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PK/PD Pediatric ADHD Classroom Study

Primary Purpose

Attention Deficit Hyperactivity Disorder

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Methylphenidate HCl ER tablets 1
Placebo
Methylphenidate HCl ER tablets 2
Methylphenidate HCl ER for suspension
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Attention Deficit Hyperactivity Disorder focused on measuring Attention Deficit Hyperactivity Disorder, ADHD

Eligibility Criteria

6 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male and female outpatients
  2. Ages 6-12 years at time of screening
  3. Judged by the investigator to be physically healthy and suitable for participation in the study
  4. Diagnosis of DSM-5ADHD combined, predominantly inattentive or hyperactive/impulsive presentation, per clinical evaluation and confirmed by the MINI-KID
  5. Clinical Global Impressions-Severity (CGI-S) ≥ 3
  6. ≥ 90th percentile normative value for gender and age on the ADHD RS-IV total score at screening or baseline
  7. 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
  8. Study participant must be able to give assent to participate in the trial
  9. Study participant and legal guardian must be able to speak and understand English
  10. Able to tolerate multiple finger pricks
  11. Willing to comply with all study procedures

Exclusion Criteria:

  1. 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
  2. Cognitively impaired, in the investigator's opinion
  3. 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
  4. Seizure disorder excluding a history of febrile seizures
  5. Thyroid disease
  6. Tourette's disorder or chronic tic disorder (mild medication induced tics are allowed)
  7. Serious cardiac condition including cardiomyopathy, serious arrhythmias, structural cardiac disorders, or severe hypertension
  8. Glaucoma
  9. Current or recent (within the past 6 months) DSM-5 drug dependence or substance abuse (excluding nicotine and caffeine)
  10. 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
  11. Currently treated and satisfied with ADHD medication
  12. Current psychotropic medications other than sedative hypnotics for sleep
  13. Use of atomoxetine, clonidine, guanfacine or a monoamine oxidase inhibitor within 28 days of the baseline visit
  14. Participation in another investigational medication study within 30 days prior to screening
  15. 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
  16. Planned use of prohibited drugs from the baseline visit through the end of the trial
  17. History of allergic reaction or a known or suspected sensitivity to any substance that is contained in the study drugs
  18. Food allergies that are determined by the PI as too severe to be easily accommodated for during the study
  19. Inability to swallow study medication

Sites / Locations

  • Massachusetts General Hospital
  • Center for Psychiatry and Behavioral Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Methylphenidate HCl ER tablets 1

Placebo

Methylphenidate HCl ER tablets 2

Methylphenidate HCl ER for suspension

Arm Description

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

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.

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

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

Outcomes

Primary Outcome Measures

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.
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.
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.
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

Secondary Outcome Measures

Full Information

First Posted
August 24, 2015
Last Updated
November 23, 2019
Sponsor
Massachusetts General Hospital
Collaborators
Food and Drug Administration (FDA), Center for Psychiatry And Behavioral Medicine Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02536105
Brief Title
PK/PD Pediatric ADHD Classroom Study
Official Title
Pharmacokinetic Pharmacodynamic Studies of Methylphenidate Extended Release Products in Pediatric Attention Deficit Hyperactivity Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
May 2016 (Actual)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
July 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Food and Drug Administration (FDA), Center for Psychiatry And Behavioral Medicine Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This is a randomized, double-blind, 4-treatment and 4-period crossover study conducted in a school laboratory environment to evaluate the hour-by-hour behavioral instrument scores and hour-by-hour PK of 3 different extended-release MPH formulations as well as placebo in children with ADHD. The complete study consists of three periods: Screening, Dose Titration and Double-Blind Crossover in a Laboratory Classroom. The double-blind phase will consist of four periods (or four weeks): each week will consist of blinded administration with one of the three active methylphenidate hydrochloride treatments or placebo from Sunday through Saturday. On the last day of each period (Saturday), study participants will be evaluated in a laboratory classroom setting. On Saturdays, the blinded doses of each study drug will be administered at the school site by study staff on the morning of the test laboratory classroom day. On the other days, the medication will be taken in the morning at home.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Hyperactivity Disorder
Keywords
Attention Deficit Hyperactivity Disorder, ADHD

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methylphenidate HCl ER tablets 1
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Methylphenidate HCl ER tablets 2
Arm Type
Active Comparator
Arm Description
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
Arm Title
Methylphenidate HCl ER for suspension
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Methylphenidate HCl ER tablets 1
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Methylphenidate HCl ER tablets 2
Intervention Type
Drug
Intervention Name(s)
Methylphenidate HCl ER for suspension
Primary Outcome Measure Information:
Title
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products
Description
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.
Time Frame
0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day
Title
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products
Description
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.
Time Frame
0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day
Title
Maximum Drug Concentration Observed (Cmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products
Description
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.
Time Frame
0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day
Title
Time to Reach Cmax (Tmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products
Description
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
Time Frame
0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Planned use of prohibited drugs from the baseline visit through the end of the trial History of allergic reaction or a known or suspected sensitivity to any substance that is contained in the study drugs Food allergies that are determined by the PI as too severe to be easily accommodated for during the study Inability to swallow study medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Spencer, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Center for Psychiatry and Behavioral Medicine
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States

12. IPD Sharing Statement

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PK/PD Pediatric ADHD Classroom Study

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