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg n=16 Participants Participants received aripiprazole 110 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo n=18 Participants Participants received aripiprazole matching placebo, tablets, orally, once weekly for the 8-week Double-blind Treatment Period.
Mean Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score	-0.9 score on scale Standard Deviation 0.6	-1.1 score on scale Standard Deviation 0.9	-1.3 score on scale Standard Deviation 1.0	-1.0 score on scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline and Week 8

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

Outcome measures
Measure	Aripiprazole 52.5 mg n=17 Participants Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg n=17 Participants Participants received aripiprazole 77.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg n=16 Participants Participants received aripiprazole 110 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo n=18 Participants Participants received aripiprazole matching placebo, tablets, orally, once weekly for the 8-week Double-blind Treatment Period.
Mean Change From Baseline in Gilles de la Tourette Quality of Life (GTS-QOL) Overall Score at Week 8	8.8 score on scale Standard Deviation 14.1	3.8 score on scale Standard Deviation 24.4	13.1 score on scale Standard Deviation 20.9	13.4 score on scale Standard Deviation 15.9

Adverse Events

Aripiprazole 52.5 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Aripiprazole 77.5 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Aripiprazole 110 mg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Matching Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: [email protected]

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

Measure	Aripiprazole 52.5 mg n=20 participants at risk Participants received aripiprazole 52.5 mg, tablet, orally, once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 77.5 mg n=21 participants at risk Participants received aripiprazole 77.5 mg, tablet, orally once weekly for the 8-week Double-blind Treatment Period.	Aripiprazole 110 mg n=21 participants at risk Participants received aripiprazole 110 mg, tablet, orally once weekly for the 8-week Double-blind Treatment Period.	Matching Placebo n=21 participants at risk Participants received aripiprazole matching placebo, tablets, orally, once weekly for the 8-week Double-blind Treatment Period.
Cardiac disorders Tachycardia	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Gastrointestinal disorders Abdominal Pain	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Gastrointestinal disorders Diarrhoea	0.00% 0/20 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Gastrointestinal disorders Nausea	10.0% 2/20 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	14.3% 3/21 • Number of events 3 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Gastrointestinal disorders Vomiting	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
General disorders Fatigue	0.00% 0/20 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	19.0% 4/21 • Number of events 4 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Infections and infestations Nasopharyngitis	0.00% 0/20 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Investigations Drug Prolactin Decreased	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Investigations Weight Increased	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/20 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Nervous system disorders Dizziness	10.0% 2/20 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Nervous system disorders Headache	10.0% 2/20 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	38.1% 8/21 • Number of events 8 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	9.5% 2/21 • Number of events 2 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Nervous system disorders Sedation	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	4.8% 1/21 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Nervous system disorders Somnolence	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	14.3% 3/21 • Number of events 3 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	28.6% 6/21 • Number of events 6 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Nervous system disorders Tremor	5.0% 1/20 • Number of events 1 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)	0.00% 0/21 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)