Pharmacokinetics of HLD200 in Children and Adolescents With ADHD

Study Overview
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Brief Summary
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This study was designed to assess the pharmacokinetic effects of a single dose of HLD200 (methylphenidate hydrochloride) in children and adolescents with ADHD.

Detailed Description
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This study utilized a single-center, open-label, single-treatment, fasted design to examine the rate and extent of absorption of evening-administered HLD200 in children (6-12 years) and adolescents (13-17 years) with ADHD. Following a screening period that included five days washout to allow for clearance of any prior ADHD medications, subjects were domiciled in-clinic and administered HLD200 (B-formulation; 54 mg; oral capsule) at 9 pm under fasted conditions. Subjects were then observed for safety and tolerability and a total of 18 blood samples collected during a 48 hour period (at t=0, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 36 and 48 hours post-dosing). These samples were then assayed for methylphenidate plasma concentrations and this data used for calculation of pharmacokinetic parameters.

Official Title
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A Phase I/II, Single Center, Single-Treatment, Open-Label, Adaptive Clinical Trial Design Examining the Pharmacokinetic Effects of up to Two Separate HLD200 Modified Release Formulations of Methylphenidate in Adolescent and Pediatric Subjects With ADHD

Conditions
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Attention-Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: HLD200 (methylphenidate hydrochloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adolescents (13-17 years) and children (6-12 years). Previous diagnosis of ADHD and confirmation using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). ADHD symptoms controlled on a stable dose of ADHD medication. Subjects should be on MPH or have previous history of symptom control during treatment with MPH. Physical examination free of clinically significant findings, unless deemed NCS by the Investigator and Medical Monitor; Able to swallow treatment capsules; Available for entire study period; Provision of informed consent (from the parent[s] and/or legal representative[s]) and assent (from the subject); and Female subjects of childbearing potential (i.e., post-menarche) required to have a negative result on urine pregnancy testing (and will be given specific instructions on avoiding pregnancy during trial) Exclusion Criteria: Any known history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, ophthalmologic disease, unless deemed NCS by the Investigator and the Medical Monitor; Presence of any significant physical or organ abnormality; Any illness during the 4 weeks before this study, unless deemed NCS by the Investigator and the Clinical and/or Medical Monitor; Severe comorbid psychiatric diagnosis that may affect subject safety or confound results (e.g., psychosis, bipolar disorder); Known history of moderate to severe asthma; Known history of severe allergic reaction (including drugs, food, insect bites, environmental allergens); Known history of seizures (except febrile seizures prior to age 5), anorexia nervosa, bulimia or current diagnosis or family history of Tourette's disorder; Subject who are severely underweight or overweight. Clinical value outside of the acceptable ranges, unless deemed NCS significant per the Investigator; Positive history for hepatitis B, hepatitis C and Human Immunodeficiency Virus (HIV); Positive screening for illicit drug use, and/or current health conditions or use of medications that might confound the results of the study or increase risk to the subject; Use of prescription medications (except ADHD medications) within 7 days and over-the counter medications (except birth control) within the 3 days preceding study enrollment, unless deemed acceptable by the Investigator and Clinical and/or Medical Monitor; Blood draws of 50 ml to 249 ml within the 30 days, 250 ml to 449 ml within the 45 days and ≥ 450 ml within the 60 days preceding study enrollment; Participation in clinical trial with an investigational drug within the 30 days preceding study enrollment; Intolerance to venipuncture; and Current suicidal ideation or history of suicidality determined as a significant finding on the Columbia-Suicide Severity Rating Scale (C-SSRS) by the investigator (Baseline C-SSRS for adolescents; Pediatric Baseline C-SSRS for children).

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: Sequential Assignment
Interventional Model Description: Open-label, single-treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLD200 (methylphenidate hydrochloride) in Adolescents<br>HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 13-17 years. | Drug: HLD200 (methylphenidate hydrochloride)<br> <br> * Other names: JORNAY PM;|
| Experimental: HLD200 (methylphenidate hydrochloride) in Children<br>HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 6-12 years. | Drug: HLD200 (methylphenidate hydrochloride)<br> <br> * Other names: JORNAY PM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameters for Rate and Extent of Absorption of MPH: Lag Time | The absorption lag time for methylphenidate in plasma expressed in hours is the difference in time between the drug administration and the last time point where the drug concentration was below the limit of assay quantitation. | 48hrs | 
| PK Parameters for Rate and Extent of Absorption of MPH: Cmax | The maximum drug concentration of methylphenidate in plasma. | 48hrs | 
| PK Parameters for Rate and Extent of Absorption of MPH: Tmax | The time to reach maximum concentration of methylphenidate in plasma. | 48hrs | 
| PK Parameters for Rate and Extent of Absorption of MPH: AUC0-tz | Area under the methylphenidate plasma concentration-time curve to time point tz (AUC0-tz), where tz was the last time point over the time interval with a measurable drug concentration | 48hrs | 
| PK Parameters for Rate and Extent of Absorption of MPH: AUC0-inf | The area under the methylphenidate plasma concentration-time curve to infinite time | 48hrs |