Aripiprazole Pharmacokinetics (PK) and Tolerability Study in Children and Adolescents

A Phase II Study to Test PK Tolerability in Children and Adolescents

The purpose of this trial is to assess the safety, tolerability and pharmacokinetics of aripiprazole tablets following oral administration to children and adolescents.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Mania
• Intervention / Treatment: Drug: Aripiprazole

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female children and adolescents between 10 and 17 years, inclusive, preferentially with a primary schizophrenia spectrum diagnosis or bipolar spectrum disorder.
• Good physical health as determined by no clinically significant deviation from normal in medical history, clinical laboratory determination, electrocardiograms (ECG) and physical examinations conducted within 14 days prior to study enrollment.
• Both the legal guardian and study subject must have signed written informed consent. Consent must have been obtained prior to any screening evaluations.
• Subjects must have had a caretaker or guardian who could adequately complete appropriate documentation required by the protocol.

Exclusion Criteria:

• Sexually active males and females who were not practicing double-barrier birth control, or who were not remaining abstinent, during the study and for 30 days (females only) or 90 days (males only) following the last dose of study medication.
• All sexually active females of childbearing potential must have had a negative serum pregnancy test with results available prior to receiving study drug.
• Breastfeeding females were excluded.
• History of recent (within 6 months) drug or alcohol abuse as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Diagnostic Criteria for Drug and Alcohol Abuse and/or a positive urine screen for drugs of abuse.
• History of mental retardation or mental retardation assessed by the investigator.
• Subjects who were known to consume alcohol-containing beverages routinely.
• Subjects who consumed any alcohol-containing beverages during the screening period.
• Any neurological disorder with the exception of pervasive development disorder, attention deficit hyperactivity disorder, and Tourette's syndrome.
• Use of any antipsychotic medication, other prohibited psychotropic medication, and any cytochrome P450 2D6 (CYP2D6) and cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 inducers within 14 days prior to dosing and for the duration of the study.
• Use of any prescription medication not specifically approved by the medical monitor or study director.
• A positive hepatitis C antibody test.
• Females who were pregnant or lactating.
• Subjects who had participated in any clinical trial within 1 month prior to enrollment, or in a clinical trial involving psychotropic medication within 6 months prior to the end of baseline, unless permission was obtained from the sponsor.
• Donation of blood or plasma to a blood bank, or participation in a clinical study (except a screening visit) within 30 days prior to enrollment.
• Any major surgery within 30 days prior to enrollment.
• Blood transfusion within 30 days prior to enrollment.
• Inability to tolerate oral medication or swallow tablets.
• Evidence of organ dysfunction or any clinically significant deviation from normal in the physical, ECG, or clinical laboratory examinations.
• Subjects who, based upon clinical interview, presented a significant risk of suicidality or homicidality.
• Any other sound medical reason as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aripiprazole 20 mg; Participants were administered aripiprazole tablets to be taken orally once daily starting at a dose of 2 mg increased over 12 days to achieve a dose level of 20 milligrams (mg). Following the dose-escalation phase, participants entered the fixed-dose phase and received 20 mg for 14 days.	Drug: Aripiprazole; Aripiprazole tablets ranging from 2 to 30 mg to be taken orally once a day.; Other Names: Abilify®
Experimental: aripiprazole 25 mg; Participants were administered aripiprazole tablets to be taken orally once daily starting at a dose of 2 mg increased over 12 days to achieve a dose level of 25 milligrams (mg). Following the dose-escalation phase, participants entered the fixed-dose phase and received 25 mg for 14 days.	Drug: Aripiprazole; Aripiprazole tablets ranging from 2 to 30 mg to be taken orally once a day.; Other Names: Abilify®
Experimental: aripiprazole 30 mg; Participants were administered aripiprazole tablets to be taken orally once daily starting at a dose of 2 mg increased over 12 days to achieve a dose level of 30 mg. Following the dose-escalation phase, participants entered the fixed-dose phase and received 30 mg for 14 days.	Drug: Aripiprazole; Aripiprazole tablets ranging from 2 to 30 mg to be taken orally once a day.; Other Names: Abilify®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Able to Tolerate Maximum Dose Level	Dose toleration was defined as the following: during the course of the study the participant does not experience any untoward events or potentially clinically significant changes from baseline in laboratory values, vital signs, electrocardiogram (ECG) tracings, or Extrapyramidal symptoms (EPS) ratings (evaluation of parkinsonism, dyskinesia, and akathisia) that are assessed as possibly related to the drug, and would warrant adjustment or discontinuation of the study drug.	14 Days
Number of Participants With Adverse Events, Serious Adverse Events and Discontinuation Due to Adverse Event as a Measure of Safety	An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.	57 days
Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)	Blood samples were collected pre-dose and 1, 2, 3, 4, 6, 8, 10, and 24 hours post dose on Day 14 and were analyzed by a validated High-Performance Liquid Chromatography/ Mass Spectrometry (HPLC-MS/MS) method for aripiprazole. Css,max value was determined using observed data.	Pre-dose and 1 to 24 hours post-dose on Day 14
Aripiprazole Time to Maximum (Peak) Plasma Concentration (Tmax)	Blood samples were collected pre-dose and 1, 2, 3, 4, 6, 8, 10, 24 and 25 hours post dose on Day 14 and were analyzed by a validated High-Performance Liquid Chromatography/ Mass Spectrometry (HPLC-MS/MS) method for aripiprazole. Tmax value was determined using observed data.	Pre-dose and 1 to 25 hours post-dose on Day 14
Aripiprazole Area Under the Concentration-Time Curve at Steady-State (AUCτ)	Blood samples were collected pre-dose and 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose on Day 14 and were analyzed by a validated High-Performance Liquid Chromatography/ Mass Spectrometry (HPLC-MS/MS) method for aripiprazole. Values of AUCτ were estimated using the linear trapezoidal rule to the actual time of the 24-hour sample.	Pre-dose and 1 to 24 hours post-dose on Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Day 1 and Day 14	The severity of illness for each participant was rated using the CGI-S scale. The investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" using an 8-point scale where 0=not assessed, 1=normal, not at all ill; to 7=among the most extremely ill patients. A negative change from Baseline indicated improvement.	Baseline, Day 1, Day 14
Clinical Global Impression Scale-Improvement (CGI-I) Score at Day 1 and Day 14	The participant's overall improvement was rated for each participant using the CGI-I scale. The investigator rated the participant's total improvement by answering the following question: "Compared to his/her condition at baseline (prior to randomization), how much has the patient changed?" using an 8-point scale where 0=not assessed, 1=very much improved to 7=very much worse. Lower scores indicated improvement.	Days 1 and 14

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Findling RL, Kauffman RE, Sallee FR, Carson WH, Nyilas M, Mallikaarjun S, Shoaf SE, Forbes RA, Boulton DW, Pikalov A. Tolerability and pharmacokinetics of aripiprazole in children and adolescents with psychiatric disorders: an open-label, dose-escalation study. J Clin Psychopharmacol. 2008 Aug;28(4):441-6. doi: 10.1097/JCP.0b013e31817dd520.

Helpful Links

• Otsuka Clinical Trial Website
• Otsuka Clinical Trial Transparency

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2004
• Primary Completion (Actual): July 1, 2005
• Study Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: January 29, 2005
• First Submitted That Met QC Criteria: January 28, 2005
• First Posted (Estimated): January 31, 2005

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Aripiprazole; Pharmacokinetics,; acute mania in pediatric populations
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Mania; Schizophrenia; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinolones; Quinolines; Piperazines; Aripiprazole
• Other Study ID Numbers: 31-03-238

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No