ADHD, Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Attention deficit, Hyperactivity, Impulsivity, Inattention
Brief summary
The time course of response following one dose of a new methylphenidate hydrochloride extended release capsule is studied in children 6-12 years in a simulated laboratory classroom setting. Biphentin methylphenidate hydrochloride extended release capsule has been formulated for daily dosing to provide treatment of a child with Attention deficit hyperactivity disorder (ADHD) for the substantial day.
Detailed description
Biphentin methylphenidate hydrochloride (HCl) extended release (ER) capsules is provided in multiple strengths of 10, 15, 20, 30, 40, 50, and 60 mg to be administered once daily. Once daily dosing is intended to provide treatment for the substantial day. For current analog classroom study each eligible subject will be optimized at 15, 20, 30, or 40 mg in a timeframe of five weekly periods. In the sixth week each subject will be randomized double-blind to receive either active comparator at the optimized dose or placebo comparator treatment. The first classroom session will be held at the end of the week, when efficacy measurements including Swanson, Kotkin, Agler, M-Flynn, Pelham Rating Scale (SKAMP) and Permanent Product Measure of Performance (PERMP) tests will be administered. At the beginning of the following week, the subjects will be crossed-over to the corresponding active comparator or placebo comparator treatment. The second classroom session will be held at the end of the second double-blind week, when the same efficacy measurements will be administered. Various safety and tolerability, and quality of life assessments will be conducted.
Interventions
An optimized dose of Methylphenidate Hydrochloride Extended Release Capsules 15, 20, 30 or 40 mg to be dosed once daily
DRUGPlacebo
Capsule without active drug
Sponsors
Rhodes Pharmaceuticals, L.P.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
All subjects entered the Open-Label Dose optimization phase and were titrated until an optimized dose of Methylphenidate hydrochloride Extended Release capsule was achieved. Completing subjects then entered the randomized Double-blind Phase (crossover).
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females ages 6 to 12. 2. ADHD diagnosis with ADHD Rating Scale - 4th Edition scores ≥ 90th percentile. 3. In need of treatment for ADHD and able to have 2-day washout from previous medication. 4. Females of child-bearing potential not pregnant and practice birth control. 5. Subject and parent/guardian willing to comply with protocol. 6. Signed consent and assent.
Exclusion criteria
1. Estimated Full Scale intellectual level below 80 using Wechsler Abbreviated Scale of Intelligence. 2. Current primary psychiatric diagnosis of: severe anxiety disorder, conduct disorder, psychotic disorders, pervasive developmental disorder, eating disorder, obsessive-compulsive disorder, major depressive disorder, bipolar disorder, substance use disorder, chronic tic disorder, personal or family history of Tourette's Syndrome. 3. Chronic medical illnesses: seizure, hypertension, thyroid disease, cardiac, family history of sudden death, glaucoma. 4. Use of psychotropic CNS meds having effect exceeding 14 days from screening. 5. Planned use of prohibited drugs. 6. Is pregnant or breast-feeding. 7. Significant ECG or laboratory abnormalities. 8. Experimental drug or medical device within 30 days prior to screening. 9. Hypersensitivity to methylphenidate. 10. Inability or unwillingness to comply with protocol. 11. Well controlled on current ADHD treatment. 12. Inability to take oral capsules.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales | Average over all post-dose time points (1.0, 2.0, 3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12 hours) | Comparison of Swanson, Kotkin, Alger, M-Flynn and Pelham (SKAMP) Combined, Attention, and Deportment Scales following drug dose versus placebo. The SKAMP scale is a validated rating scale that assesses behavioral symptoms of ADHD in a classroom setting using a 7-point impairment scale (0 = none through 6 = maximal impairment). The SKAMP total score comprises 13 items, with individual total scores ranging from 0 to 78 (lower scores mean better outcome). The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, and staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention and evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | 12 hours post-dose | Comparison of PERMP measurement scores following drug dose versus placebo (math-correct). The Permanent Product Measure of Performance (PERMP), is a 5-page test consisting of 80 math problems per page (total of 400 problems) and evaluates effortful performance in the classroom as a measure of efficacy. Participants are instructed to work at their seats and to complete as many problems as possible in 10 minutes. The appropriate level of difficulty for each student was determined previously based on results of a math pretest administered at screening. Performance was evaluated using PERMP-A) and PERMP-C scores. Measures obtained from these tests include the number of problems attempted (Math-Attempted; PERMP-A) and the number of problems answered correctly (Math-Correct; PERMP-C). Higher scores are better. The responses are reviewed by comparing them to an answer template, and they are triple-checked for accuracy |
