Schizophrenia
Conditions
Keywords
Schyzophrenia, pediatric patients
Brief summary
The objective of this study is to investigate the efficacy and safety of three different doses of aripiprazole (2 mg/day, 6-12 mg/day, 24-30 mg/day) orally administered over a period of 6 weeks in pediatric patients (aged 13-17 years) with schizophrenia
Interventions
DRUGAripiprazole Low (2 mg/day)
administered 2 mg once daily for 6 weeks
DRUGAripiprazole Mid (6 - 12 mg/day)
administered 2 mg once daily for 2 days, followed by a maintenance dose of 6 mg for 40 days. From Day 15 onwards, the dose may be increased to 12 mg
DRUGAripiprazole High (24 - 30 mg/day)
administered 2, 6, 12, 18 mg sequentially, each dose once daily for 2 days respectively, followed by a maintenance dose of 24 mg for 34 days. From Day 15 onwards, the dose may be increased to 30 mg
Sponsors
Otsuka Pharmaceutical Co., Ltd.
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
* Patients with a diagnosis of schizophrenia (295.30, 295.10, 295.20, 295.90, 295.60), according to DSM-Ⅳ-TR (M.I.N.I.KID will be used as backup) * Male and female patients aged 13-17 years (between IC and end of dosing) * Patients with a PANSS score of 70 or more \[both at start of dosing (Day 1 and at baseline * Patients who, in addition to their legal guardian, provide written informed consent, having understood the details of this study * Inpatient or outpatient status
Exclusion criteria
* Patients who have a diagnosis of any other disease except schizophrenia, according to DSM-IV-TR * Patients who have been compulsorily admitted to hospital * Patients with mental retardation * Patients with thyroid disorder * Patients who have a history of receiving treatment with clozapine, or who have received sufficient doses of two or more kinds of antipsychotic drug for more than four weeks but failed to respond to this treatment * Patients who have received a prohibited concomitant medication or therapy listed in table 6.4-1 after the start of the prohibited concomitant medication timeframe \[to be confirmed at start of dosing (Day 1) and at baseline\]. * Patients who have a history of receiving treatment with aripiprazole * Patients who fall under a contraindication listed in the ABILIFY package insert * Patients with a serious hepatic, renal, cardiac or hematopoietic disorder * Patients with a history or a complication of organic brain disorder or convulsive disorder such as epilepsy * Patients with diabetes. and patients who fall under any of the following: fasting blood glucose level ≧126 mg/ｄL, non-fasting blood glucose level ≧200 mg/dL, HbA1c≧6.5% * Patients with a history or a complication of suicide attempt, suicidal thought or self-harm * Patients with a score of ≧2(mild) on PART1 evaluation of CGI-SS * Patients with a history or a complication of malignant syndrome, tardive dyskinesia or paralytic ileus * Patients in a state of physical exhaustion accompanied by such conditions as dehydration or malnutrition * Patients with a history or a complication of water intoxication * Patients with Parkinson's disease * Pregnant women, parturient women, nursing women, women of childbearing potential who wish to become pregnant during this trial. However, women of childbearing potential who are practicing an appropriate method of contraception and have a negative pregnancy test result are eligible for inclusion in this study. * Patients who have a diagnosis of a substance-related disorder according to DSM-Ⅳ-TR within the past 3 months * Patients with a positive drug screen (urine) result * Study enrollment is otherwise judged to be inappropriate by the Investigator or Subinvestigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline (Day 1) and Day 43 | The Positive and Negative Syndrome Scale (PANSS) is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7: 1 =Absent, 2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme. PANSS total score is calculated by adding score of 30 items, which ranges from 30-210. Higher scores indicate worse condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Total Score | Baseline (Day 1) and Day 43 | The Positive and Negative Syndrome Scale (PANSS) positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49, with higher values indicating worse condition. |
| Mean Change From Baseline at Final Assessment in Clinical Global Impression-Severity of Illness (CGI-S) Score | Baseline (Day 1) and Day43 | The Clinical Global Impression-Severity of Illness (CGI-S) Score is a clinician rated scale which assesses how mentally ill the patient is at the time. Scores range from 0 to 7: 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, 7= Among the most extremely ill patients. Higher scores indicate worse condition. |
| Mean Change From Baseline at Final Assessment in Clinical Global Impression-Improvement (CGI-I) Score | Baseline (Day 1) and day43 | The Clinical Global Impression-Improvement (CGI-I) Score is a clinician rated scale which assesses the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition. |
| Mean Change From Baseline at Final Assessment in Children's Global Assessment Scale (C-GAS) Score | Baseline (Day 1) and Day 43 | The Children's Global Assessment Scale (C-GAS) is a rating scale which measures psychological, social and school functioning for children aged 6-17. Scores range from 0 to 100, with higher scores indicating better condition. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low (2 mg/Day) Subjects in the 2 mg/day group will be administered 2 mg once daily for 6 weeks (42 days).
Aripiprazole Low (2 mg/day): administered 2 mg once daily for 6 weeks | 35 |
| Mid (6 - 12 mg/Day) Subjects in the 6-12 mg/day group will be administered 2 mg once daily for 2 days, followed by a maintenance dose of 6 mg for 40 days. From Day 15 onwards, the dose may be increased to 12 mg in accordance with the criteria below.
Aripiprazole Mid (6 - 12 mg/day): administered 2 mg once daily for 2 days, followed by a maintenance dose of 6 mg for 40 days. From Day 15 onwards, the dose may be increased to 12 mg | 30 |
| High (24 - 30 mg/Day) Subjects in the 24-30 mg/day group will be administered 2, 6, 12, 18 mg sequentially, each dose once daily for 2 days respectively, followed by a maintenance dose of 24 mg for 34 days. From Day 15 onwards, the dose may be increased to 30 mg in accordance with the criteria below.
