Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 60 of 405 for:    ARIPIPRAZOLE

Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01727700
Recruitment Status : Completed
First Posted : November 16, 2012
Results First Posted : February 13, 2015
Last Update Posted : February 13, 2015
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Tourette's Disorder
Tic Disorder
Interventions Drug: Aripiprazole
Drug: Placebo
Enrollment 133
Recruitment Details This was a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial in children and adolescents (aged 7-17 years) with Tourette's disorder (TD). 171 participants were screened, of which 133 were randomized to treatment.
Pre-assignment Details The trial consisted of a pretreatment phase and a treatment phase. Pretreatment phase consisted of a screening and washout (when applicable) period. This was followed by an 8-week treatment phase starting with the baseline visit (Day 0). Particpants were randomized 1:1:1 to aripiprazole high dose, aripiprazole low dose or placebo.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose. For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose. Participants received matching placebo tablets in the same way as aripiprazole.
Period Title: Overall Study
Started 44 45 44
Completed 42 35 42
Not Completed 2 10 2
Reason Not Completed
Adverse Event             0             7             1
Particpant withdrew consent             0             3             1
Protocol Violation             2             0             0
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo Total
Hide Arm/Group Description For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose. For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose. Participants received matching placebo tablets in the same way as aripiprazole. Total of all reporting groups
Overall Number of Baseline Participants 44 45 44 133
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 45 participants 44 participants 133 participants
11.1  (3.1) 11.8  (2.8) 11.6  (2.8) 11.5  (2.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 44 participants 133 participants
Female
8
  18.2%
10
  22.2%
11
  25.0%
29
  21.8%
Male
36
  81.8%
35
  77.8%
33
  75.0%
104
  78.2%
1.Primary Outcome
Title Change From Baseline to Week 8 in Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS).
Hide Description The YGTSS is a semi-structured clinical interview designed to measure current (time frame of the past 1 week) tic severity. This scale consists of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. 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 primary outcome measure in this trial. The YGTSS ranking of impairment score rated on a 50-point scale anchored from 0 (no impairment) to 50 (severe impairment) to assess impairment experienced in areas of self-esteem, family life, social acceptance, and school scores. This is a fully validated scale in adults and has become a standard instrument for the evaluation of the severity of TD in children.
Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: All participants randomly assigned to the double-blind treatment. At Week 8, data were available for 42 participants in the low dose, 35 in the high dose and 42 in the placebo group.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description:
For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
Participants received matching placebo tablets in the same way as aripiprazole.
Overall Number of Participants Analyzed 42 35 42
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-13.35  (1.59) -16.94  (1.61) -7.09  (1.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments Assuming 5% of participants may drop out of the trial without a postbaseline efficacy evaluation, a total of 126 participants were required to provide at least 80% power to detect a treatment difference of -5 (common standard deviation [SD] of 8.5) between at least 1 of 2 aripiprazole dose levels and placebo in the primary outcome.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments The Hochberg procedure was used to adjust for multiplicity.
Method Mixed Models Analysis
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -6.26
Confidence Interval (2-Sided) 95%
-10.18 to -2.34
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments Assuming 5% of participants may drop out of the trial without a postbaseline efficacy evaluation, a total of 126 participants were required to provide at least 80% power to detect a treatment difference of -5 (common standard SD of 8.5) between at least 1 of 2 aripiprazole dose levels and placebo in the primary outcome.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The Hochberg procedure was used to adjust for multiplicity.
Method Mixed Models Analysis
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -9.85
Confidence Interval (2-Sided) 95%
-13.84 to -5.86
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 8.
Hide Description To assess CGI-TS severity, the rater or physician answered 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 was limited to manifestations of TD only. 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. The change score was obtained from CGI-TS improvement scale assessment: 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 Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All participants randomly assigned to the double-blind treatment. At Week 8, data were available for 42 participants in the low dose, 35 in the high dose and 42 in the placebo group.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description:
For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
Participants received matching placebo tablets in the same way as aripiprazole.
