A Comparative Effectiveness Study Evaluating OROS Methylphenidate HCl, Ritalin (Methylphenidate HCl), and Placebo for the Treatment of Attention Deficit Hyperactivity Disorder in Children

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness (onset of effect, time to loss of effect, and overall efficacy) of methylphenidate given as an OROSÂ® (methylphenidate HCl) formulation, compared to immediate-release RitalinÂ® and placebo for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children using standardized attention and behavior scales, and other assessments. Both OROSÂ® Methylphenidate HCl and RitalinÂ® contain the central nervous system stimulant, methylphenidate HCl.

Detailed Description
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Attention Deficit Hyperactivity Disorder (ADHD) represents the most common neurobehavioral disorder in children, affecting 3% to 5% of the school-age population. This is a double-blind, double-dummy, randomized, placebo-controlled, active-controlled, crossover trial in children with ADHD, to compare the safety and effectiveness (onset of effect, time to loss of effect and overall efficacy) of OROS® Methylphenidate HCl with standard immediate-release Ritalin® and placebo. During this study, patients receive each of the three treatments (OROS® Methylphenidate HCl 18, 36 or 54 milligrams per day, Ritalin® 5, 10 or 15 milligrams three times per day, or placebo) for 7 days, and are assigned to one of three dosage levels depending upon their prestudy methylphenidate dose and regimen. The total study participation for each patient will be 21 days. Since ADHD is manifested in a variety of settings and can affect attention and behavior, this study assesses efficacy in home, community school, and laboratory school settings using numerous assessments designed to evaluate various aspects of the disorder. These assessments are completed by a variety of raters, including the parents/caregivers, community school teachers, laboratory school teachers and the laboratory school counselor. The primary measure of effectiveness is the community school teacher's rating on the IOWA Conners Inattention/Overactivity subscale. Additional measures of effectiveness include IOWA Conners (Inattention/Overactivity and Oppositional/Defiance subscale) ratings, SKAMP attention and deportment ratings, peer interaction and other behavioral ratings, global assessments, accuracy and productivity of independent assigned academic seatwork, and assessments of positive and negative social behaviors, classroom rule violations and disruptive behaviors. Safety evaluations include the incidence of adverse events, vital signs, sleep quality, appetite, and the presence/severity of tics (hard-to-control, repeated twitching of any parts of the body or hard-to-control repeating of sounds or words). Patients will be given oral doses of: OROS® (methylphenidate HCl) either 1, 2 or 3 of the 18 milligram tablets once daily, Ritalin® 5, 10, or 15 mg (encapsulated/single capsule) three times per day, or placebo. There are three treatment groups, each group dosing for 7 days for a total of 21 days on study.

Official Title
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Comparative Crossover Study of OROS (Methylphenidate HCl), Ritalin, and Placebo in Children With ADHD

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Ritalin
* Drug: OROS Methylphenidate HCl
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of one of the three subtypes of Attention Deficit Hyperactivity Disorder (ADHD) verified by both a parent/child interview and a teacher assessment using SNAP-IV questionnaires taking 5 - 20 mg of immediate-release methylphenidate (Ritalin®) at least twice a day, 20 - 60 mg of sustained-release methylphenidate (Ritalin-SR®) per day, or a combination of immediate-release and sustained-release methylphenidate up to a daily dose not exceeding 60 mg having used methylphenidate for at least 3 months at some time in the past and have been on the same dose for the previous 4-week period without any significant adverse experiences, considered to be positive responders to methylphenidate therapy, and agreeing to take only the supplied study drug as treatment for ADHD during the three-week treatment phase of the study able to comply with the study visit schedule and whose parent(s) and teacher are willing and able to complete the protocol-specified assessments, including behavior modification procedures agreeing not to ingest any caffeine containing beverages (e.g., coffee or soda) or foods (e.g., chocolate) on days 7, 14, and 21 of the study Exclusion Criteria: Patients having clinically significant gastrointestinal problems, including narrowing of the gastrointestinal tract considered markedly anxious, tense, agitated, or depressed, having psychotic disorders, a history of seizures, or having a diagnosis of Tourette's syndrome whose primary treatment focus is oppositional-defiant disorder, conduct disorder, or tics, or whose primary treatment focus is other psychiatric conditions such as depressive disorders, bipolar disorders, or other mood disorders having a mean of two blood pressure measurements (systolic or diastolic) equal to or greater than the 95th percentile for age, sex, and height if female, have begun menstruation

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>OROS Methylphenidate HCl | Drug: OROS Methylphenidate HCl<br> <br> |
| Active Comparator: 002<br>Ritalin | Drug: Ritalin<br> <br> |
| Placebo Comparator: 003<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IOWA Conners Inattention/Overactivity subscale ratings by the Community School Teacher on Days 6, 13 and 20, evaluating study days 2 - 6, 9 - 13, and 16 - 20, respectively. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IOWA Conners Inattention/Overactivity and Oppositional/Defiance subscale ratings; SKAMP attention and deportment ratings; Global assessments; Accuracy and completion on assigned academic tasks; Peer interactions ratings; Incidence of adverse events |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Attention Deficit Hyperactivity Disorder, OROS®, Ritalin®, children, methylphenidate