Aripiprazole High (24 - 30 mg/day): administered 2, 6, 12, 18 mg sequentially, each dose once daily for 2 days respectively, followed by a maintenance dose of 24 mg for 34 days. From Day 15 onwards, the dose may be increased to 30 mg | 41 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 5 |
| Overall Study | Physician Decision | 3 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 1 |
Baseline characteristics
| Characteristic | Total | Low (2 mg/Day) | Mid (6 - 12 mg/Day) | High (24 - 30 mg/Day) |
|---|---|---|---|---|
| Age, Categorical <=18 years | 106 Participants | 35 Participants | 30 Participants | 41 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 15.0 years STANDARD_DEVIATION 1.4 | 15.1 years STANDARD_DEVIATION 1.4 | 15.4 years STANDARD_DEVIATION 1.3 | 14.7 years STANDARD_DEVIATION 1.3 |
| Region of Enrollment Japan | 106 participants | 35 participants | 30 participants | 41 participants |
| Sex: Female, Male Female | 55 Participants | 21 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 51 Participants | 14 Participants | 19 Participants | 18 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 | 29 / 35 | 28 / 30 | 38 / 41 |
| serious Total, serious adverse events | 0 / 35 | 2 / 30 | 2 / 41 |
Outcome results
Primary
Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Total Score
The Positive and Negative Syndrome Scale (PANSS) is a 30-item scale where each symptom is rated on a severity scale ranging from 1-7: 1 =Absent, 2 =Minimal, 3 =Mild, 4 =Moderate, 5 =Moderate severe, 6 =Severe, 7= Extreme. PANSS total score is calculated by adding score of 30 items, which ranges from 30-210. Higher scores indicate worse condition.
Time frame: Baseline (Day 1) and Day 43
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low (2 mg/Day) | Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Total Score | -19.6 units on a scale | Standard Error 3.2 |
| Mid (6 - 12 mg/Day) | Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Total Score | -16.5 units on a scale | Standard Error 3.5 |
| High (24 - 30 mg/Day) | Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Total Score | -21.6 units on a scale | Standard Error 3 |
Secondary
Mean Change From Baseline at Final Assessment in Children's Global Assessment Scale (C-GAS) Score
The Children's Global Assessment Scale (C-GAS) is a rating scale which measures psychological, social and school functioning for children aged 6-17. Scores range from 0 to 100, with higher scores indicating better condition.
Time frame: Baseline (Day 1) and Day 43
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low (2 mg/Day) | Mean Change From Baseline at Final Assessment in Children's Global Assessment Scale (C-GAS) Score | 10.5 units on a scale | Standard Error 2 |
| Mid (6 - 12 mg/Day) | Mean Change From Baseline at Final Assessment in Children's Global Assessment Scale (C-GAS) Score | 8.5 units on a scale | Standard Error 2.1 |
| High (24 - 30 mg/Day) | Mean Change From Baseline at Final Assessment in Children's Global Assessment Scale (C-GAS) Score | 8.6 units on a scale | Standard Error 1.8 |
Secondary
Mean Change From Baseline at Final Assessment in Clinical Global Impression-Improvement (CGI-I) Score
The Clinical Global Impression-Improvement (CGI-I) Score is a clinician rated scale which assesses the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition.
Time frame: Baseline (Day 1) and day43
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low (2 mg/Day) | Mean Change From Baseline at Final Assessment in Clinical Global Impression-Improvement (CGI-I) Score | 3.0 units on a scale | Standard Error 0.2 |
| Mid (6 - 12 mg/Day) | Mean Change From Baseline at Final Assessment in Clinical Global Impression-Improvement (CGI-I) Score | 3.2 units on a scale | Standard Error 0.2 |
| High (24 - 30 mg/Day) | Mean Change From Baseline at Final Assessment in Clinical Global Impression-Improvement (CGI-I) Score | 2.7 units on a scale | Standard Error 0.2 |
Secondary
Mean Change From Baseline at Final Assessment in Clinical Global Impression-Severity of Illness (CGI-S) Score
The Clinical Global Impression-Severity of Illness (CGI-S) Score is a clinician rated scale which assesses how mentally ill the patient is at the time. Scores range from 0 to 7: 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, 7= Among the most extremely ill patients. Higher scores indicate worse condition.
Time frame: Baseline (Day 1) and Day43
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low (2 mg/Day) | Mean Change From Baseline at Final Assessment in Clinical Global Impression-Severity of Illness (CGI-S) Score | -0.9 units on a scale | Standard Error 0.2 |
| Mid (6 - 12 mg/Day) | Mean Change From Baseline at Final Assessment in Clinical Global Impression-Severity of Illness (CGI-S) Score | -0.8 units on a scale | Standard Error 0.2 |
| High (24 - 30 mg/Day) | Mean Change From Baseline at Final Assessment in Clinical Global Impression-Severity of Illness (CGI-S) Score | -1.0 units on a scale | Standard Error 0.2 |
Secondary
Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Total Score
The Positive and Negative Syndrome Scale (PANSS) positive subscale score is the sum of the 7 positive item scores (ie, delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution and hostility) and ranges from 7 to 49, with higher values indicating worse condition.
Time frame: Baseline (Day 1) and Day 43
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low (2 mg/Day) | Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Total Score | -5.2 units on a scale | Standard Error 0.8 |
| Mid (6 - 12 mg/Day) | Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Total Score | -4.9 units on a scale | Standard Error 0.9 |
| High (24 - 30 mg/Day) | Mean Change From Baseline at Final Assessment in Positive and Negative Syndrome Scale (PANSS) Positive Subscale Total Score | -5.8 units on a scale | Standard Error 0.8 |