Aripiprazole in Children and Adolescents With Bipolar I Disorder

This study has been completed.
Sponsor:
Information provided by:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00110461
First received: May 9, 2005
Last updated: April 19, 2012
Last verified: April 2012
Results First Received: August 11, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Bipolar Disorder
Interventions: Drug: Aripiprazole
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from 59 centers in the United States between March 2005 and February 2007. A total of 413 subjects were screened for enrollment, with 296 subjects assigned to double-blind treatment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were screened over a 28-day period.

Reporting Groups
  Description
Aripiprazole 10 mg/Day Dose was titrated to a target dose of 10 mg/day as follows: Starting dose 2 mg/day, increased to 5 mg/day on Day 3, 10 mg/day on Day 5. One dose reduction to 5 mg/day was allowed in the extension phase. Following a dose reduction, the dose could be up titrated to 10 mg/day if needed.
Aripiprazole 30 mg/Day Dose was titrated to a target dose of 30 mg/day as follows: Starting dose 2 mg/day, increased to 5 mg/day on Day 3, 10 mg/day on Day 5, 15 mg/day on Day 7, 20 mg/day on Day 9, 25 mg/day on Day 11, and 30 mg/day on Day 13. One dose reduction to 15 mg/day was allowed in the extension phase. Following a dose reduction, the dose could be up titrated to 20 mg/day if needed.
Placebo Participants were given a single pill administered once daily.

Participant Flow for 2 periods

Period 1:   30-Week, Double-blind Treatment Phase
    Aripiprazole 10 mg/Day     Aripiprazole 30 mg/Day     Placebo  
STARTED     98     99     99  
COMPLETED     34     22     12  
NOT COMPLETED     64     77     87  

Period 2:   Acute Phase
    Aripiprazole 10 mg/Day     Aripiprazole 30 mg/Day     Placebo  
STARTED     98     99     99  
COMPLETED     84     77     76  
NOT COMPLETED     14     22     23  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Aripiprazole 10 mg/Day Dose was titrated to a target dose of 10 mg/day as follows: Starting dose 2 mg/day, increased to 5 mg/day on Day 3, 10 mg/day on Day 5. One dose reduction to 5 mg/day was allowed in the extension phase. Following a dose reduction, the dose could be up titrated to 10 mg/day if needed.
Aripiprazole 30 mg/Day Dose was titrated to a target dose of 30 mg/day as follows: Starting dose 2 mg/day, increased to 5 mg/day on Day 3, 10 mg/day on Day 5, 15 mg/day on Day 7, 20 mg/day on Day 9, 25 mg/day on Day 11, and 30 mg/day on Day 13. One dose reduction to 15 mg/day was allowed in the extension phase. Following a dose reduction, the dose could be up titrated to 20 mg/day if needed.
Placebo Participants were given a single pill administered once daily.
Total Total of all reporting groups

Baseline Measures
    Aripiprazole 10 mg/Day     Aripiprazole 30 mg/Day     Placebo     Total  
Number of Participants  
[units: participants]
  98     99     99     296  
Age  
[units: years]
Mean ± Standard Deviation
  13.70  ± 2.17     13.31  ± 2.32     13.28  ± 2.12     13.43  ± 2.21  
Gender  
[units: participants]
       
Female     46     48     43     137  
Male     52     51     56     159  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     6     10     15     31  
Not Hispanic or Latino     92     89     84     265  
Unknown or Not Reported     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     0     0     0     0  
Native Hawaiian or Other Pacific Islander     2     0     0     2  
Black or African American     24     18     23     65  
White     65     68     60     193  
More than one race     2     2     2     6  
Unknown or Not Reported     5     11     14     30  
Height  
[units: centimeters¬†(cm)]
Mean ± Standard Deviation
  161.05  ± 12.45     158.37  ± 12.21     158.69  ± 11.63     159.36  ± 12.12  
Weight  
[units: kilograms¬†(kg)]
Mean ± Standard Deviation
  63.76  ± 20.11     60.49  ± 21.50     60.48  ± 17.31     61.57  ± 19.71  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  24.15  ± 5.37     23.66  ± 6.70     23.68  ± 4.98     23.83  ± 5.72  
Young Mania Rating Scale Score (Y-MRS) [1]
[units: points]
Mean ± Standard Deviation
  29.8  ± 6.5     29.5  ± 6.3     30.7  ± 6.8     30.0  ± 6.5  
Children's Depression Rating Scale - Revised (CDRS-R) Suicidal Ideation Score [2]
[units: points]
Mean ± Standard Deviation
  1.1  ± 0.4     1.1  ± 0.5     1.2  ± 0.5     1.2  ± 0.5  
Treatment given for previous episodes  
[units: participants]
       
Yes     57     50     63     170  
No     41     49     36     126  
[1] The Y-MRS consists of 11 items assessing the core symptoms of mania. Each item has 5 defined grades of severity. Minimum score on the scale is 0 (absent or normal); maximum score on the scale is 60 (worse outcome or more severe symptoms).
[2] The CDRS-R is used to diagnose depression and monitor treatment response. The interviewer rates 17 symptom areas (including those that sever as DSM-IV criteria for diagnosis of depression), among them suicidal ideation. Most of the 17 symptom areas are rated on a 7-point scale. The Suicide Ideation Score is rated on a 7-point scale, where the minimum score on the scale is 1 (better outcome) and the maximum score is 7 (worse outcome).



