Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, children, laboratory classroom, Attention Deficit Hyperactivity Disorder
Brief summary
This study compared the efficacy of dex-methylphenidate extended release 20 mg versus placebo during an 8-hour laboratory classroom day.
Interventions
DRUGDex-methylphenidate hydrochloride extended-release (Focalin XR)
20 mg capsule orally once a day for 7 days
DRUGPlacebo
orally once a day for 7 days
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects aged 6-12 years, inclusive. * Subjects meeting the DSM-IV criteria for ADHD of any type, as established by the K-SADS-PL (Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version). If a DSM-IV-defined ADHD diagnosis is difficult to establish due to possible co-morbidity, the subject will not be enrolled into the study. * Subjects should be on a stabilized total daily dose or nearest equivalent of 40-60 mg methylphenidate or 20-30 mg of d-methylphenidate for at least two weeks prior to screening visit (Concerta® 36 mg and 54 mg is allowable)
Exclusion criteria
* Parent or guardian unable or unwilling to complete the Conner's ADHD/DSM-IV Scale for Parents (CADS-P) and the Daily Diary Card * Diagnosed with a tic disorder or Tourette's syndrome * History of seizure disorder * The presence of a known medical condition that would preclude the use of methylphenidate. A history (within the past year) or presence of clinically significant cardiovascular, cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological, hematological, endocrine, or neurological disease * ALT, AST, GGPT or serum creatinine greater then 2X the ULN at Screening * A history of psychiatric illness or substance use disorder (e.g., schizophrenia, bipolar disorder, autism, abuse or dependence, depression, severe Conduct Disorder or severe Oppositional defiant disorder) * Subjects who have participated in an investigational trial within the past 4 weeks (28 days) are excluded * Subjects who are currently taking antidepressants or other psychotropic medication * Subjects who have initiated psychotherapy during the three months prior to randomization * Subjects with a positive urine drug screen * Subjects who have a history of poor response or intolerance to methylphenidate or d-methylphenidate Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Pre-dose (0 hr [Hour]) on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 Hour During the 8- Hour Laboratory Classroom Day | 0 hr and 0.5 hr post-dose | SKAMP rating scale is comprised of 13 questions (7 questions on attention and 6 questions on deportment) evaluating classroom behavior; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 78. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 0, 1, 2, 4, 6, and 8 hr | SKAMP rating scale is comprised of 13 questions (7 questions on attention and 6 questions on deportment) evaluating classroom behavior; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 78. |
| Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 0, 0.5, 1, 2, 4, 6, and 8 hours | SKAMP attention sub-scale is comprised of 7 questions evaluating concentration in the classroom; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 42. |
| Change From Pre-dose in SKAMP Deportment Score | 0, 0.5, 1, 2, 4, 6 and 8 hours | SKAMP deportment sub-scale is comprised of 6 questions on behavior in the classroom; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 36. |
| Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 0, 0.5, 1, 2, 4, 6 and 8 hours | Number of math questions attempted within a 10 minute period. |
| Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 0, 0.5, 1, 2, 4, 6 and 8 hours | Number of math questions answered correctly within a 10 minute period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) Then Placebo Period 1: One 20 mg capsule of Focalin XR taken once daily in the morning for one week followed by Period 2: one week of placebo taken once daily in the morning. | 44 |
| Placebo Then Dex-methylphenidate Hydrochloride (Focalin XR) Period 1: One week of placebo taken once daily in the morning followed by Period 2: one week of one 20 mg capsule of Focalin XR taken once daily in the morning. | 42 |
| Total | 86 |
Baseline characteristics
| Characteristic | Dex-methylphenidate Hydrochloride (Focalin XR) Then Placebo | Placebo Then Dex-methylphenidate Hydrochloride (Focalin XR) | Total |
|---|---|---|---|
| Age Continuous | 9.5 years STANDARD_DEVIATION 2 | 9.4 years STANDARD_DEVIATION 1.4 | 9.5 years STANDARD_DEVIATION 1.7 |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 33 Participants |
| Sex: Female, Male Male | 28 Participants | 25 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 86 | 0 / 86 |
| serious Total, serious adverse events | 0 / 86 | 0 / 86 |
Outcome results
Primary
Change From Pre-dose (0 hr [Hour]) on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 Hour During the 8- Hour Laboratory Classroom Day
SKAMP rating scale is comprised of 13 questions (7 questions on attention and 6 questions on deportment) evaluating classroom behavior; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 78.
