Study of Atomoxetine and OROS Methylphenidate to Treat Children and Adolescents Ages 6-17 With ADHD

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, effectiveness, and tolerability of atomoxetine and OROS methylphenidate, taken together, in the treatment of ADHD in children and adolescents ages 6-17.

Official Title
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Efficacy and Safety/Tolerability of OROS MPH (Concerta) Plus Atomoxetine (ATMX) in Children and Adolescents (Age 6-17) With Attention Deficit Hyperactivity Disorder (ADHD)

Conditions
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ADHD, Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Atomoxetine and OROS Methylphenidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female outpatients from 6 to 17 years old. Subjects with a DSM-IV diagnosis of ADHD by clinical interview, confirmed by the KSADS-E ADHD module. Subject with DSM-IV diagnosis of ADHD without previous treatment. Subjects with DSM-IV diagnosis of ADHD with a clinical history of a partial response to ATMX or methylphenidate as monotherapy. In phase I, subjects with a CGI-Severity of at least moderate impairment related to their ADHD (CGI >4). In phase II, subjects receiving therapeutic doses of ATMX with at least minor improvement in their clinical picture due to the ATMX as determined operationally (CGI-Improvement score indicating at least minor improvement relative to off-drug baseline) will be included. In phase II, only subjects receiving ATMX that also have evidence of persistent symptoms of ADHD and impairment related to their ADHD (a CGI-Severity of > minor impairment OR ADHD RS >18; AND GAF score <65) will have Concerta added to their regimen. Subjects' parents must provide informed consent and subjects' assent. Exclusion Criteria: Pregnant or nursing females or females not using proper contraception. Subjects with a medical condition or treatment that will either jeopardize subject safety or affect the scientific merit of the study. Subjects (or their families) who do not appear to be reliable reporters of their condition or who indicate they will not be able to meet the schedule of visits for the duration of the study. Subjects with Mental Retardation or Organic Brain Syndromes. Subjects who have a lifetime history of a psychotic or bipolar disorder. Subjects with recent or current (past 30 days) major depressive disorder or a clinically significant anxiety disorder that would potentially necessitate treatment during the trial. g. Subjects with recent evidence (past 30 days) of suicidality or homicidality will not be enrolled. Subjects with a recent history (e.g. three months) of a substance use disorder; or those with a positive urine for substances of abuse will not be enrolled. Subjects will be told that a positive urine for substances of abuse will be disclosed to their parents. Subjects taking stimulants or other psychotropics at the time of the evaluation. Subjects will not be discontinued from their current medication regimen (not including ATMX), unless authorized and supervised by their treating physician. Treatment of stimulants within one week of the evaluation; tricyclic antidepressants, bupropion, cholinesterase inhibitors, modafinil, clonidine/guanfacine, lithium/anticonvulsants for behavioral control, or serotonin reuptake inhibitors (except fluoxetine) for four weeks prior to entry are prohibited. Treatment with antipsychotics/neuroleptics and fluoxetine for 8 weeks prior to entry are prohibited. Subjects using any prescribed or over-the-counter concurrent treatment for ADHD. Subjects with a history of a lack of response to either ATMX or methylphenidate. Subjects with a history of a serious adverse event to either ATMX or methylphenidate.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Total treatment period is 7 weeks. Atomoxetine treatment will be initiated and maintained for 4 weeks. If the subject is a partial responder to atomoxetine treatment, OROS methylphenidate will then be added to his or her treatment regimen for the final 3 weeks of the study. | Drug: Atomoxetine and OROS Methylphenidate<br>* Subjects must have at least attempted to tolerate a dose of 1.2 mg/kg of atomoxetine. If tolerated, they must remain on this dose for at least two weeks. OROS methylphenidate will be target dosed and titrated to a maximum dose of 54 mg.<br>* Other names: Strattera, Concerta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attention Deficit Hyperactivity Disorder Rating Scale (ADHD RS) | The primary outcome was the ADHD rating scale. Change scores for the ADHD Rating Scale (RS), from baseline to endpoint (week 7 or last observation carried forward), were analyzed with paired t-tests and nonparametric Wilcoxon sign-rank tests. The best score is a score of 0 (no ADHD symptoms) and the worst score is the highest score possible (54). | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impressions - Level of Severity (CGIs) for ADHD and Other Psychiatric Disorders | Secondary analyses allowed us to evaluate the effects of treatment on additional measures of functioning (CGIs for ADHD and other psychiatric disorders). The CGI-Severity scale is as follows: 0 = Not assessed, 1 = normal, not at all ill, 2 = Borderline mentally ill, 3 = Mildly ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, 7 = Among the most extremely ill patients. | 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Attention Deficit Hyperactivity Disorder, Strattera, Concerta, Atomoxetine, OROS Methylphenidate