Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD, AR11, classroom design, amphetamine sulfate
Brief summary
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
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.
Interventions
DRUGAR11
DRUGPlacebo
Sponsors
Arbor Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SKAMP-Combined Scores | 2 hours post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SKAMP-Combined Scores | 0.75, 4, 6, 8, 10 hours post-dose | 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. |
| SKAMP Subscale - Attention Scores | 0.75, 2, 4, 6, 8, and 10 hours post-dose | 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. |
| SKAMP Subscale - Deportment Scores | 0.75, 2, 4, 6, 8, and 10 hours post-dose | 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. |
| PERM-P Scores - Number of Problems Attempted | 0.75, 2, 4, 6, 8, and 10 hours post-dose | 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). |
| PERM-P Scores - Number of Problems Correct | 0.75, 2, 4, 6, 8, and 10 hours post-dose | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AR11 (1 Week) Then Placebo (1 Week) - Double Blind AR11, administered orally, BID for one week (crossover to placebo administration week 2) | 47 |
| Placebo (1 Week) Then AR11 (1 Week) - Double Blind Placebo, administered orally, BID for one week (crossover to AR11 administration week 2) | 50 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | AR11 (1 Week) Then Placebo (1 Week) - Double Blind | Total | Placebo (1 Week) Then AR11 (1 Week) - Double Blind |
|---|---|---|---|
| Age, Continuous | 9.6 years STANDARD_DEVIATION 1.97 | 9.6 years STANDARD_DEVIATION 1.86 | 9.6 years STANDARD_DEVIATION 1.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 33 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 30 Participants | 58 Participants | 28 Participants |
| Region of Enrollment United States | 47 participants | 97 participants | 50 participants |
| Sex: Female, Male Female | 18 Participants | 38 Participants | 20 Participants |
| Sex: Female, Male Male | 29 Participants | 59 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 97 | 6 / 97 |
| serious Total, serious adverse events | 0 / 97 | 0 / 97 |
Outcome results
Primary
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.
Time frame: 2 hours post-dose
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AR11 (Amphetamine Sulfate) | SKAMP-Combined Scores | 10.0 units on a scale | Standard Deviation 8.24 |
| Placebo | SKAMP-Combined Scores | 17.8 units on a scale | Standard Deviation 1.94 |
p-value: <0.0001Mixed Models Analysis
Secondary
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).
Time frame: 0.75, 2, 4, 6, 8, and 10 hours post-dose
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Attempted | 2.0 hours post-dose | 113.4 number of problems attempted | Standard Deviation 51.27 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Attempted | 0.75 hours post-dose | 111.6 number of problems attempted | Standard Deviation 53.53 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Attempted | 4.0 hours post-dose | 113.2 number of problems attempted | Standard Deviation 56.28 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Attempted | 6.0 hours post-dose | 101.3 number of problems attempted | Standard Deviation 54.26 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Attempted | 8.0 hours post-dose | 98.2 number of problems attempted | Standard Deviation 56.11 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Attempted | 10.0 hours post-dose | 95.2 number of problems attempted | Standard Deviation 55.53 |
| Placebo | PERM-P Scores - Number of Problems Attempted | 8.0 hours post-dose | 76.4 number of problems attempted | Standard Deviation 47.74 |
| Placebo | PERM-P Scores - Number of Problems Attempted | 6.0 hours post-dose | 74.9 number of problems attempted | Standard Deviation 43.08 |
| Placebo | PERM-P Scores - Number of Problems Attempted | 0.75 hours post-dose | 91.2 number of problems attempted | Standard Deviation 47.35 |
| Placebo | PERM-P Scores - Number of Problems Attempted | 2.0 hours post-dose | 85.7 number of problems attempted | Standard Deviation 46.66 |
| Placebo | PERM-P Scores - Number of Problems Attempted | 10.0 hours post-dose | 76.3 number of problems attempted | Standard Deviation 45.27 |
| Placebo | PERM-P Scores - Number of Problems Attempted | 4.0 hours post-dose | 85.1 number of problems attempted | Standard Deviation 45.89 |
p-value: <0.0001Mixed Models Analysis
Secondary
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).
Time frame: 0.75, 2, 4, 6, 8, and 10 hours post-dose
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Correct | 0.75 hours post-dose | 104.5 number of problems correct | Standard Deviation 54.49 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Correct | 2.0 hours post-dose | 107.1 number of problems correct | Standard Deviation 53.15 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Correct | 4.0 hours post-dose | 107.0 number of problems correct | Standard Deviation 57.46 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Correct | 6.0 hours post-dose | 95.6 number of problems correct | Standard Deviation 55.43 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Correct | 8.0 hours post-dose | 92.7 number of problems correct | Standard Deviation 57.28 |
| AR11 (Amphetamine Sulfate) | PERM-P Scores - Number of Problems Correct | 10.0 hours post-dose | 89.9 number of problems correct | Standard Deviation 55.29 |
| Placebo | PERM-P Scores - Number of Problems Correct | 8.0 hours post-dose | 71.5 number of problems correct | Standard Deviation 47.43 |
| Placebo | PERM-P Scores - Number of Problems Correct | 0.75 hours post-dose | 83.9 number of problems correct | Standard Deviation 46.96 |
| Placebo | PERM-P Scores - Number of Problems Correct | 6.0 hours post-dose | 70.5 number of problems correct | Standard Deviation 43.23 |
| Placebo | PERM-P Scores - Number of Problems Correct | 2.0 hours post-dose | 78.9 number of problems correct | Standard Deviation 44.62 |
| Placebo | PERM-P Scores - Number of Problems Correct | 10.0 hours post-dose | 72.3 number of problems correct | Standard Deviation 45.19 |
| Placebo | PERM-P Scores - Number of Problems Correct | 4.0 hours post-dose | 79.9 number of problems correct | Standard Deviation 45.56 |
p-value: <0.0001Mixed Models Analysis
Secondary
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.
