PK/PD Pediatric ADHD Classroom Study

NCT02536105 | Completed Results DMC

• 2 other identifiers: 2015P0011135U01FD005240
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the association between blood drug levels and the corresponding scores of commonly used behavioral instruments based upon data collected following administration of three different methylphenidate hydrochloride extended-release drug products in children with ADHD.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

Attention Deficit Hyperactivity Disorder; ADHD

Outcome Measures

Primary Outcomes (4)

• Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products

  The Permanent Product Measure of Performance (PERMP) involves objective individualized mathematics tests. Scores will be obtained ten times on each classroom day at pre-dose, and at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose. PERMP Attempted is reported here. Scale ranges 0 math questions answered to 400 math questions answered. The more number of questions answered (better score), the higher the PERMP Attempted score is.

  0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day

• Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products

  The Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scale is a validated, 13-item rating of subjective impairment of classroom behaviors (0 = normal/no impairment; 1 = slight impairment; 2 = mild impairment; 3 = moderate impairment; 4 = severe impairment; 5 = very severe impairment; 6 = maximal impairment). The SKAMP consists of four subscales: SKAMP-Attention, SKAMP-Deportment, SKAMP-Quality of Work, and SKAMP-Compliance, in addition to SKAMP-Total (reported here). SKAMP-Total is a sum of the four sub-scales and has a range of 0-78. The higher the score, the higher the impairment. Scores will be obtained during each classroom cycle during each full laboratory classroom day at pre-dose, and at 0.5, 1.5, 2.5, 4, 5, 6, 8, 10, and 12 hours post-dose. The scores will be based on the child's behavior during 20 minutes of each cycle.

  0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day

• Maximum Drug Concentration Observed (Cmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products

  PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Cmax will be measured. The objectives of this measure is to estimate PK metrics, including Cmax, appropriate for characterizing rate and extent of absorption in each phase of the drug release and the evaluate the disposition and eliminating processes for each medication studied. The minimum value is pg/mL and there is was no maximum defined prior to the interventions.

  0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day

• Time to Reach Cmax (Tmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products

  PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Tmax will be measured

  0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day

Study Arms (4)

Methylphenidate HCl ER tablets 1

ACTIVE COMPARATOR

During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase

Drug: Methylphenidate HCl ER tablets 1

Placebo

PLACEBO COMPARATOR

During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators.

Drug: Placebo

Methylphenidate HCl ER tablets 2

ACTIVE COMPARATOR

During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase

Drug: Methylphenidate HCl ER tablets 2

Methylphenidate HCl ER for suspension

ACTIVE COMPARATOR

During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase

Drug: Methylphenidate HCl ER for suspension

Interventions

Methylphenidate HCl ER tablets 1 DRUG

Methylphenidate HCl ER tablets 1

Placebo DRUG

Placebo

Methylphenidate HCl ER tablets 2 DRUG

Methylphenidate HCl ER tablets 2

Methylphenidate HCl ER for suspension DRUG

Methylphenidate HCl ER for suspension

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and female outpatients
• Ages 6-12 years at time of screening
• Judged by the investigator to be physically healthy and suitable for participation in the study
• Diagnosis of DSM-5ADHD combined, predominantly inattentive or hyperactive/impulsive presentation, per clinical evaluation and confirmed by the MINI-KID
• Clinical Global Impressions-Severity (CGI-S) ≥ 3
• ≥ 90th percentile normative value for gender and age on the ADHD RS-IV total score at screening or baseline
• Study participant has a parent/legal guardian who is willing and able to give written informed consent for him/her to participate in the study
• Study participant must be able to give assent to participate in the trial
• Study participant and legal guardian must be able to speak and understand English
• Able to tolerate multiple finger pricks
• Willing to comply with all study procedures

You may not qualify if:

• Current (last month) psychiatric diagnosis other than specific phobia, motor skills disorders, oppositional defiant disorder, sleep disorders, elimination disorders, adjustment disorders, learning disorders, or communication disorders. Participants with school phobia or separation anxiety will not be eligible
• Cognitively impaired, in the investigator's opinion
• Any clinically significant chronic medical condition that, in the judgment of the investigator, may interfere with the participant's ability to participate in the study
• Seizure disorder excluding a history of febrile seizures
• Thyroid disease
• Tourette's disorder or chronic tic disorder (mild medication induced tics are allowed)
• Serious cardiac condition including cardiomyopathy, serious arrhythmias, structural cardiac disorders, or severe hypertension
• Glaucoma
• Current or recent (within the past 6 months) DSM-5 drug dependence or substance abuse (excluding nicotine and caffeine)
• Pregnant or nursing females. Females must have a negative urine pregnancy test at screening as well as four additional visits and must be abstinent or use adequate and reliable contraception throughout the study
• Currently treated and satisfied with ADHD medication
• Current psychotropic medications other than sedative hypnotics for sleep
• Use of atomoxetine, clonidine, guanfacine or a monoamine oxidase inhibitor within 28 days of the baseline visit
• Participation in another investigational medication study within 30 days prior to screening
• Clinically significant abnormal laboratory result, electrocardiogram (ECG) result, physical examination, or vital signs at screening that the investigator considers to be inappropriate to allow participation in the study

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Food and Drug Administration (FDA): collaborator
• Center for Psychiatry And Behavioral Medicine Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Center for Psychiatry and Behavioral Medicine

Las Vegas, Nevada, 89128, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Suspensions

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Thomas Spencer
• Organization: Massachusetts General Hospital

spencer@helix.mgh.harvard.edu

617-724-5600

Study Officials

• Thomas Spencer, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief, Clinical and Research Program, Pediatric Psychopharmacology

Study Record Dates

• First Submitted: August 24, 2015
• First Posted: August 31, 2015
• Study Start: May 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: December 10, 2019
• Results First Posted: December 10, 2019

Record last verified: 2019-11

Locations

US (2)