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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Attention Deficit Hyperactivity Disorder (ADHD)

Intervention / Treatment
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* Drug: AR11
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 6 and 12 years of age, inclusive, at the time of Screening. Diagnosed as meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for ADHD. A clinician-administered Clinical Global Impression of Severity (CGI-S) score of 3 or greater. 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: 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. Clinically significant cognitive impairment as assessed in the clinical judgment of the Investigator. 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. Clinically significant abnormal ECG finding or abnormal cardiac finding on physical exam (including presence of a pathologic murmur) at Screening. 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). A history of hypersensitivity or intolerance to any formulation of amphetamine or lisdexamfetamine.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, AR11, classroom design, amphetamine sulfate