Aripiprazole Pharmacokinetics (PK) and Tolerability Study... | NCT00102479

NCT00102479

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
aripiprazole 20 mg	Experimental	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 25 mg	Experimental	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 30 mg	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Aripiprazole	Drug	Aripiprazole tablets ranging from 2 to 30 mg to be taken orally once a day.	aripiprazole 20 mg aripiprazole 25 mg aripiprazole 30 mg

Outcomes Module

Primary Outcomes

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.

Secondary Outcomes

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.

Eligibility Module

Eligibility Criteria

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.

PubMed Identifier	Type	Citation	Retractions
18626272	Derived	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.

Label	URL
Otsuka Clinical Trial Website	View source

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.
FG002	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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.
BG001

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

All enrolled participants who received study drug and who had a baseline and a post-baseline score for CGI-Severity or a post-baseline score for CGI Improvement were included in the efficacy analysis.

Posted

Number

Percentage of Participants

14 Days

ID	Title	Description
OG000	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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 mg. Following the dose-escalation phase, participants entered the fixed-dose phase and received 20 mg for 14 days.

ID	Term
D012559	Schizophrenia
D000087122	Mania

ID	Term
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001523	Mental Disorders
D019954	Neurobehavioral Manifestations
D009461	Neurologic Manifestations

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D015363	Quinolones