Time Course of Response to Methylphenidate HCl ER Capsules in Children 6 to 12 Years With ADHD in Classroom Setting

Study Overview
=================
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.

Official Title
-----------------
A Randomized, Double-Blind Study of the Time Course of Response to Biphentin® Methylphenidate Hydrochloride ER Capsules Compared to Placebo in Children 6 to 12 Years With Attention Deficit Hyperactivity Disorder in Analog Classroom Setting

Conditions
-----------------
Attention Deficit Hyperactivity Disorder, ADHD

Intervention / Treatment
-----------------
* Drug: Methylphenidate Hydrochloride Extended Release Capsule
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females ages 6 to 12. ADHD diagnosis with ADHD Rating Scale - 4th Edition scores ≥ 90th percentile. In need of treatment for ADHD and able to have 2-day washout from previous medication. Females of child-bearing potential not pregnant and practice birth control. Subject and parent/guardian willing to comply with protocol. Signed consent and assent. Exclusion Criteria: Estimated Full Scale intellectual level below 80 using Wechsler Abbreviated Scale of Intelligence. 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. Chronic medical illnesses: seizure, hypertension, thyroid disease, cardiac, family history of sudden death, glaucoma. Use of psychotropic CNS meds having effect exceeding 14 days from screening. Planned use of prohibited drugs. Is pregnant or breast-feeding. Significant ECG or laboratory abnormalities. Experimental drug or medical device within 30 days prior to screening. Hypersensitivity to methylphenidate. Inability or unwillingness to comply with protocol. Well controlled on current ADHD treatment. Inability to take oral capsules.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label Phase Then 2-week Double Blind Phase (Placebo First, Then Methylphenidate HCl ER Capsule)<br>Open Label Phase: Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day. Double Blind Phase (2-weeks): Placebo: Capsule without active drug for 1 week Methylphenidate HCl ER Capsule: An optimized dose of Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week Dosed once daily in the morning | Drug: Methylphenidate Hydrochloride Extended Release Capsule<br>* An optimized dose of Methylphenidate Hydrochloride Extended Release Capsules 15, 20, 30 or 40 mg to be dosed once daily<br>* Other names: Biphentin®;Drug: Placebo<br>* Capsule without active drug<br>* Other names: Biphentin placebo;|
| Experimental: Open Label Phase Then 2-week Double Blind Phase (Methylphenidate HCl ER Capsule First, Then Placebo)<br>Open Label Phase: Subjects were dose optimized over a 2 to 4 week period. All subjects began at an initial Methylphenidate hydrochloride extended release capsules dose of 15 mg and were titrated weekly to an optimal dose using strengths of 15, 20, 30, up to the maximum of 40 mg/day. Double Blind Phase (2-weeks): Methylphenidate HCl ER Capsule: An optimized dose of Methylphenidate hydrochloride extended release capsules (15, 20, 30, or 40 mg) for 1 week Placebo: Capsule without active drug for 1 week Dosed once daily in the morning | Drug: Methylphenidate Hydrochloride Extended Release Capsule<br>* An optimized dose of Methylphenidate Hydrochloride Extended Release Capsules 15, 20, 30 or 40 mg to be dosed once daily<br>* Other names: Biphentin®;Drug: Placebo<br>* Capsule without active drug<br>* Other names: Biphentin placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Attention deficit, Hyperactivity, Impulsivity, Inattention