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Aripiprazole in Adolescents With Schizophrenia (APEX 239)

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: NCT00102063
Recruitment Status : Completed
First Posted : January 20, 2005
Results First Posted : August 1, 2012
Last Update Posted : August 10, 2012
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
Condition Schizophrenia
Interventions Drug: Aripiprazole tablet, 10 mg
Drug: Aripiprazole tablet, 30 mg
Drug: Placebo tablet
Enrollment 302
Recruitment Details Participants were recruited from 101 centers in the United States, Europe, South America, the Caribbean, and South Africa between August 2004 and August 2006.
Pre-assignment Details Participants were screened over a 4-week period.
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description 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 allowed after Day 25 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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25 Participants were given a single pill administered once daily
Period Title: Overall Study
Started 100 102 100
Completed 84 84 90
Not Completed 16 18 10
Reason Not Completed
Lack of Efficacy             5             1             1
Adverse Event             7             4             2
Withdrawal by Subject             4             12             5
Lost to Follow-up             0             0             1
Protocol Violation             0             1             1
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group Total
Hide Arm/Group Description 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 allowed after Day 25 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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25 Participants were given a single pill administered once daily Total of all reporting groups
Overall Number of Baseline Participants 100 102 100 302
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants 102 participants 100 participants 302 participants
15.6  (1.3) 15.4  (1.4) 15.4  (1.4) 15.5  (1.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 102 participants 100 participants 302 participants
Female
55
  55.0%
37
  36.3%
39
  39.0%
131
  43.4%
Male
45
  45.0%
65
  63.7%
61
  61.0%
171
  56.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 102 participants 100 participants 302 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   1.0%
1
   0.3%
Asian
16
  16.0%
12
  11.8%
15
  15.0%
43
  14.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
17
  17.0%
11
  10.8%
6
   6.0%
34
  11.3%
White
54
  54.0%
62
  60.8%
64
  64.0%
180
  59.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
13
  13.0%
17
  16.7%
14
  14.0%
44
  14.6%
1.Primary Outcome
Title Change in Positive and Negative Syndrome Scale (PANSS) Total Score
Hide Description

Change from baseline to last observed post-baseline value in PANSS total score, using the last observation carried forward.

This scale consists of symptom constructs (7 positive, 7 negative, 16 general psychopathology), each to be rated on a 7-point scale of severity with 1 being absent to 7 being extreme. Minimum score is 30 which is best outcome; maximum score is 210 for worse outcome.

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Mean (Standard Error)
Unit of Measure: points
-26.7  (1.9) -28.6  (0.9) -21.2  (1.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Aripiprazole 10 mg/Day Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Aripiprazole 30 mg/Day Group, Placebo Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Change in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score
Hide Description

Change from baseline to last observed post-baseline value in PANSS positive subscale score, using the last observation carried forward.

Scale consists of 7 positive symptom constructs each to be rated on a 7- point scale of severity with 1 = absent to 7 = extreme. Minimum score is 7 which is best outcome; maximum score is 49 for worse outcome.

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 98 99 97
Mean (Standard Error)
Unit of Measure: points
-7.6  (0.6) -8.1  (0.6) -5.6  (0.6)
3.Secondary Outcome
Title Change in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score
Hide Description

Change from baseline to last observed post-baseline value in PANSS Negative Subscale score, using the last observation carried forward.

Scale consists of 7 negative symptom constructs each to be rated on a 7- point scale of severity with 1 = absent to 7 = extreme. Minimum score is 7 which is best outcome; maximum score is 49 for worse outcome.

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Mean (Standard Error)
Unit of Measure: points
-6.9  (0.6) -6.6  (0.6) -5.4  (0.6)
4.Secondary Outcome
Title Change in Clinical Global Impression (CGI) Severity Score
Hide Description

Change from baseline to last observed post-baseline value in CGI severity score, using the last observation carried forward.

Scale refers to the global impression of the subject with respect to severity of the illness. The scale rates the subject's severity of illness from 0 (not rated) to 1 (least severe) to 7 (most severe).

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Mean (Standard Error)
Unit of Measure: points
-1.2  (0.1) -1.3  (0.1) -0.9  (0.1)
5.Secondary Outcome
Title Clinical Global Impression (CGI) Improvement Score
Hide Description

Last observed post-baseline value in CGI improvement score, using the last observation carried forward.

Scale refers to the global impression of the subject with respect to improvement of the illness. The scale rates the subject's severity of illness from 0 (not rated) to 1 (least severe) to 7 (most severe).

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Mean (Standard Error)
Unit of Measure: points
2.7  (0.1) 2.5  (0.1) 3.1  (0.1)
6.Secondary Outcome
Title Change in Children’s Global Assessment Scale (CGAS) Score
Hide Description

Change from baseline to last observed post-baseline value in CGAS score, using the last observation carried forward.

Scale is a 100-point scale measuring psychological, social, and school functioning for children aged 6 to 17 years. Minimum scores ranged from 1-10, representing the need for constant supervision (worse outcome) to maximum scores of 91-100, representing superior functioning (better outcome).