Time frame: 0.75, 4, 6, 8, 10 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR11 (Amphetamine Sulfate) | SKAMP-Combined Scores | 0.75 hours post-dose | 11.8 units on a scale | Standard Deviation 10.56 |
| AR11 (Amphetamine Sulfate) | SKAMP-Combined Scores | 8 hours post-dose | 16.0 units on a scale | Standard Deviation 11.76 |
| AR11 (Amphetamine Sulfate) | SKAMP-Combined Scores | 4 hours post-dose | 11.6 units on a scale | Standard Deviation 10.04 |
| AR11 (Amphetamine Sulfate) | SKAMP-Combined Scores | 10 hours post-dose | 16.5 units on a scale | Standard Deviation 11.08 |
| AR11 (Amphetamine Sulfate) | SKAMP-Combined Scores | 6 hours post-dose | 14.5 units on a scale | Standard Deviation 10.38 |
| Placebo | SKAMP-Combined Scores | 10 hours post-dose | 20.8 units on a scale | Standard Deviation 13.33 |
| Placebo | SKAMP-Combined Scores | 0.75 hours post-dose | 17.3 units on a scale | Standard Deviation 11.38 |
| Placebo | SKAMP-Combined Scores | 6 hours post-dose | 20.2 units on a scale | Standard Deviation 11.28 |
| Placebo | SKAMP-Combined Scores | 8 hours post-dose | 22.0 units on a scale | Standard Deviation 12.33 |
| Placebo | SKAMP-Combined Scores | 4 hours post-dose | 19.8 units on a scale | Standard Deviation 11.92 |
p-value: <0.0001Mixed Models Analysis
Secondary
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.
Time frame: 0.75, 2, 4, 6, 8, and 10 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Attention Scores | 2.0 hours post-dose | 1.9 units on a scale | Standard Deviation 2.26 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Attention Scores | 6.0 hours post-dose | 2.3 units on a scale | Standard Deviation 2.43 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Attention Scores | 8.0 hours post-dose | 2.8 units on a scale | Standard Deviation 2.8 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Attention Scores | 4.0 hours post-dose | 2.2 units on a scale | Standard Deviation 2.68 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Attention Scores | 10.0 hours post-dose | 3.2 units on a scale | Standard Deviation 3.15 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Attention Scores | 0.75 hours post-dose | 2.2 units on a scale | Standard Deviation 2.64 |
| Placebo | SKAMP Subscale - Attention Scores | 10.0 hours post-dose | 4.0 units on a scale | Standard Deviation 3.59 |
| Placebo | SKAMP Subscale - Attention Scores | 0.75 hours post-dose | 3.4 units on a scale | Standard Deviation 3.06 |
| Placebo | SKAMP Subscale - Attention Scores | 2.0 hours post-dose | 3.4 units on a scale | Standard Deviation 3.1 |
| Placebo | SKAMP Subscale - Attention Scores | 4.0 hours post-dose | 4.0 units on a scale | Standard Deviation 3.04 |
| Placebo | SKAMP Subscale - Attention Scores | 6.0 hours post-dose | 3.6 units on a scale | Standard Deviation 2.95 |
| Placebo | SKAMP Subscale - Attention Scores | 8.0 hours post-dose | 4.1 units on a scale | Standard Deviation 3.01 |
p-value: <0.0001Mixed Models Analysis
Secondary
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.
Time frame: 0.75, 2, 4, 6, 8, and 10 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Deportment Scores | 8.0 hours post-dose | 3.5 units on a scale | Standard Deviation 4.38 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Deportment Scores | 0.75 hours post-dose | 2.1 units on a scale | Standard Deviation 3.53 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Deportment Scores | 6.0 hours post-dose | 3.1 units on a scale | Standard Deviation 4.21 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Deportment Scores | 2.0 hours post-dose | 1.6 units on a scale | Standard Deviation 2.79 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Deportment Scores | 10.0 hours post-dose | 3.1 units on a scale | Standard Deviation 3.72 |
| AR11 (Amphetamine Sulfate) | SKAMP Subscale - Deportment Scores | 4.0 hours post-dose | 2.1 units on a scale | Standard Deviation 3.47 |
| Placebo | SKAMP Subscale - Deportment Scores | 10.0 hours post-dose | 4.9 units on a scale | Standard Deviation 5.21 |
| Placebo | SKAMP Subscale - Deportment Scores | 6.0 hours post-dose | 4.3 units on a scale | Standard Deviation 4.51 |
| Placebo | SKAMP Subscale - Deportment Scores | 8.0 hours post-dose | 4.9 units on a scale | Standard Deviation 4.8 |
| Placebo | SKAMP Subscale - Deportment Scores | 4.0 hours post-dose | 4.7 units on a scale | Standard Deviation 4.86 |
| Placebo | SKAMP Subscale - Deportment Scores | 0.75 hours post-dose | 3.9 units on a scale | Standard Deviation 4.82 |
| Placebo | SKAMP Subscale - Deportment Scores | 2.0 hours post-dose | 4.0 units on a scale | Standard Deviation 4.58 |
p-value: <0.0001Mixed Models Analysis