Time frame: 0 hr and 0.5 hr post-dose
Population: Intent to Treat (ITT) population: All randomized patients who had at least one dose of study medication and who had at least one post-dose efficacy measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr [Hour]) on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 Hour During the 8- Hour Laboratory Classroom Day | -0.969 score on a scale | Standard Error 0.909 |
| Placebo | Change From Pre-dose (0 hr [Hour]) on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 Hour During the 8- Hour Laboratory Classroom Day | 3.336 score on a scale | Standard Error 0.907 |
Secondary
Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8)
Number of math questions attempted within a 10 minute period.
Time frame: 0, 0.5, 1, 2, 4, 6 and 8 hours
Population: Intent to Treat (ITT) population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 0.5 hour | 6.93 questions attempted | Standard Error 2.96 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 1 hour | 33.26 questions attempted | Standard Error 3.66 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 2 hours | 45.52 questions attempted | Standard Error 3.61 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 4 hours | 45.01 questions attempted | Standard Error 3.6 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 6 hours | 37.33 questions attempted | Standard Error 3.82 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 8 hours | 44.04 questions attempted | Standard Error 3.5 |
| Placebo | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 6 hours | -16.70 questions attempted | Standard Error 3.84 |
| Placebo | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 0.5 hour | -4.74 questions attempted | Standard Error 2.96 |
| Placebo | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 4 hours | -7.42 questions attempted | Standard Error 3.6 |
| Placebo | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 1 hour | -12.18 questions attempted | Standard Error 3.66 |
| Placebo | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 8 hours | -10.08 questions attempted | Standard Error 3.5 |
| Placebo | Change From Pre-dose (0 hr.) in Permanent Product Measure of Performance (PERMP) Math Test-Attempted Scores at All Timepoints (0.5, 1, 2, 4, 6, 8) | 2 hours | -10.19 questions attempted | Standard Error 3.61 |
Secondary
Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8)
SKAMP rating scale is comprised of 13 questions (7 questions on attention and 6 questions on deportment) evaluating classroom behavior; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 78.
Time frame: 0, 1, 2, 4, 6, and 8 hr
Population: Intent to Treat (ITT) population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 2 hours | -11.573 score on a scale | Standard Error 0.856 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 6 hours | -10.622 score on a scale | Standard Error 0.95 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 4 hours | -11.395 score on a scale | Standard Error 0.847 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 8 hours | -10.260 score on a scale | Standard Error 0.988 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 1 hour | -6.358 score on a scale | Standard Error 0.993 |
| Placebo | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 8 hours | 3.621 score on a scale | Standard Error 0.986 |
| Placebo | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 1 hour | 5.670 score on a scale | Standard Error 0.991 |
| Placebo | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 2 hours | 5.467 score on a scale | Standard Error 0.854 |
| Placebo | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 4 hours | 3.925 score on a scale | Standard Error 0.844 |
| Placebo | Change From Pre-dose (0 hr) in SKAMP Combined Score at All Times Excluding the 0.5 Hour Timepoint (Hours 1, 2, 4, 6, 8) | 6 hours | 5.346 score on a scale | Standard Error 0.952 |
Secondary
Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test
Number of math questions answered correctly within a 10 minute period.
