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

Phase 4

Completed

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

• Registration Number: NCT02470234
• Lead Sponsor: Rhodes Pharmaceuticals, L.P.

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®.

Study Timeline

• Study First Submitted: 2015-06-03
• Study First Submitted QC: 2015-06-11
• Study First Posted: 2015-06-12
• Study Start: 2016-07-30
• Primary Completion: 2017-07-20
• Study Completion: 2017-08-07
• Results First Submitted: 2020-09-21
• Status Verified: 2021-10
• Results First Submitted QC: 2021-10-27
• Last Update Submitted: 2021-10-27
• Results First Posted: 2021-11-24
• Last Update Posted: 2021-11-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methylphenidate HCl ER Capsules, 10 mg	Methylphenidate HCl ER Capsules, 10 mg	Methylphenidate Hydrochloride Extended Release Capsules, 10 mg. Active drug, administered once
Methylphenidate HCl ER Capsules, 20 mg	Methylphenidate HCl ER Capsules, 20 mg	Methylphenidate Hydrochloride Extended Release Capsules, 20 mg. Active drug, administered once
Methylphenidate HCl ER Capsules, 15 mg	Methylphenidate HCl ER Capsules, 15 mg	Methylphenidate Hydrochloride Extended Release Capsules, 15 mg. Active drug, administered once

Primary Outcome Measures

Name	Time	Method
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
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
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
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
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

Secondary Outcome Measures

Name	Time	Method
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
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

Trial Locations

Locations (2)

Qps-Mra, Llc; 🇺🇸 South Miami, Florida, United States

Duke Psychiatry and Behavioral Sciences, Duke University School of Medicine; 🇺🇸 Durham, North Carolina, United States