Pharmacokinetic Study of Methylphenidate HCl Extended-Release Capsules in Children 4 to Under 6 Years of Age With ADHD

Study Overview
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Brief Summary
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To assess the pharmacokinetics of a single dose of Aptensio XR® (methylphenidate hydrochloride extended-release) capsules under fed conditions in male or female children 4 to under 6 years of age with ADHD.

Detailed Description
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This will be a multi-center, open-label, single-dose, study to assess the pharmacokinetics of Aptensio XR® (methylphenidate hydrochloride extended-release) capsules in male and female children 4 to under 6 years of age with ADHD in fed condition. Screening Procedures: After obtaining written informed consent from parents, subjects will undergo a complete medical and medication history, demographic data (including sex, age, race, ethnicity, body weight (kg), height (cm), Body Mass Index (BMI) (kg/m2), physical examination, vital signs evaluation (sitting blood pressure, pulse rate, respiration rate, temperature and pulse oximetry), resting 12-lead electrocardiogram (ECG), clinical laboratory tests and concomitant medication within 28 days prior to receiving study drug. On Day 1: subjects will receive a single oral dose of Aptensio XR®.

Official Title
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A Pharmacokinetic Study of Aptensio XR® (Methylphenidate Hydrochloride (HCl) Extended-release) Capsules in Male or Female Pre-School Children 4 to Under 6 Years of Age With Attention Deficit Hyperactivity Disorder (ADHD) in Fed Condition

Conditions
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Attention-Deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: Methylphenidate HCl ER Capsules, 10 mg
* Drug: Methylphenidate HCl ER Capsules, 15 mg
* Drug: Methylphenidate HCl ER Capsules, 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is a male or female between the ages of 4 and under 6 years old. Patient has a history consistent with ADHD, meets the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for ADHD, inattentive, hyperactivity or combined. Patient must meet criteria for ADHD diagnosis on Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime (KSADS-PL) and clinical interview by experienced clinician; symptoms must have been present for at least 6 months. Subject has had prior behavioral treatment or subject's symptoms are severe enough to warrant treatment without prior behavioral treatment, and patient is on a stable dose of either immediate-release or extended-release methylphenidate. Subject must have age- and sex-adjusted ratings of ≥ 90th percentile Total Score on the Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Preschool Version, a Clinical Global Impressions -Severity Score of ≥4 and a Child Global Assessment Scale rating of <65 after methylphenidate washout and prior to obtaining pharmacokinetic samples. Ratings may be completed via telephone on day-1. Parents or guardians of patients must have the ability to read and understand the language in which the Informed Consent is written and are mentally and physically competent to provide written informed consents for their child. Patient and/or parent are/is able to understand English in order to provide assent and is otherwise able to comply with the study protocol. Exclusion Criteria: Patient has allergy to methylphenidate or amphetamines, or history of serious adverse reaction to methylphenidate. Patient has a history of tension, agitation, glaucoma, thyrotoxicosis, tachyarrhythmias or severe angina pectoris or patient with serious or unstable medical illness such as asthma, diabetes or seizures. A history of motor or vocal tics or Tourette's syndrome Patient is receiving monoamine oxidase inhibitors, anticonvulsants (phenobarbital, phenytoin, primidone), coumarin anticoagulants, presser agents, guanethidine, tricyclic antidepressants (imipramine, desipramine, selective serotonin inhibitors (SSRIs), or herbal remedies (e.g., melatonin). Patient has serious hypertension. Patient has a history of disorders of the sensory organs, particularly deafness, severe or profound retardation. Patient has any other unstable psychiatric condition requiring treatment. Patient is at risk for substance abuse. Evidence of current physical, sexual, or emotional abuse Living with anyone who currently abuses stimulants or cocaine History of bipolar disorder in both biological parents

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 5 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, single-dose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate HCl ER Capsules, 10 mg<br>Methylphenidate Hydrochloride Extended Release Capsules, 10 mg. Active drug, administered once | Drug: Methylphenidate HCl ER Capsules, 10 mg<br>* Methylphenidate Hydrochloride Extended-Release Capsules, 10 mg administered once daily in the morning<br>* Other names: Aptensio XR®, 10 mg;|
| Experimental: Methylphenidate HCl ER Capsules, 15 mg<br>Methylphenidate Hydrochloride Extended Release Capsules, 15 mg. Active drug, administered once | Drug: Methylphenidate HCl ER Capsules, 15 mg<br>* Methylphenidate Hydrochloride Extended-Release Capsules, 15 mg administered once daily in the morning<br>* Other names: Aptensio XR®, 15 mg;|
| Experimental: Methylphenidate HCl ER Capsules, 20 mg<br>Methylphenidate Hydrochloride Extended Release Capsules, 20 mg. Active drug, administered once | Drug: Methylphenidate HCl ER Capsules, 20 mg<br>* Methylphenidate Hydrochloride Extended-Release Capsules, 20 mg administered once daily in the morning<br>* Other names: Aptensio XR®, 20 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum plasma concentration | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| AUC(0-t) | Area under the plasma concentration versus time curve (calculated to the last measurable observation). AUC: Area Under the Curve | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| AUC(0-inf) | Area under the plasma concentration versus time curve, extrapolated to infinity. AUC: Area Under the Curve | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| AUC/D | Dose-normalized AUC0-t. AUC: Area Under the Curve | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| CL/F | Apparent clearance. CL: Clearance | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| V(Dss)/F | Volume of distribution | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| Cmax/Dose | Dose-normalized Cmax | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax | Time to peak plasma concentration | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| T1/2 | Elimination half-life | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 
| Kel | Terminal elimination constant | Day 1 at time 0 (within 30-60 minutes pre-dose) and 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Children, Pharmacokinetics