A Phase 1, Open-label Study of the Pharmacokinetics of d- and L-amphetamine After a Single Dose of SHP465 12.5 mg or 25 mg Administered to Children and Adolescents Aged 6 to17 Years With Attention-Deficit Hyperactivity Disorder (ADHD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 27
- 试验地点
- 3
- 主要终点
- Time to Reach Maximum Observed Drug Concentration (Tmax) of Dextroamphetamine (d-amphetamine) in Plasma
研究概览
简要总结
To provide additional, required information on the pharmacokinetic profile of SHP465 in the targeted population (children and adolescents aged 6-17 years of age with ADHD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6 to 17 years inclusive at the time of consent/assent. The date of signature of the informed consent/assent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the first screening visit.
- •Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
- •Subject meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for a primary diagnosis of ADHD based on an accepted ADHD diagnostic instrument and documented in the subject's medical record. Subject's ADHD is currently adequately controlled with an amphetamine-based product.
- •Subject is functioning at an age appropriate level intellectually, as determined by the investigator.
- •Must be considered "healthy". Healthy status is defined by absence of evidence of any active or chronic disease other than their ADHD following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
- •Ability to swallow a capsule of investigational product whole.
排除标准
- •Current use of any ADHD medication other than an amphetamine-based product.
- •History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease other than their ADHD
- •Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment
- •Subject has a current, controlled or uncontrolled, comorbid psychiatric diagnosis with significant symptoms
- •Subject meets DSM-V diagnosis of conduct disorder.
- •Subject is considered a suicide risk in the opinion of the investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation.
- •Subject is underweight based on Centers for Disease Control and Prevention (CDC) body mass index (BMI)- for-age sex-specific values
- •Subject is significantly overweight based on CDC BMI-for-age sex specific values
- •Subject has a known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems
- •Subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments conducted in the study
- •Subject has a history of seizure, a chronic or current tic disorder, or a current diagnosis of Tourette's Disorder. Subject has a history of tics that are judged to be exclusionary.
- •Subject's blood pressure measurements exceed the 90th percentile for age, sex, and height
- •Subject has a known history of hypertension.
- •Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
- •Subject has any clinically significant ECG or clinically significant laboratory abnormality
- •Subject has abnormal thyroid function
- •Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any ingredients.
- •History of alcohol or other substance abuse within the last year. Subjects with a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence will be excluded.
- •Use Within 30 days prior to the first dose of investigational product:
- •have used an investigational product
- •have been enrolled in a clinical study (including vaccine)
- •have had any substantial changes in eating habits
- •A positive screen for alcohol or drugs of abuse. A positive hepatitis B surface antigen (HBsAg); hepatitis C virus (HCV); or HIV antibody screen.
- •Use of tobacco in any form in the last 30 days
- •Prior screen failure, enrollment, or participation in this study.
研究组 & 干预措施
SHP465 12.5 mg
A single dose of SHP465 12.5 mg for Subjects aged 6-12 years
干预措施: SHP465 12.5mg (Drug)
SHP465 25 mg
A single dose of SHP465 25 mg for Subjects aged 13-17 years
干预措施: SHP465 25mg (Drug)
结局指标
主要结局
Time to Reach Maximum Observed Drug Concentration (Tmax) of Dextroamphetamine (d-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Time to reach maximum observed drug concentration of d-amphetamine during a dosing interval.
Area Under the Curve From Zero to Infinity (AUC0-infinity) of Levoamphetamine (l-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
AUC0-infinity was calculated using the observed value of the last non-zero concentration of l-amphetamine in plasma.
Volume of Distribution After Extravascular Administration (Vz/F) of Dextroamphetamine (d-amphetamine)
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Volume of distribution for d-amphetamine based on the terminal phase following extravascular administration divided by the fraction of dose absorbed.
Maximum Observed Drug Concentration (Cmax) for Levoamphetamine (l-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Maximum observed concentration of l-amphetamine during a dosing interval.
Area Under the Curve From Zero to Infinity (AUC0-infinity) of Dextroamphetamine (d-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
AUC0-infinity was calculated using the observed value of the last non-zero concentration of d-amphetamine in plasma.
Area Under the Curve From Zero to Last Measurable Concentration (AUClast) of Levoamphetamine (l-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Area under the curve from the time of dosing to the last measurable concentration of l-amphetamine in plasma.
Terminal Half-life (t½) of Levoamphetamine (l-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Terminal half-life is the time measured for the plasma concentration of l-amphetamine to decrease by one half.
Total Body Clearance for Extravascular Administration (CL/F) of Levoamphetamine (l-amphetamine)
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Total body clearance for extravascular administration of l-amphetamine divided by the fraction of dose absorbed.
Maximum Observed Drug Concentration (Cmax) of Dextroamphetamine (d-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Maximum concentration occurring at time of maximum observed concentration of d-amphetamine during a dosing interval.
Terminal Half-life (t½) of Dextramphetamine (d-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Terminal half-life is the time measured for the plasma concentration of d-amphetamine to decrease by one half.
Area Under the Curve From Zero to Last Measurable Concentration (AUClast) of Dextroamphetamine (d-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Area under the curve from the time of dosing to the last measurable concentration of d-amphetamine in plasma.
Volume of Distribution After Extravascular Administration (Vz/F) of Levoamphetamine (l-amphetamine)
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Volume of distribution for l-amphetamine based on the terminal phase following extravascular administration divided by the fraction of dose absorbed.
Time to Reach Maximum Observed Drug Concentration (Tmax) of Levoamphetamine (l-amphetamine) in Plasma
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Time to reach maximum observed drug concentration of l-amphetamine during a dosing interval.
Total Body Clearance for Extravascular Administration (CL/F) of Dextroamphetamine (d-amphetamine)
时间窗: Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose
Total body clearance for extravascular administration of d-amphetamine divided by the fraction of dose absorbed.
次要结局
- Number of Participants With Suicidal Behavior and / or Ideation ("Yes" Response) on the Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline up to Day 4)
- Number of Participants With TEAE Related to Vital signs, Electrocardiogram (ECG), and Clinical Laboratory Tests(From start of study drug administration up to follow-up (up to 9 days))
- Participants with Treatment-emergent Adverse Events (TEAEs)(From start of study drug administration up to follow-up (up to 9 days))