Clinical trial NCT01907360: Pharmacokinetics of HLD200 in Children and Adolescents With ADHD
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Attention-Deficit Hyperactivity Disorder
Lead sponsor: Ironshore Pharmaceuticals and Development, Inc
Sponsor class: OTHER
First posted: 2013-07-24
Enrollment: 29
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open-label, single-treatment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: PK Parameters for Rate and Extent of Absorption of MPH: Lag Time
timeFrame: 48hrs
measure: PK Parameters for Rate and Extent of Absorption of MPH: Cmax
timeFrame: 48hrs
measure: PK Parameters for Rate and Extent of Absorption of MPH: Tmax
timeFrame: 48hrs
measure: PK Parameters for Rate and Extent of Absorption of MPH: AUC0-tz
timeFrame: 48hrs
measure: PK Parameters for Rate and Extent of Absorption of MPH: AUC0-inf
timeFrame: 48hrs
Secondary outcomes:
Other outcomes:
measure: PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve
timeFrame: 48hrs
Locations:
city: Las Vegas
country: United States
facility: Centre for Psychiatry & Behavioral Medicine, Inc.
state: Nevada
Study officials:
affiliation: Centre for Psychiatry & Behavioral Medicine, Inc.
name: Ann Childress, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Childress A, Mehrotra S, Gobburu J, McLean A, DeSousa NJ, Incledon B. Single-Dose Pharmacokinetics of HLD200, a Delayed-Release and Extended-Release Methylphenidate Formulation, in Healthy Adults and in Adolescents and Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2018 Feb;28(1):10-18. doi: 10.1089/cap.2017.0044. Epub 2017 Oct 17.