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Mean (Standard Error)
Unit of Measure: points
14.7  (1.5) 14.8  (1.3) 9.8  (1.3)
7.Other Pre-specified Outcome
Title Change in Pediatric Quality of Life Enjoyment and Satisfaction (PQLES) Questionnaire Total Score
Hide Description

Change from baseline to last observed post-baseline value in PQLES total score, using the last observation carried forward.

Scale consists of 14 items pertaining to daily life activities and satisfaction, and an overall assessment item. Each item will be rated on a five-point scale (1=very poor, 2=poor, 3=fair, 4=good, 5=very good) with a minimum score of 14 (better outcome) and a maximum score of 70 (worse outcome).

Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Mean (Standard Error)
Unit of Measure: points
5.2  (0.9) 5.9  (0.9) 4.5  (0.9)
8.Other Pre-specified Outcome
Title Patients Achieving Remission
Hide Description The number of subjects achieving remission. Remission was defined as a score of mild or less (≤ 3) for items P1, P2, P3, N1, N4, N6, G5, and G9 in the PANSS score.
Time Frame Baseline and Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description:
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 allowed after Day 25
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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25
Participants were given a single pill administered once daily
Overall Number of Participants Analyzed 99 97 98
Measure Type: Number
Unit of Measure: participants
53 56 35
Time Frame Adverse event data were collected as spontaneous reports at all scheduled visits. Serious AEs were monitored until the subject’s health returned to baseline status or other parameters returned to normal or were otherwise explained.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Hide Arm/Group Description 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 allowed after Day 25 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, and 30 mg/day on Day 11; one dose reduction to 15 mg/day allowed after Day 25 Participants were given a single pill administered once daily
All-Cause Mortality
Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/100 (4.00%)   4/102 (3.92%)   3/100 (3.00%) 
Infections and infestations       
Varicella * 1  0/100 (0.00%)  1/102 (0.98%)  0/100 (0.00%) 
Injury, poisoning and procedural complications       
Intentional overdose * 1  0/100 (0.00%)  0/102 (0.00%)  1/100 (1.00%) 
Overdose * 1  0/100 (0.00%)  0/102 (0.00%)  1/100 (1.00%) 
Nervous system disorders       
Extrapyramidal disorder * 1  1/100 (1.00%)  0/102 (0.00%)  0/100 (0.00%) 
Neuroleptic malignant syndrome * 1 [1]  1/100 (1.00%)  0/102 (0.00%)  0/100 (0.00%) 
Psychiatric disorders       
Aggression * 1  1/100 (1.00%)  0/102 (0.00%)  0/100 (0.00%) 
Depression * 1  0/100 (0.00%)  1/102 (0.98%)  0/100 (0.00%) 
Psychotic disorder * 1  1/100 (1.00%)  1/102 (0.98%)  1/100 (1.00%) 
Schizophrenia * 1  1/100 (1.00%)  1/102 (0.98%)  0/100 (0.00%) 
Suicidal ideation * 1  0/100 (0.00%)  1/102 (0.98%)  0/100 (0.00%) 
Suicide attempt * 1  0/100 (0.00%)  0/102 (0.00%)  1/100 (1.00%) 
Vascular disorders       
Thrombophlebitis * 1  0/100 (0.00%)  1/102 (0.98%)  0/100 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.1)
[1]
Event did not meet the criteria for neuroleptic syndrome
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aripiprazole 10 mg/Day Group Aripiprazole 30 mg/Day Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   71/100 (71.00%)   74/102 (72.55%)   57/100 (57.00%) 
Gastrointestinal disorders       
Nausea * 1  9/100 (9.00%)  10/102 (9.80%)  6/100 (6.00%) 
Vomiting * 1  5/100 (5.00%)  3/102 (2.94%)  5/100 (5.00%) 
Infections and infestations       
Nasopharyngitis * 1  5/100 (5.00%)  5/102 (4.90%)  4/100 (4.00%) 
Nervous system disorders       
Akathisia * 1  5/100 (5.00%)  5/102 (4.90%)  12/100 (12.00%) 
Dizziness * 1  7/100 (7.00%)  4/102 (3.92%)  3/100 (3.00%) 
Extrapyramidal disorder * 1  13/100 (13.00%)  22/102 (21.57%)  5/100 (5.00%) 
Headache * 1  16/100 (16.00%)  11/102 (10.78%)  10/100 (10.00%) 
Somnolence * 1  11/100 (11.00%)  22/102 (21.57%)  6/100 (6.00%) 
Tremor * 1  2/100 (2.00%)  12/102 (11.76%)  2/100 (2.00%) 
Psychiatric disorders       
Agitation * 1  1/100 (1.00%)  3/102 (2.94%)  5/100 (5.00%) 
Insomnia * 1  11/100 (11.00%)  10/102 (9.80%)  15/100 (15.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (9.1)
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
Layout table for Results Point of Contact information
Name/Title: Margaretta Nyilas
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 609-452-5673
EMail: Margaretta.nyilas@otsuka-us.com
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00102063     History of Changes
Other Study ID Numbers: 31-03-239
First Submitted: January 19, 2005
First Posted: January 20, 2005
Results First Submitted: May 11, 2012
Results First Posted: August 1, 2012
Last Update Posted: August 10, 2012