Comparison of Atomoxetine Versus Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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This is a two-arm, parallel, randomized, double-blind, placebo-controlled Phase 4 multicenter trial to compare the whole day efficacy of atomoxetine versus placebo in children aged 6 through 12 years with Attention-Deficit/Hyperactivity Disorder (ADHD) treated in an inpatient, day-patient and outpatient setting in Germany. Core symptoms will be measured during once or bi-weekly visits, three times per visit-day, by a computer based Continuous Performance Test. Following an initial 3-28-day screening and washout phase, patients will be assigned to double-blind treatment with atomoxetine or placebo. In the verum arm, a one-week atomoxetine treatment period with the 0.5 mg/kg per day lead-in dose will be succeeded by a 7 week period at the target dose of 1.2 mg/kg per day.

Official Title
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A Randomized, Double Blind Comparison of the Effects of Atomoxetine Versus Placebo on Neuropsychological Outcomes Across the Day in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) by Use of a Computer Based Continuous Performance Test (cb CPT)

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Atomoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients who are at least 6 years of age, and who will not have reached their 13th birthday Diagnosis of ADHD Normal intelligence Able to swallow capsules Exclusion Criteria: Weight less than 20 kg or more than 60 kg at study entry Prior treatment with atomoxetine History of seizure disorder, suicidal risk, alcohol or drug abuse within the past 3 months History of severe allergies or multiple adverse drug reactions Cardiovascular disorders: hypertension, unexplained cardiac signs or symptoms, QT prolongation, inherited cardiac disorders

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br>0.5 milligram per kilogram (mg/kg) per day lead-in dose for 1 weeks followed by 7 weeks at 1.2 mg/kg per day dose. | Drug: Atomoxetine<br>* A one-week atomoxetine treatment period with the 0.5 mg/kg per day lead-in dose will be succeeded by a 7 week period at the target dose of 1.2 mg/kg per day. 3 capsules of study medication have to be taken once daily in the morning, with or without food.<br>* Other names: LY139603;|
| Placebo Comparator: Placebo<br>Placebo matched to 1 week lead-in and 7 week standard target dose of atomoxetine | Drug: Placebo<br>* 3 capsules of placebo have to be taken once daily in the morning, with or without food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Computer-based Continuous Performance Test (cb- CPT; Qbtech AB, Sweden), Variable: Hyperactivity (Includes Time Active [TA], Distance [DIS], Area [AR], Microevents [ME], Motion Simplicity [MS]) Q-scores At Week 8 | Infra-red camera tracks movement of head reflector on patient performing computer test. Hyperactivity test variables: TA=percent time patient moved>1 centimeter (cm)/second; DIS=path of movement (m); AR=total area (cm2) of movements; ME=number of position changes>1 mm; MS=degree (percent) of directional changes. Results are converted to Q-scores (age and sex-adjusted normalized scores with a mean=0 and standard deviation (SD)=1 in general population, expressing the probability determined by the Gamma function in terms of SD of Gaussian density). Higher scores reflect more severe symptoms. | Baseline, 8 weeks (W8) | 
| Change From Baseline cb CPT Variable: Inattention (Includes Reaction Time Variation[RTV], Omission Error [OR], Mean Reaction Time [mRT], Normalized Variation Of Reaction Time [nVRT]) Q-scores At Week 8 | Computer test. Patient is to press button if target appears, but not at non-target. Inattention test variables: mRT=average time (ms) from target presentation to response; RTV=standard deviation of mRT; nVRT=RTV expressed in terms of RT (variation as a percent of mean value); OE= percent of omitted targets. Results are converted to Q-scores (age and sex-adjusted normalized scores with a mean=0 and SD=1 in the general population, expressing the probability determined by the Gamma function in terms of SD of Gaussian density). Higher scores reflect more severe symptoms. | Baseline, 8 weeks | 
| Change From Baseline cb CPT Variable: Impulsivity (Includes Commission Error [CE], Anticipatory Response [AR]) Q-scores At Week 8 | Computer test. Patient is to press button if target appears, but not at non-target. Impulsivity variables during test: CE=percent of response to non-target; ANT=percent of responses prior to target presentation. Results are converted to Q-scores (age and sex-adjusted normalized scores with a mean=0 and standard deviation=1 in the general population, expressing the probability determined by the Gamma function in terms of standard deviation of Gaussian density). Higher scores reflect more severe symptoms. | Baseline, 8 weeks | 
| Change From Baseline cb CPT Variable: Other (Includes Error Rate [ER] and Multi Response [MR]) Q-scores At Week 8 | Computer test. Patient is to press button if target appears, but not at non-target. Other variables during test: ER=percent of overall incorrect responses (CE and OE); MR=percent of multiple responses per presentation of target (patient responds more than once to target). Results are converted to Q-scores (age and sex-adjusted normalized scores with a mean=0 and standard deviation=1 in the general population, expressing the probability determined by the Gamma function in terms of standard deviation of Gaussian density). Higher scores reflect more severe symptoms. | Baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered And Scored (ADHDRS-IV-Parent:Inv) Total Score At Week 8 | Measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0 to 54. | Baseline, 8 weeks | 
| Change From Baseline Clinical Global Impressions-Severity of ADHD (CGI-S-ADHD) Score at Week 8 | CGI-S-ADHD measures severity of the patient's overall severity of ADHD symptoms (1=normal, not at all ill; 7=among the most extremely ill patients). | Baseline, 8 weeks | 
| Change From Baseline Weekly Rating Of Evening and Morning Behavior-Revised-Investigator Rated, Total and Subscores at Week 8 | Weekly Rating Of Evening & Morning Behavior-Revised-Investigator Rated (WREMB-R-Inv) measures the level of difficulty of 11 common morning or evening behaviors (e.g. getting out of bed, doing homework, sitting through dinner). Possible scores for each item range from 0 (no difficulty) to 3 (a lot of difficulty) with a Total score (maximum score=33), Morning subscore (maximum score=9), Evening subscore (maximum score=24), and Item 11 score which pertains to degree of difficulty falling asleep (maximum score=3). | Baseline, 8 weeks |