Overall Number of Participants Analyzed 42 35 42
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
2.12  (0.21) 2.13  (0.21) 3.15  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments The Hochberg procedure was used to adjust for multiplicity.
Method Mixed Models Analysis
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-1.54 to -0.52
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The Hochberg procedure was used to adjust for multiplicity.
Method Mixed Models Analysis
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.54 to -0.49
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline to Endpoint (Week 8) in Total YGTSS Score
Hide 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) of motor and vocal tics, and an impairment ranking. The Total YGTSS score is the summation of the severity scores of motor and vocal tics and also the ranking of impairment (range of 0 to 100). A missing value of a YGTSS item scale could result in a missing Total YGTSS score. A reduction in Total YGTSS score from baseline represents an improvement in symptoms.
Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All participants randomly assigned to the double-blind treatment. At Week 8, data were available for 42 participants in the low dose, 35 in the high dose and 42 in the placebo group.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description:
For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
Participants received matching placebo tablets in the same way as aripiprazole.
Overall Number of Participants Analyzed 42 35 42
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-26.69  (3.34) -32.80  (3.39) -13.43  (3.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -13.26
Confidence Interval (2-Sided) 95%
-21.43 to -5.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -19.37
Confidence Interval (2-Sided) 95%
-27.70 to -11.04
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline to Endpoint (Week 8) in CGI-TS Severity Score
Hide Description The CGI-TS Severity scale (range 0-7) is a single-item rating score, with higher scores representing greater severity or less improvement. A response of 0 (not assessed) is considered and handled as missing data.
Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All participants randomly assigned to the double-blind treatment. At Week 8, data were available for 42 participants in the low dose, 35 in the high dose and 42 in the placebo group.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description:
For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
Participants received matching placebo tablets in the same way as aripiprazole.
Overall Number of Participants Analyzed 42 35 42
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-1.35  (0.19) -1.47  (0.19) -0.55  (0.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.80
Confidence Interval (2-Sided) 95%
-1.27 to -0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Treatment, week, treatment by week interaction, region, and weight group were fixed categorical effects; baseline value as a fixed covariate.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-1.41 to -0.44
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Response Rate
Hide Description Clinical response is defined as > 25% improvement from baseline to Week 8 in YGTSS TTS or a CGI-TS Change score of 1 [very much improved] or 2 [much improved] at Week 8. Response will be considered as missing only if both YGTSS TTS and CGI-TS change score are missing. As long as one of them is non-missing, response outcome will be determined based on the non-missing score.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All participants randomly assigned to the double-blind treatment. At Week 8, data were available for 42 participants in the low dose, 35 in the high dose and 42 in the placebo group.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description:
For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
Participants received matching placebo tablets in the same way as aripiprazole.
Overall Number of Participants Analyzed 42 35 42
Measure Type: Number
Unit of Measure: Percentage of Responders
73.8 88.6 54.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0835
Comments P-value derived from Cochran-Mantel-Haenszel (CMH) General Association Test adjusting for region and weight group.
Method Cochran-Mantel-Haenszel
Comments Response ratio > 1 favors aripiprazole.
Method of Estimation Estimation Parameter Response ratio
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
0.98 to 1.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments P-value derived from CMH General Association Test adjusting for region and weight group.
Method Cochran-Mantel-Haenszel
Comments Response ratio > 1 favors aripiprazole.
Method of Estimation Estimation Parameter Response ratio
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
1.20 to 2.16
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Treatment Discontinuation Rate
Hide Description Treatment discontinuation rate will be calculated as the number of discontinued participants (ie, those who were withdrawn from the trial without completing the Week 8 visit) over the number of all randomized participants.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population: All participants randomly assigned to the double-blind treatment.
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description:
For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose.
Participants received matching placebo tablets in the same way as aripiprazole.
