Trial Outcomes & Findings for Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder (NCT NCT01418339)
NCT ID: NCT01418339
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 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.
COMPLETED
PHASE3
135 participants
Baseline to Week 8
2021-10-07
Participant Flow
A total of 152 participants were screened and 135 were randomized to the treatment. The randomized participants were recruited from 45 study sites in the following 6 countries: United States (US), Hungary, Canada, Taiwan, South Korea, and Mexico. Out of 135, 124 participants were included in the modified intention-to-treat (mITT) population.
The study consisted of a Pretreatment and Treatment Phase. The Pretreatment Phase consisted of a Screening Period, Washout Period (when applicable), and Baseline visit. This was followed by an 8-week Treatment Phase. There was also a Follow-up Period (30 days) for participants who did not roll over into the open-label study 31-10-274 (NCT01416441).
Participant milestones
| Measure |
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.
|
Placebo
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
Overall Study
STARTED
|
90
|
45
|
|
Overall Study
COMPLETED
|
78
|
35
|
|
Overall Study
NOT COMPLETED
|
12
|
10
|
Reasons for withdrawal
| Measure |
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.
|
Placebo
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
Overall Study
Adverse Event
|
5
|
2
|
|
Overall Study
Subject Withdrew Consent
|
1
|
2
|
|
Overall Study
Lack of Efficacy as Determined by the Investigator
|
6
|
6
|
Baseline Characteristics
Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder
Baseline characteristics by cohort
| Measure |
Aripiprazole
n=90 Participants
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.
|
Placebo
n=45 Participants
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner
|
Total
n=135 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
11.9 Years
STANDARD_DEVIATION 2.8 • n=99 Participants
|
11.7 Years
STANDARD_DEVIATION 2.6 • n=107 Participants
|
11.9 Years
STANDARD_DEVIATION 2.7 • n=206 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
73 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
104 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
20 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
33 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
67 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
98 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
28 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
40 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
53 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
84 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Yale Global Tic Severity Scale (YGTSS) -Total Tic Score (TTS)
|
30.5 score on a scale
STANDARD_DEVIATION 6.6 • n=99 Participants
|
29.3 score on a scale
STANDARD_DEVIATION 7.0 • n=107 Participants
|
30.1 score on a scale
STANDARD_DEVIATION 6.7 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 8Population: 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.
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.
Outcome measures
| Measure |
Aripiprazole
n=71 Participants
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.
|
Placebo
n=34 Participants
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS)
|
-12.34 score on a scale
Standard Error 0.88
|
-7.72 score on a scale
Standard Error 1.23
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: 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.
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.
Outcome measures
| Measure |
Aripiprazole
n=70 Participants
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.
|
Placebo
n=33 Participants
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score
|
2.29 score on a scale
Standard Error 0.12
|
2.81 score on a scale
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Baseline to Week 8Population: 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.
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.
Outcome measures
| Measure |
Aripiprazole
n=71 Participants
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.
|
Placebo
n=34 Participants
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
Change From Baseline in Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) Total Score
|
10.04 score on a scale
Standard Error 1.83
|
12.04 score on a scale
Standard Error 2.60
|
Adverse Events
Aripiprazole
Placebo
Serious adverse events
| Measure |
Aripiprazole
n=90 participants at risk
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.
|
Placebo
n=45 participants at risk
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
General disorders
Hyperthermia
|
1.1%
1/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Investigations
Alanine aminotransferase increased
|
1.1%
1/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Investigations
Aspartate aminotransferase increased
|
1.1%
1/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
1.1%
1/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Investigations
Electrocardiogram QT prolonged
|
1.1%
1/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Nervous system disorders
Dystonia
|
2.2%
2/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
Other adverse events
| Measure |
Aripiprazole
n=90 participants at risk
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.
|
Placebo
n=45 participants at risk
Participants randomized to placebo received aripiprazole-matching placebo tablet, orally, QW for 8 weeks in a double-blind manner.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
13.3%
12/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
8.9%
4/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
9/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
2.2%
1/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
General disorders
Fatigue
|
8.9%
8/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
0.00%
0/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Increased Appetite
|
6.7%
6/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
2.2%
1/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
13.3%
12/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
4.4%
2/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
|
Nervous system disorders
Somnolence
|
16.7%
15/90 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
6.7%
3/45 • From first dose up to 30 days post last dose (Up to approximately 12 weeks)
Safety Sample included all participants in the ITT Sample who received at least 1 dose of study drug.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
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