Crossover Study to Evaluate the Efficacy of AR11 in Pediatric Patients With ADHD in a Laboratory Classroom Setting

A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to Evaluate the Efficacy of AR11 (Amphetamine Sulfate) in Pediatric Patients (Ages 6-12) With ADHD in a Laboratory Classroom

This is a dose-optimized, randomized, double-blind, placebo-controlled crossover study in approximately 100 pediatric patients (aged 6 to 12 years) with ADHD. Eligible patients will enroll to take open-label AR11 BID and undergo dose optimization activities for 8 weeks. Patients who achieve a stable dose during the dose optimization period will continue participation and will be randomized to take double-blind medication (AR11 or placebo) orally twice daily for 1 week. At the end of each double-blind treatment period, patients will be evaluated for ADHD symptoms in a laboratory classroom setting utilizing SKAMP and PERMP assessments.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Drug: Placebo; Drug: AR11

Detailed Description

This is a dose-optimized, randomized, double-blind, placebo-controlled crossover study in approximately 100 pediatric patients (aged 6 to 12 years) with ADHD. Eligible patients will enroll in the study to take open-label AR11 twice daily and undergo dose optimization activities for 8 weeks. Patients who achieve a stable dose during the dose optimization period will continue participation and will be randomized to take double-blind medication (AR11 or placebo) orally twice daily for 1 week. At the end of the first double-blind treatment period, patients will be evaluated for ADHD symptoms in a laboratory classroom setting utilizing SKAMP and PERMP assessments. At the end of the second double blind treatment period, patients will be evaluated for ADHD symptoms in a second laboratory classroom setting utilizing SKAMP and PERMP assessments.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Bradenton, Florida, United States, 34201
      • Florida Clinical Research Center, LLC.
    • Maitland, Florida, United States, 32751
      • Florida Clinical Research Center, LLC
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioral Medicine, Inc.
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Texas
    • Houston, Texas, United States, 77007
      • Bayou City Research Ltd.
    • Houston, Texas, United States, 79423
      • Westex Clinical Investigations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female between 6 and 12 years of age, inclusive, at the time of Screening.
2. Diagnosed as meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for ADHD.
3. A clinician-administered Clinical Global Impression of Severity (CGI-S) score of 3 or greater.
4. An ADHD Rating Scale (ADHD-RS) score at Screening and Baseline greater than or equal to the 90th percentile normative values for gender and age in at least one of the following categories: hyperactive-impulsive subscale, inattentive subscale, or total score.

Exclusion Criteria:

1. Secondary or co-morbid diagnoses other than ADHD, with the exception of simple phobias, oppositional defiant disorder, elimination disorders, motor skills disorders, communication disorders, learning disorders, adjustment disorders, and sleep disorders if, in the opinion of the investigator, the associated symptoms do not confound assessment of safety or efficacy.
2. Clinically significant cognitive impairment as assessed in the clinical judgment of the Investigator.
3. History of any of the following medical disorders: seizure disorder (excluding a history of febrile seizures), structural cardiac disorders, serious cardiac conditions, hypertension, untreated thyroid disease, glaucoma, Tourette's disorder, or chronic tics.
4. Clinically significant abnormal ECG finding or abnormal cardiac finding on physical exam (including presence of a pathologic murmur) at Screening.
5. Use of any psychotropic medication (sedative hypnotics prescribed as a sleep aid at a stable dose for at least 30 days prior to Baseline, at bedtime only, are allowed during the study).
6. A history of hypersensitivity or intolerance to any formulation of amphetamine or lisdexamfetamine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AR11 (amphetamine sulfate) (1 week) - double blind; AR11, administered orally, BID, for one week (crossover to placebo administration week 2)	Drug: AR11; Other Names: amphetamine sulfate
Placebo Comparator: Placebo (1 week) - double blind; Placebo, administered orally, BID, for one week (crossover to AR11 administration week 2)	Drug: Placebo; Other Names: matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SKAMP-Combined Scores	Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale [SKAMP]-combined scores measured during Laboratory Classroom Days. The SKAMP scale is a validated subjective measure of ADHD symptoms in a laboratory classroom, comprised of 13 items on which subjects are rated according to a 7 point scale (0=normal to 6=maximal impairment); maximum score 78. The SKAMP-combined score is obtained by summing the rating values for each of the 13 items, whereby the higher the SKAMP score, the greater the impairment.	2 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SKAMP-Combined Scores	Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale [SKAMP]-combined scores measured during Laboratory Classroom Days. The SKAMP scale is a validated subjective measure of ADHD symptoms in a laboratory classroom, comprised of 13 items on which subjects are rated according to a 7 point scale (0=normal to 6=maximal impairment); maximum score 78. The SKAMP-combined score is obtained by summing the rating values for each of the 13 items, whereby the higher the SKAMP score, the greater the impairment.	0.75, 4, 6, 8, 10 hours post-dose
SKAMP Subscale - Attention Scores	The SKAMP scale is a validated subjective measure of ADHD symptoms. It is comprised of 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment). The SKAMP-Attention subscale score is comprised of four of the 13 items with a maximum score of 24.	0.75, 2, 4, 6, 8, and 10 hours post-dose
SKAMP Subscale - Deportment Scores	The SKAMP scale is a validated subjective measure of ADHD symptoms. It is comprised of 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment). The SKAMP-Deportment subscale score is comprised of four of the 13 items with a maximum score of 24.	0.75, 2, 4, 6, 8, and 10 hours post-dose
PERM-P Scores - Number of Problems Attempted	Permanent Product Measure of Performance (PERMP) assessments measured during Laboratory Classroom Days. The PERMP is an individualized, five-page math exam consisting of 400 problems. Subjects are instructed to complete as many math problems as possible in 10 minutes. Performance is evaluated using the number of problems attempted (maximum score = 400) and the number of problems correct (maximum score = 400).	0.75, 2, 4, 6, 8, and 10 hours post-dose
PERM-P Scores - Number of Problems Correct	Permanent Product Measure of Performance (PERMP) assessments measured during Laboratory Classroom Days. The PERMP is an individualized, five-page math exam consisting of 400 problems. Subjects are instructed to complete as many math problems as possible in 10 minutes. Performance is evaluated using the number of problems attempted (maximum score = 400) and the number of problems correct (maximum score = 400).	0.75, 2, 4, 6, 8, and 10 hours post-dose

Collaborators and Investigators

• Sponsor: Arbor Pharmaceuticals, Inc.
• Investigators: Study Director: Laurence Downey, MD, Arbor Pharmaceuticals, LLC.

Publications and helpful links

General Publications

• Childress AC, Brams M, Cutler AJ, Kollins SH, Northcutt J, Padilla A, Turnbow JM. The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study. J Child Adolesc Psychopharmacol. 2015 Jun;25(5):402-14. doi: 10.1089/cap.2014.0176. Epub 2015 Feb 18.
• Childress AC, Newcorn JH, Cutler AJ. Gender Effects in the Efficacy of Racemic Amphetamine Sulfate in Children with Attention-Deficit/Hyperactivity Disorder. Adv Ther. 2019 Jun;36(6):1370-1387. doi: 10.1007/s12325-019-00942-5. Epub 2019 Apr 10.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 11, 2013
• First Submitted That Met QC Criteria: November 11, 2013
• First Posted (Estimate): November 18, 2013

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: ADHD; AR11; classroom design; amphetamine sulfate
• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Amphetamine
• Other Study ID Numbers: AR11.001