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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01907360

Enrollment

Registered

2013-07-24

Start date

2013-08-31

Completion date

2013-10-31

Last updated

2021-12-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Attention-Deficit Hyperactivity Disorder

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.

Interventions

DRUGHLD200 (methylphenidate hydrochloride)

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Open-label, single-treatment

Eligibility

Sex/Gender

ALL

Age

6 Years to 17 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
PK Parameters for Rate and Extent of Absorption of MPH: Lag Time	48hrs	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.
PK Parameters for Rate and Extent of Absorption of MPH: Cmax	48hrs	The maximum drug concentration of methylphenidate in plasma.
PK Parameters for Rate and Extent of Absorption of MPH: Tmax	48hrs	The time to reach maximum concentration of methylphenidate in plasma.
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-tz	48hrs	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
PK Parameters for Rate and Extent of Absorption of MPH: AUC0-inf	48hrs	The area under the methylphenidate plasma concentration-time curve to infinite time

Other

Measure	Time frame	Description
PK Parameters for Rate and Extent of Absorption of MPH in Plasma: Plasma Concentration-time Curve	48hrs	To determine the rate and extent of absorption of methylphenidate following a single treatment of HLD200 (B formulation; 54 mg) in children and adolescents with ADHD, plasma samples were collected at t=0, 4, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 20, 22, 24, 36 and 48 hours post-HLD200 treatment and methylphenidate concentrations were determined.

Countries

United States

Participant flow

Pre-assignment details

A total of 29 subjects were enrolled (18 adolescents and 11 children in sequential cohorts). Following consent/assent and screening procedures, subjects were required to wash-out of all ADHD medications for 5 days prior clinic admission for testing.

Participants by arm

Arm	Count
HLD200 (Methylphenidate Hydrochloride) in Adolescents HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to adolescents aged 13-17 years.	18
HLD200 (Methylphenidate Hydrochloride) in Children HLD200 (B formulation, 54 mg, oral capsules) administered as a single treatment in the evening to children aged 6-12 years.	11
Total	29

Baseline characteristics

Characteristic	HLD200 (Methylphenidate Hydrochloride) in Adolescents	HLD200 (Methylphenidate Hydrochloride) in Children	Total
Age, Continuous	15.4 years STANDARD_DEVIATION 1.24	10.5 years STANDARD_DEVIATION 1.37	13.52 years STANDARD_DEVIATION 2.75
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	2 Participants	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants	9 Participants	24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Height (cm)	169.56 cm STANDARD_DEVIATION 6.487	143.18 cm STANDARD_DEVIATION 6.072	159.55 cm STANDARD_DEVIATION 14.434
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	1 Participants	3 Participants
Race (NIH/OMB) More than one race	2 Participants	2 Participants	4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) White	13 Participants	7 Participants	20 Participants
Sex: Female, Male Female	4 Participants	6 Participants	10 Participants
Sex: Female, Male Male	14 Participants	5 Participants	19 Participants
Weight (kg)	67.71 kg STANDARD_DEVIATION 14.588	36.08 kg STANDARD_DEVIATION 7.95	54.74 kg STANDARD_DEVIATION 19.704

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 18	0 / 11
other Total, other adverse events	10 / 18	6 / 11
serious Total, serious adverse events	0 / 18	0 / 11

Outcome results

Primary