Schizophrenia
Conditions
Keywords
Schizophrenia, Aripiprazole
Brief summary
The purpose of this trial is to test the safety and efficacy of aripiprazole in adolescent patients with schizophrenia for a period of at least 6 weeks.
Interventions
DRUGAripiprazole tablet, 10 mg
Aripiprazole tablet 10 mg po qd x 42 days
DRUGAripiprazole tablet, 30 mg
Aripiprazole tablet 30 mg po qd x 42 days
DRUGPlacebo tablet
Placebo tablet po qd x 42 days
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Primary diagnosis of Schizophrenia 1
Exclusion criteria
* Patients diagnosed with schizoaffective disorder, major depressive disorder, delirium, or bipolar disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline and Day 42 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score | Baseline and Day 42 | 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. |
| Change in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score | Baseline and Day 42 | 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. |
| Change in Clinical Global Impression (CGI) Severity Score | Baseline and Day 42 | 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). |
| Clinical Global Impression (CGI) Improvement Score | Baseline and Day 42 | 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). |
| Change in Children's Global Assessment Scale (CGAS) Score | Baseline and Day 42 | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Pediatric Quality of Life Enjoyment and Satisfaction (PQLES) Questionnaire Total Score | Baseline and Day 42 | 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). |
| Patients Achieving Remission | Baseline and Day 42 | 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. |
Countries
Puerto Rico, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole 10 mg/Day Group 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 | 100 |
| Aripiprazole 30 mg/Day Group 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 | 102 |
| Placebo Group Participants were given a single pill administered once daily | 100 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 4 | 2 |
| Overall Study | Lack of Efficacy | 5 | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 12 | 5 |
Baseline characteristics
| Characteristic | Aripiprazole 10 mg/Day Group | Aripiprazole 30 mg/Day Group | Placebo Group | Total |
|---|---|---|---|---|
| Age Continuous | 15.6 years STANDARD_DEVIATION 1.3 | 15.4 years STANDARD_DEVIATION 1.4 | 15.4 years STANDARD_DEVIATION 1.4 | 15.5 years STANDARD_DEVIATION 1.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 12 Participants | 15 Participants | 43 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 11 Participants | 6 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants | 17 Participants | 14 Participants | 44 Participants |
| Race (NIH/OMB) White | 54 Participants | 62 Participants | 64 Participants | 180 Participants |
| Sex: Female, Male Female | 55 Participants | 37 Participants | 39 Participants | 131 Participants |
| Sex: Female, Male Male | 45 Participants | 65 Participants | 61 Participants | 171 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 71 / 100 | 74 / 102 | 57 / 100 |
| serious Total, serious adverse events | 4 / 100 | 4 / 102 | 3 / 100 |
Outcome results
Primary
Change in Positive and Negative Syndrome Scale (PANSS) Total Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Change in Positive and Negative Syndrome Scale (PANSS) Total Score | -26.7 points | Standard Error 1.9 |
| Aripiprazole 30 mg/Day Group | Change in Positive and Negative Syndrome Scale (PANSS) Total Score | -28.6 points | Standard Error 0.9 |
| Placebo Group | Change in Positive and Negative Syndrome Scale (PANSS) Total Score | -21.2 points | Standard Error 1.9 |
p-value: 0.05t-test, 2 sided
p-value: 0.007t-test, 2 sided
Secondary
Change in Children's Global Assessment Scale (CGAS) Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Change in Children's Global Assessment Scale (CGAS) Score | 14.7 points | Standard Error 1.5 |
| Aripiprazole 30 mg/Day Group | Change in Children's Global Assessment Scale (CGAS) Score | 14.8 points | Standard Error 1.3 |
| Placebo Group | Change in Children's Global Assessment Scale (CGAS) Score | 9.8 points | Standard Error 1.3 |
Secondary
Change in Clinical Global Impression (CGI) Severity Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Change in Clinical Global Impression (CGI) Severity Score | -1.2 points | Standard Error 0.1 |
| Aripiprazole 30 mg/Day Group | Change in Clinical Global Impression (CGI) Severity Score | -1.3 points | Standard Error 0.1 |
| Placebo Group | Change in Clinical Global Impression (CGI) Severity Score | -0.9 points | Standard Error 0.1 |
Secondary
Change in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Change in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score | -6.9 points | Standard Error 0.6 |
| Aripiprazole 30 mg/Day Group | Change in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score | -6.6 points | Standard Error 0.6 |
| Placebo Group | Change in Positive and Negative Syndrome Scale (PANSS) Negative Subscale Score | -5.4 points | Standard Error 0.6 |
Secondary
Change in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Change in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score | -7.6 points | Standard Error 0.6 |
| Aripiprazole 30 mg/Day Group | Change in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score | -8.1 points | Standard Error 0.6 |
| Placebo Group | Change in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Score | -5.6 points | Standard Error 0.6 |
Secondary
Clinical Global Impression (CGI) Improvement Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Clinical Global Impression (CGI) Improvement Score | 2.7 points | Standard Error 0.1 |
| Aripiprazole 30 mg/Day Group | Clinical Global Impression (CGI) Improvement Score | 2.5 points | Standard Error 0.1 |
| Placebo Group | Clinical Global Impression (CGI) Improvement Score | 3.1 points | Standard Error 0.1 |
Other Pre-specified
Change in Pediatric Quality of Life Enjoyment and Satisfaction (PQLES) Questionnaire Total Score
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole 10 mg/Day Group | Change in Pediatric Quality of Life Enjoyment and Satisfaction (PQLES) Questionnaire Total Score | 5.2 points | Standard Error 0.9 |
| Aripiprazole 30 mg/Day Group | Change in Pediatric Quality of Life Enjoyment and Satisfaction (PQLES) Questionnaire Total Score | 5.9 points | Standard Error 0.9 |
| Placebo Group | Change in Pediatric Quality of Life Enjoyment and Satisfaction (PQLES) Questionnaire Total Score | 4.5 points | Standard Error 0.9 |
Other Pre-specified
Patients Achieving Remission
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aripiprazole 10 mg/Day Group | Patients Achieving Remission | 53 participants |
| Aripiprazole 30 mg/Day Group | Patients Achieving Remission | 56 participants |
| Placebo Group | Patients Achieving Remission | 35 participants |