Pharmacokinetics of HLD200 in Children and Adolescents With ADHD

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

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

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.

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).