A Phase II Study to Test PK Tolerability in Children and Adolescents
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 主要终点
- Percentage of Participants Able to Tolerate Maximum Dose Level
研究概览
简要总结
The purpose of this trial is to assess the safety, tolerability and pharmacokinetics of aripiprazole tablets following oral administration to children and adolescents.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Aripiprazole (Drug)
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.
干预措施: Aripiprazole (Drug)
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.
干预措施: Aripiprazole (Drug)
结局指标
主要结局
Percentage of Participants Able to Tolerate Maximum Dose Level
时间窗: 14 Days
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.
Number of Participants With Adverse Events, Serious Adverse Events and Discontinuation Due to Adverse Event as a Measure of Safety
时间窗: 57 days
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.
Aripiprazole Maximum Steady State Plasma Concentration (Css,Max)
时间窗: Pre-dose and 1 to 24 hours post-dose on Day 14
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.
Aripiprazole Time to Maximum (Peak) Plasma Concentration (Tmax)
时间窗: Pre-dose and 1 to 25 hours post-dose on Day 14
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.
Aripiprazole Area Under the Concentration-Time Curve at Steady-State (AUCτ)
时间窗: Pre-dose and 1 to 24 hours post-dose on Day 14
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.
次要结局
- Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) at Day 1 and Day 14(Baseline, Day 1, Day 14)
- Clinical Global Impression Scale-Improvement (CGI-I) Score at Day 1 and Day 14(Days 1 and 14)