A Short Treatment Study of Aripiprazole in Pediatric Patients With Schizophrenia

A Multicenter, Double-blind, Randomized, Dose-comparison Study of Three Different Doses of Aripiprazole (2 mg/Day, 6-12 mg/Day, 24-30 mg/Day) Orally Administered Over 6 Weeks in Pediatric Patients (Aged 13-17 Years) With Schizophrenia

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Aripiprazole Low (2 mg/day); Drug: Aripiprazole Mid (6 - 12 mg/day); Drug: Aripiprazole High (24 - 30 mg/day)

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chubu Region, Japan
  • Chugoku Region, Japan
  • Hokkaido Region, Japan
  • Kansai Region, Japan
  • Kanto Region, Japan
  • Kyushu Region, Japan
  • Shikoku Region, Japan
  • Tohoku Region, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low (2 mg/day); Subjects in the 2 mg/day group will be administered 2 mg once daily for 6 weeks (42 days).	Drug: Aripiprazole Low (2 mg/day); administered 2 mg once daily for 6 weeks; Other Names: Aripiprazole
Experimental: 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.	Drug: 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; Other Names: Aripiprazole
Experimental: 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.	Drug: 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; Other Names: Aripiprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) and Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) and Day 43
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.	Baseline (Day 1) and Day43
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.	Baseline (Day 1) and day43
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.	Baseline (Day 1) and Day 43

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: September 10, 2013
• First Submitted That Met QC Criteria: September 12, 2013
• First Posted (Estimate): September 13, 2013

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Schyzophrenia, pediatric patients
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: 031-09-003; JapicCTI-101146 (Other Identifier: JAPIC)