Pharmacokinetic Study in Children and Adolescents Aged 6 to 17 Years Who Have Been Diagnosed With ADHD

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Attention Deficit Hyperactivity Disorder (ADHD)

Intervention / Treatment
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* Drug: SHP465 12.5mg
* Drug: SHP465 25mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP465 12.5 mg<br>A single dose of SHP465 12.5 mg for Subjects aged 6-12 years | Drug: SHP465 12.5mg<br> <br> |
| Experimental: SHP465 25 mg<br>A single dose of SHP465 25 mg for Subjects aged 13-17 years | Drug: SHP465 25mg<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Drug Concentration (Cmax) of Dextroamphetamine (d-amphetamine) in Plasma | Maximum concentration occurring at time of maximum observed concentration of d-amphetamine during a dosing interval. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Maximum Observed Drug Concentration (Cmax) for Levoamphetamine (l-amphetamine) in Plasma | Maximum observed concentration of l-amphetamine during a dosing interval. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Time to Reach Maximum Observed Drug Concentration (Tmax) of Dextroamphetamine (d-amphetamine) in Plasma | Time to reach maximum observed drug concentration of d-amphetamine during a dosing interval. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Time to Reach Maximum Observed Drug Concentration (Tmax) of Levoamphetamine (l-amphetamine) in Plasma | Time to reach maximum observed drug concentration of l-amphetamine during a dosing interval. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Area Under the Curve From Zero to Infinity (AUC0-infinity) of Dextroamphetamine (d-amphetamine) in Plasma | AUC0-infinity was calculated using the observed value of the last non-zero concentration of d-amphetamine in plasma. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Area Under the Curve From Zero to Infinity (AUC0-infinity) of Levoamphetamine (l-amphetamine) in Plasma | AUC0-infinity was calculated using the observed value of the last non-zero concentration of l-amphetamine in plasma. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Area Under the Curve From Zero to Last Measurable Concentration (AUClast) of Dextroamphetamine (d-amphetamine) in Plasma | Area under the curve from the time of dosing to the last measurable concentration of d-amphetamine in plasma. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Area Under the Curve From Zero to Last Measurable Concentration (AUClast) of Levoamphetamine (l-amphetamine) in Plasma | Area under the curve from the time of dosing to the last measurable concentration of l-amphetamine in plasma. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Terminal Half-life (t½) of Dextramphetamine (d-amphetamine) in Plasma | Terminal half-life is the time measured for the plasma concentration of d-amphetamine to decrease by one half. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Terminal Half-life (t½) of Levoamphetamine (l-amphetamine) in Plasma | Terminal half-life is the time measured for the plasma concentration of l-amphetamine to decrease by one half. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Total Body Clearance for Extravascular Administration (CL/F) of Dextroamphetamine (d-amphetamine) | Total body clearance for extravascular administration of d-amphetamine divided by the fraction of dose absorbed. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Total Body Clearance for Extravascular Administration (CL/F) of Levoamphetamine (l-amphetamine) | Total body clearance for extravascular administration of l-amphetamine divided by the fraction of dose absorbed. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Volume of Distribution After Extravascular Administration (Vz/F) of Dextroamphetamine (d-amphetamine) | Volume of distribution for d-amphetamine based on the terminal phase following extravascular administration divided by the fraction of dose absorbed. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 
| Volume of Distribution After Extravascular Administration (Vz/F) of Levoamphetamine (l-amphetamine) | Volume of distribution for l-amphetamine based on the terminal phase following extravascular administration divided by the fraction of dose absorbed. | Pre-dose, 2, 4, 6, 8, 10, 12, 24, 48, 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE was considered as treatment-emergent (TEAE) if it had a start date and time on or after the dose of investigational product and no later than 72 hours after dosing, or if it had a start date and time before the date and time of the dose of investigational product, but increased in severity on or after the date and time of the dose of investigational product and no later than 72 hours after dosing. | From start of study drug administration up to follow-up (up to 9 days) | 
| Number of Participants With TEAE Related to Vital signs, Electrocardiogram (ECG), and Clinical Laboratory Tests | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Vital signs included blood pressure, pulse rate, respiratory rate, and body temperature. ECG was analysed as 12-lead ECG. Clinical laboratory test is considered for biochemistry, Hematology and Urinalysis. | From start of study drug administration up to follow-up (up to 9 days) | 
| Number of Participants With Suicidal Behavior and / or Ideation (Yes Response) on the Columbia Suicide Severity Rating Scale (C-SSRS) | C-SSRS is a clinician rated assessment of suicidal behavior and / or intent categorized as: Suicidal behavior=a yes response to any of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide); Suicidal ideation=a yes response to any one of 5 suicidal ideation questions which includes wish to be dead, and 4 different categories of active suicidal ideation (thought, thought with method, thought with intent, thought with plan and intent). | Baseline up to Day 4 |