Aripiprazole in Adolescents With Schizophrenia (APEX 239)

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Aripiprazole tablet, 10 mg; Drug: Aripiprazole tablet, 30 mg; Drug: Placebo tablet

• Study Type: Interventional
• Enrollment (Actual): 302
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico
    • Local Institution
  • San Juan, Puerto Rico
    • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Local Institution
  • Arkansas
    • Little Rock, Arkansas, United States
      • Local Institution
  • California
    • Costa Mesa, California, United States
      • Local Institution
    • Los Angeles, California, United States
      • Local Institution
    • National City, California, United States
      • Local Institution
    • Orange, California, United States
      • Local Institution
    • Pasadena, California, United States
      • Local Institution
    • Sacramento, California, United States
      • Local Institution
    • San Diego, California, United States
      • Local Institution
    • Temecula, California, United States
      • Local Institution
  • District of Columbia
    • Washington, District of Columbia, United States
      • Local Institution
  • Florida
    • Altamonte Springs, Florida, United States
      • Local Institution
    • Ft. Lauderdale, Florida, United States
      • Local Institution
    • Gainesville, Florida, United States
      • Local Institution
    • Hialeah, Florida, United States
      • Local Institution
    • Jacksonville, Florida, United States
      • Local Institution
    • Miami, Florida, United States
      • Local Institution
    • North Miami, Florida, United States
      • Local Institution
    • Orange City, Florida, United States
      • Local Institution
    • Tampa, Florida, United States
      • Local Institution
  • Georgia
    • Newnan, Georgia, United States
      • Local Institution
    • Smyrna, Georgia, United States
      • Local Institution
  • Hawaii
    • Honolulu, Hawaii, United States
      • Local Institution
  • Illinois
    • Chicago, Illinois, United States
      • Local Institution
  • Kansas
    • Kansas City, Kansas, United States
      • Local Institution
  • Kentucky
    • Lexington, Kentucky, United States
      • Local Institution
  • Louisiana
    • Lake Charles, Louisiana, United States
      • Local Institution
    • New Orleans, Louisiana, United States
      • Local Institution
  • Massachusetts
    • Medford, Massachusetts, United States
      • Local Institution
  • Michigan
    • Clinton Township, Michigan, United States
      • Local Institution
  • Mississippi
    • Flowood, Mississippi, United States
      • Local Institution
  • Missouri
    • Kansas City, Missouri, United States
      • Local Institution
  • Nevada
    • Las Vegas, Nevada, United States
      • Local Institution
  • New York
    • Elmsford, New York, United States
      • Local Institution
    • New York, New York, United States
      • Local Institution
    • Olean, New York, United States
      • Local Institution
    • Rochester, New York, United States
      • Local Institution
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • Local Institution
  • Ohio
    • Cleveland, Ohio, United States
      • Local Institution
    • Lyndhurst, Ohio, United States
      • Local Institution
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Local Institution
  • Pennsylvania
    • Bala Cynwyd, Pennsylvania, United States
      • Local Institution
    • Philadelphia, Pennsylvania, United States
      • Local Institution
  • Tennessee
    • Memphis, Tennessee, United States
      • Local Institution
  • Texas
    • Bellaire, Texas, United States
      • Local Institution
    • DeSoto, Texas, United States
      • Local Institution
    • Houston, Texas, United States
      • Local Institution
    • San Antonio, Texas, United States
      • Local Institution
  • Utah
    • Salt Lake City, Utah, United States
      • Local Institution
  • Virginia
    • Richmond, Virginia, United States
      • Local Institution
  • Washington
    • Kirkland, Washington, United States
      • Local Institution
    • Spokane, Washington, United States
      • Local Institution
  • Wisconsin
    • Wauwatosa, Wisconsin, United States
      • Local Institution

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:

• Primary diagnosis of Schizophrenia 1

Exclusion Criteria:

• Patients diagnosed with schizoaffective disorder, major depressive disorder, delirium, or bipolar disorder

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
Active Comparator: 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	Drug: Aripiprazole tablet, 10 mg; Aripiprazole tablet 10 mg po qd x 42 days; Other Names: OPC-14597
Active Comparator: 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	Drug: Aripiprazole tablet, 30 mg; Aripiprazole tablet 30 mg po qd x 42 days; Other Names: OPC-14597
Placebo Comparator: Placebo Group; Participants were given a single pill administered once daily	Drug: Placebo tablet; Placebo tablet po qd x 42 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and Day 42
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.	Baseline and Day 42
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).	Baseline and Day 42
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).	Baseline and Day 42
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).	Baseline and Day 42

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline and Day 42
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.	Baseline and Day 42

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Investigators: Study Director: Margaretta Nyilas, M.D., Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Correll CU, Zhao J, Carson W, Marcus R, McQuade R, Forbes RA, Mankoski R. Early antipsychotic response to aripiprazole in adolescents with schizophrenia: predictive value for clinical outcomes. J Am Acad Child Adolesc Psychiatry. 2013 Jul;52(7):689-698.e3. doi: 10.1016/j.jaac.2013.04.018. Epub 2013 Jun 5.
• Robb AS, Carson WH, Nyilas M, Ali M, Forbes RA, Iwamoto T, Assuncao-Talbott S, Whitehead R, Pikalov A. Changes in positive and negative syndrome scale-derived hostility factor in adolescents with schizophrenia treated with aripiprazole: post hoc analysis of randomized clinical trial data. J Child Adolesc Psychopharmacol. 2010 Feb;20(1):33-8. doi: 10.1089/cap.2008.0163.
• Findling RL, Robb A, Nyilas M, Forbes RA, Jin N, Ivanova S, Marcus R, McQuade RD, Iwamoto T, Carson WH. A multiple-center, randomized, double-blind, placebo-controlled study of oral aripiprazole for treatment of adolescents with schizophrenia. Am J Psychiatry. 2008 Nov;165(11):1432-41. doi: 10.1176/appi.ajp.2008.07061035. Epub 2008 Sep 2.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: January 19, 2005
• First Submitted That Met QC Criteria: January 19, 2005
• First Posted (Estimate): January 20, 2005

Study Record Updates

• Last Update Posted (Estimate): August 10, 2012
• Last Update Submitted That Met QC Criteria: August 6, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Schizophrenia; Aripiprazole
• 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: 31-03-239