Pharmacokinetic Study of Methylphenidate HCl Extended-Release Capsules in Children 4 to Under 6 Years of Age With ADHD (PK003)

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

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.

Study Overview

• Status: Completed
• Conditions: Attention-Deficit/Hyperactivity Disorder
• Intervention / Treatment: Drug: Methylphenidate HCl ER Capsules, 10 mg; Drug: Methylphenidate HCl ER Capsules, 15 mg; Drug: Methylphenidate HCl ER Capsules, 20 mg

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®.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Psychiatry and Behavioral Sciences, Duke University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methylphenidate HCl ER Capsules, 10 mg; Methylphenidate Hydrochloride Extended Release Capsules, 10 mg. Active drug, administered once	Drug: Methylphenidate HCl ER Capsules, 10 mg; Methylphenidate Hydrochloride Extended-Release Capsules, 10 mg administered once daily in the morning; Other Names: Aptensio XR®, 10 mg
Experimental: Methylphenidate HCl ER Capsules, 15 mg; Methylphenidate Hydrochloride Extended Release Capsules, 15 mg. Active drug, administered once	Drug: Methylphenidate HCl ER Capsules, 15 mg; Methylphenidate Hydrochloride Extended-Release Capsules, 15 mg administered once daily in the morning; Other Names: Aptensio XR®, 15 mg
Experimental: Methylphenidate HCl ER Capsules, 20 mg; Methylphenidate Hydrochloride Extended Release Capsules, 20 mg. Active drug, administered once	Drug: Methylphenidate HCl ER Capsules, 20 mg; Methylphenidate Hydrochloride Extended-Release Capsules, 20 mg administered once daily in the morning; Other Names: Aptensio XR®, 20 mg

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rhodes Pharmaceuticals, L.P.
• Investigators: Study Director: Akwete Adjei, Ph.D., Rhodes Pharmaceuticals, L.P.

Publications and helpful links

General Publications

• Adjei AL, Chaudhary I, Kollins SH, Padilla A. A Pharmacokinetic Study of Methylphenidate Hydrochloride Multilayer Extended-Release Capsules (Aptensio XR(R)) in Preschool-Aged Children with Attention-Deficit/Hyperactivity Disorder. Paediatr Drugs. 2020 Oct;22(5):561-570. doi: 10.1007/s40272-020-00409-z.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2016
• Primary Completion (Actual): July 20, 2017
• Study Completion (Actual): August 7, 2017

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: June 11, 2015
• First Posted (Estimate): June 12, 2015

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Children; ADHD; Pharmacokinetics
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: RP-BP-PK003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No