Countries
United States
Participant flow
Recruitment details
Study Start Date: 19 January 2011 (First subject screened) Double-Blind Phase Completion Date: 18 June 2011 (Last subject visit in Double-Blind phase) Compassionate Use Phase Completion Date: 13 March 2013 (Last subject visit in Compassionate Use phase)
Pre-assignment details
Approximately 27 otherwise healthy pediatric subjects (aged 6 to 12) diagnosed with ADHD by DSM-IV-TR™ criteria were planned to participate in the study so that approximately 24 subjects would complete the Double-Blind phase. Subjects were to be randomized into 2 sequences with approximately 12 subjects in each sequence
Participants by arm
| Arm | Count |
|---|---|
| Safety Population All subjects entering open label dose optimization phase (Safety Population) and received at least one dose of study drug | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 0 |
| First Intervention | Lack of Efficacy | 0 | 1 |
| First Intervention | Physician Decision | 0 | 1 |
| First Intervention | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Categorical <=18 years | 26 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 8.7 Years STANDARD_DEVIATION 1.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 26 | 7 / 21 | 3 / 22 |
| serious Total, serious adverse events | 0 / 26 | 0 / 21 | 0 / 22 |
Outcome results
Primary
Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales
Comparison of Swanson, Kotkin, Alger, M-Flynn and Pelham (SKAMP) Combined, Attention, and Deportment Scales following drug dose versus placebo. The SKAMP scale is a validated rating scale that assesses behavioral symptoms of ADHD in a classroom setting using a 7-point impairment scale (0 = none through 6 = maximal impairment). The SKAMP total score comprises 13 items, with individual total scores ranging from 0 to 78 (lower scores mean better outcome). The SKAMP-D subscale evaluates deportment, including interacting with other children, interacting with adults, remaining quiet according to classroom rules, and staying seated according to classroom rules. The SKAMP-A subscale is a measure of attention and evaluates getting started on assignments, sticking with tasks, attending to an activity, and making activity transitions. The SKAMP quality of work subscale includes 3 items: completing assigned work, performing work accurately, and being careful and neat while writing or drawing.
Time frame: Average over all post-dose time points (1.0, 2.0, 3.0, 4.5, 6.0, 7.5, 9.0, 10.5, and 12 hours)
Population: 20 subjects were in the evaluable population, defined as subjects who completed SKAMP assessments for all the study time points on study days 35 and 42, and who received the scheduled treatment in both periods during the double-blind phase. Two (2) subjects were excluded from the evaluable population due to protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate HCl ER Capsules | Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales | 1.46 units on a scale | Standard Deviation 0.52 |
| Capsule Without Active Drug | Comparison Following Treatment Between Drug and Placebo Using Evaluation by SKAMP Combined, Attention, and Deportment Scales | 2.03 units on a scale | Standard Deviation 0.92 |
p-value: <0.01ANCOVA
Secondary
Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations
Comparison of PERMP measurement scores following drug dose versus placebo (math-correct). The Permanent Product Measure of Performance (PERMP), is a 5-page test consisting of 80 math problems per page (total of 400 problems) and evaluates effortful performance in the classroom as a measure of efficacy. Participants are instructed to work at their seats and to complete as many problems as possible in 10 minutes. The appropriate level of difficulty for each student was determined previously based on results of a math pretest administered at screening. Performance was evaluated using PERMP-A) and PERMP-C scores. Measures obtained from these tests include the number of problems attempted (Math-Attempted; PERMP-A) and the number of problems answered correctly (Math-Correct; PERMP-C). Higher scores are better. The responses are reviewed by comparing them to an answer template, and they are triple-checked for accuracy
Time frame: 12 hours post-dose
Population: 20 subjects were in the evaluable population, defined as subjects who completed PERMP assessments for all the study time points on study days 35 and 42, and who received the scheduled treatment in both periods during the double-blind phase. Two (2) subjects were excluded from the evaluable population due to protocol deviations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Methylphenidate HCl ER Capsules | Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | PERMP-A | 92.85 Number of Problems | Standard Deviation 48.01 |
| Methylphenidate HCl ER Capsules | Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | PERMP-C | 86.85 Number of Problems | Standard Deviation 49.29 |
| Capsule Without Active Drug | Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | PERMP-A | 80.30 Number of Problems | Standard Deviation 55.31 |
| Capsule Without Active Drug | Comparison Following Treatment With Drug or Placebo Using PERMP (Permanent Product of Arithmetic) Evaluations | PERMP-C | 74.80 Number of Problems | Standard Deviation 57.41 |
p-value: <0.01ANCOVA