Overall Number of Participants Analyzed 44 45 44
Measure Type: Number
Unit of Measure: Percentage of participants
4.5 22.5 4.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9187
Comments Discontinuation ratio < 1 favors aripiprazole. P-value derived from CMH General Association Test adjusting for region and weight group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Discontinuation ratio
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.19 to 7.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole Low Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9576
Comments Hazard ratio < 1 favors aripiprazole. P-value derived from Cox proportional hazard regression adjusting for region and weight group.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0132
Comments Discontinuation ratio < 1 favors aripiprazole. P-value derived from CMH General Association Test adjusting for region and weight group.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Discontinuation ratio
Estimated Value 4.06
Confidence Interval (2-Sided) 95%
1.10 to 14.95
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Aripiprazole High Dose, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0278
Comments Hazard ratio < 1 favors aripiprazole. P-value derived from Cox proportional hazard regression adjusting for region and weight group.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 5.51
Estimation Comments [Not Specified]
Time Frame Adverse events (AEs) were recorded from the time of signing the informed consent up to 30 days after the last trial visit.
Adverse Event Reporting Description An AE is defined as any untoward medical occurrence with the use of study drug. AE was considered serious if fatal, life threatening, disabling or incapacitating, required in participant hospitalization or prolonged hospitalization, congenital anomaly/birth defect or other medically significant event.
 
Arm/Group Title Aripiprazole Low Dose Aripiprazole High Dose Placebo
Hide Arm/Group Description For participants who weighed < 50 kg at baseline, low dose was 5 mg/day. For participants who weighed ≥ 50 kg at baseline, low dose was 10 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was titrated to achieve the randomized dose. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose. For participants who weighed < 50 kg at baseline, high dose was 10 mg/day. For participants who weighed ≥ 50 kg at baseline, high dose was 20 mg/day. All participants randomized to aripiprazole began treatment at 2 mg/day, with the dose titrated to 5 mg/day after 2 days. The dose was then titrated weekly until the randomized dose was achieved. All participants were to have reached their randomized dose by Week 3 (Day 21) and were to remain on that dose. Participants received matching placebo tablets in the same way as aripiprazole.
All-Cause Mortality
Aripiprazole Low Dose Aripiprazole High Dose Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aripiprazole Low Dose Aripiprazole High Dose Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/45 (0.00%)   0/44 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aripiprazole Low Dose Aripiprazole High Dose Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/44 (47.73%)   29/45 (64.44%)   8/44 (18.18%) 
Gastrointestinal disorders       
Nausea * 1  3/44 (6.82%)  4/45 (8.89%)  1/44 (2.27%) 
Vomiting * 1  2/44 (4.55%)  3/45 (6.67%)  2/44 (4.55%) 
General disorders       
Fatigue * 1  3/44 (6.82%)  7/45 (15.56%)  0/44 (0.00%) 
Infections and infestations       
Nasopharyngitis * 1  3/44 (6.82%)  4/45 (8.89%)  0/44 (0.00%) 
Upper respiratory tract infection * 1  1/44 (2.27%)  1/45 (2.22%)  3/44 (6.82%) 
Metabolism and nutrition disorders       
Increased appetite * 1  4/44 (9.09%)  3/45 (6.67%)  1/44 (2.27%) 
Nervous system disorders       
Akathisia * 1  0/44 (0.00%)  3/45 (6.67%)  0/44 (0.00%) 
Headache * 1  3/44 (6.82%)  4/45 (8.89%)  1/44 (2.27%) 
Lethargy * 1  0/44 (0.00%)  5/45 (11.11%)  0/44 (0.00%) 
Sedation * 1  8/44 (18.18%)  4/45 (8.89%)  1/44 (2.27%) 
Somnolence * 1  5/44 (11.36%)  7/45 (15.56%)  1/44 (2.27%) 
Psychiatric disorders       
Restlessness * 1  0/44 (0.00%)  3/45 (6.67%)  1/44 (2.27%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 16.0
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.
Results Point of Contact
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800 562-3974
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01727700     History of Changes
Other Study ID Numbers: 31-12-293
First Submitted: November 12, 2012
First Posted: November 16, 2012
Results First Submitted: January 9, 2015
Results First Posted: February 13, 2015
Last Update Posted: February 13, 2015