  Outcome Measures
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1.  Primary:   Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 4   [ Time Frame: Baseline and Week 4 ]

2.  Secondary:   Change in Young Mania Rating Scale (Y-MRS) Total Score at Week 30   [ Time Frame: Baseline and Week 30 ]

3.  Secondary:   Change in Children’s Global Assessment Scale (CGAS) Total Score at Week 4   [ Time Frame: Baseline and Week 4 ]

4.  Secondary:   Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4   [ Time Frame: Baseline and Week 4 ]

5.  Secondary:   Change in Children’s Depression Rating Scale-Revised (CDRS-R) Total Score at Week 4   [ Time Frame: Baseline and Week 4 ]

6.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 4   [ Time Frame: Baseline and Week 4 ]

7.  Secondary:   Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 4   [ Time Frame: Baseline and Week 4 ]

8.  Secondary:   Change in Children's Global Assessment (CGAS) Total Score at Week 30   [ Time Frame: Baseline and Week 30 ]

9.  Secondary:   Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30   [ Time Frame: Baseline and Week 30 ]

10.  Secondary:   Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4   [ Time Frame: Baseline and Week 4 ]

11.  Secondary:   Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30   [ Time Frame: Baseline and Week 30 ]

12.  Secondary:   Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4   [ Time Frame: Baseline and Week 4 ]

13.  Secondary:   Change in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30   [ Time Frame: Baseline and Week 30 ]

14.  Secondary:   Change in Children's Depression Rating Scale-Revised (CDRS-R) Total Score at Week 30   [ Time Frame: Baseline and Week 30 ]

15.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Mania Score at Week 30   [ Time Frame: Baseline and Week 30 ]

16.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 4   [ Time Frame: Baseline and Week 4 ]

17.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Subject Version Mania Score at Week 30   [ Time Frame: Baseline and Week 30 ]

18.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 4   [ Time Frame: Baseline and Week 4 ]

19.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Parent/Guardian Version Depression Score at Week 30   [ Time Frame: Baseline and Week 30 ]

20.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 4   [ Time Frame: Baseline and Week 4 ]

21.  Secondary:   Change in General Behavior Inventory Scale (GBI) Total Subject Version Depression Score at Week 30   [ Time Frame: Baseline and Week 30 ]

22.  Secondary:   Change in Attention Deficit Hyperactivity Disorders Rating Scale (ADHD-RS-IV) Total Score at Week 30   [ Time Frame: Baseline and Week 30 ]

23.  Secondary:   Subject Response to Treatment at Week 4   [ Time Frame: Baseline and Week 4 ]

24.  Secondary:   Subject Response to Treatment at Week 30   [ Time Frame: Baseline and Week 30 ]

25.  Secondary:   Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 4   [ Time Frame: Baseline and Week 4 ]

26.  Secondary:   Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Mania Score at Week 30   [ Time Frame: Baseline and Week 30 ]

27.  Secondary:   Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 4   [ Time Frame: Baseline and Week 4 ]

28.  Secondary:   Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Depression Score at Week 30   [ Time Frame: Baseline and Week 30 ]

29.  Secondary:   Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 4   [ Time Frame: Baseline and Week 4 ]

30.  Secondary:   Change From Previous Phase in Clinical Global Impressions Scale-Bipolar Version (CGI-BP) Severity Overall Illness Score at Week 30   [ Time Frame: Baseline and Week 30 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Primary efficacy endpoint is change from baseline in Y-MRS total score. Only randomized subjects with both baseline and 1+ post-baseline were included in primary efficacy analysis so # randomized is different from # included in the efficacy analysis.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Andy Forbes
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
e-mail: andy.forbes@otsuka-us.com


No publications provided by Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications automatically indexed to this study:

Responsible Party: Arifulla Khan, MD, Northwest Clinical Research Center
ClinicalTrials.gov Identifier: NCT00110461     History of Changes
Other Study ID Numbers: 31-03-240
Study First Received: May 9, 2005
Results First Received: August 11, 2011
Last Updated: April 19, 2012
Health Authority: United States: Food and Drug Administration