Time frame: 0, 0.5, 1, 2, 4, 6 and 8 hours
Population: Intent to Treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 0.5 hour | 7.10 questions correct | Standard Error 2.72 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 1 hour | 31.10 questions correct | Standard Error 3.34 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 2 hours | 44.92 questions correct | Standard Error 3.44 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 4 hours | 43.64 questions correct | Standard Error 3.37 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 6 hours | 37.78 questions correct | Standard Error 3.55 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 8 hours | 43.37 questions correct | Standard Error 3.4 |
| Placebo | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 6 hours | -16.90 questions correct | Standard Error 3.57 |
| Placebo | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 0.5 hour | -5.96 questions correct | Standard Error 2.72 |
| Placebo | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 4 hours | -7.52 questions correct | Standard Error 3.37 |
| Placebo | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 1 hour | -13.21 questions correct | Standard Error 3.34 |
| Placebo | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 8 hours | -11.44 questions correct | Standard Error 3.4 |
| Placebo | Change From Pre-dose in Number of Math Questions Answered Correctly on the Permanent Product Measure of Performance (PERMP) Math Test | 2 hours | -11.09 questions correct | Standard Error 3.44 |
Secondary
Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8)
SKAMP attention sub-scale is comprised of 7 questions evaluating concentration in the classroom; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 42.
Time frame: 0, 0.5, 1, 2, 4, 6, and 8 hours
Population: Intent to Treat (ITT) population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 0.5 hour | -0.825 score on a scale | Standard Error 0.524 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 1 hour | -4.208 score on a scale | Standard Error 0.589 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 2 hours | -6.591 score on a scale | Standard Error 0.507 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 4 hours | -6.722 score on a scale | Standard Error 0.506 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 6 hours | -5.819 score on a scale | Standard Error 0.582 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 8 hours | -6.061 score on a scale | Standard Error 0.584 |
| Placebo | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 6 hours | 2.715 score on a scale | Standard Error 0.58 |
| Placebo | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 0.5 hour | 0.862 score on a scale | Standard Error 0.52 |
| Placebo | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 4 hours | 1.183 score on a scale | Standard Error 0.503 |
| Placebo | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 1 hour | 2.304 score on a scale | Standard Error 0.584 |
| Placebo | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 8 hours | 1.415 score on a scale | Standard Error 0.58 |
| Placebo | Change From Pre-dose in SKAMP Attention Score at All Timepoints (0.5, 1, 2, 4, 6, 8) | 2 hours | 2.465 score on a scale | Standard Error 0.504 |
Secondary
Change From Pre-dose in SKAMP Deportment Score
SKAMP deportment sub-scale is comprised of 6 questions on behavior in the classroom; answers to each question range from 0 (normal, no impairment) to 6 (maximum impairment) for a total possible combined score of 0 to 36.
Time frame: 0, 0.5, 1, 2, 4, 6 and 8 hours
Population: Intent to Treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Deportment Score | 0.5 hour | 0.127 score on a scale | Standard Error 0.55 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Deportment Score | 1 hour | -1.863 score on a scale | Standard Error 0.564 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Deportment Score | 2 hours | -4.850 score on a scale | Standard Error 0.499 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Deportment Score | 4 hours | -4.420 score on a scale | Standard Error 0.526 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Deportment Score | 6 hours | -4.614 score on a scale | Standard Error 0.541 |
| Dex-methylphenidate Hydrochloride (Focalin XR) | Change From Pre-dose in SKAMP Deportment Score | 8 hours | -3.939 score on a scale | Standard Error 0.56 |
| Placebo | Change From Pre-dose in SKAMP Deportment Score | 6 hours | 2.393 score on a scale | Standard Error 0.541 |
| Placebo | Change From Pre-dose in SKAMP Deportment Score | 0.5 hour | 2.226 score on a scale | Standard Error 0.55 |
| Placebo | Change From Pre-dose in SKAMP Deportment Score | 4 hours | 2.511 score on a scale | Standard Error 0.526 |
| Placebo | Change From Pre-dose in SKAMP Deportment Score | 1 hour | 3.103 score on a scale | Standard Error 0.564 |
| Placebo | Change From Pre-dose in SKAMP Deportment Score | 8 hours | 1.969 score on a scale | Standard Error 0.56 |
| Placebo | Change From Pre-dose in SKAMP Deportment Score | 2 hours | 2.881 score on a scale | Standard Error 0.499 |