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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02470234

Acronym

PK003

Enrollment

Registered

2015-06-12

Start date

2016-07-30

Completion date

2017-08-07

Last updated

2021-11-24

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

Conditions

Attention-Deficit/Hyperactivity Disorder

Keywords

ADHD, Children, Pharmacokinetics

Brief summary

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

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®.

Interventions

DRUGMethylphenidate HCl ER Capsules, 10 mg

Methylphenidate Hydrochloride Extended-Release Capsules, 10 mg administered once daily in the morning

DRUGMethylphenidate HCl ER Capsules, 15 mg

Methylphenidate Hydrochloride Extended-Release Capsules, 15 mg administered once daily in the morning

DRUGMethylphenidate HCl ER Capsules, 20 mg

Methylphenidate Hydrochloride Extended-Release Capsules, 20 mg administered once daily in the morning

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Intervention model description

Open-label, single-dose

Eligibility

Sex/Gender

ALL

Age

4 Years to 5 Years

Healthy volunteers

Inclusion criteria

1. Patient is a male or female between the ages of 4 and under 6 years old. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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

1. Patient has allergy to methylphenidate or amphetamines, or history of serious adverse reaction to methylphenidate. 2. 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. 3. A history of motor or vocal tics or Tourette's syndrome 4. 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). 5. Patient has serious hypertension. 6. Patient has a history of disorders of the sensory organs, particularly deafness, severe or profound retardation. 7. Patient has any other unstable psychiatric condition requiring treatment. 8. Patient is at risk for substance abuse. 9. Evidence of current physical, sexual, or emotional abuse 10. Living with anyone who currently abuses stimulants or cocaine 11. History of bipolar disorder in both biological parents

Design outcomes

Primary

Measure	Time frame	Description
Cmax/Dose	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	Dose-normalized Cmax
AUC/D	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	Dose-normalized AUC0-t. AUC: Area Under the Curve
CL/F	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	Apparent clearance. CL: Clearance
V(Dss)/F	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	Volume of distribution
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	Maximum plasma concentration
AUC(0-t)	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	Area under the plasma concentration versus time curve (calculated to the last measurable observation). AUC: Area Under the Curve
AUC(0-inf)	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	Area under the plasma concentration versus time curve, extrapolated to infinity. AUC: Area Under the Curve

Secondary

Measure	Time frame	Description
T1/2	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	Elimination half-life
Kel	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	Terminal elimination constant
Tmax	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	Time to peak plasma concentration

Countries

United States

Participant flow

Recruitment details

It was a parallel design study, where subjects were recruited from July 02, 2016 - July 19, 2017. Eligible subjects received one capsule of Methylphenidate HCl ER (10, 15, 20, 30, or 40 mg) on only one of the 3 dosing days depending on number of subjects recruited up each particular dosing day. Only 1 site was able to recruit subjects.

Participants by arm

Arm	Count
Methylphenidate HCl ER 10 mg Subjects received a single dose of Methylphenidate HCl ER 10 mg	5
Methylphenidate HCl ER 15 mg Subjects received a single dose of Methylphenidate HCl ER 15 mg	3
Methylphenidate HCl ER 20 mg Subjects received a single dose of Methylphenidate HCl ER 20 mg	2
Total	10

Baseline characteristics

Characteristic	Methylphenidate HCl ER 10 mg	Methylphenidate HCl ER 15 mg	Methylphenidate HCl ER 20 mg	Total
Age, Continuous	61.0 Months STANDARD_DEVIATION 8.03	63.3 Months STANDARD_DEVIATION 5.51	70.5 Months STANDARD_DEVIATION 0.71	63.6 Months STANDARD_DEVIATION 7.06
BMI	15.3 kg/m^2 STANDARD_DEVIATION 0.55	15.3 kg/m^2 STANDARD_DEVIATION 0.98	15.3 kg/m^2 STANDARD_DEVIATION 2.26	15.3 kg/m^2 STANDARD_DEVIATION 0.96
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	1 Participants	1 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	2 Participants	1 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	4 Participants	1 Participants	1 Participants	6 Participants
Race (NIH/OMB) More than one race	1 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	1 Participants	1 Participants	2 Participants
Sex: Female, Male Female	1 Participants	1 Participants	1 Participants	3 Participants
Sex: Female, Male Male	4 Participants	2 Participants	1 Participants	7 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 3	0 / 2
other Total, other adverse events	1 / 5	0 / 3	0 / 2
serious Total, serious adverse events	0 / 5	0 / 3	0 / 2

Outcome results

Primary

AUC(0-inf)

Area under the plasma concentration versus time curve, extrapolated to infinity. AUC: Area Under the Curve