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

Eli Lilly and Company125 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

125

Conditions

Attention Deficit Hyperactivity Disorder

Interventions

Eligibility

Sex: ALLMin age: 6 YearsMax age: 12 Years

Medical Language ↔ Plain English

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

Locations (16)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Berlin, Germany

Cologne, Germany

Datteln, Germany

Dorsten, Germany

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, 8 weeks

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: Baseline, 8 weeks

Düsseldorf, Germany

Eberswalde, Germany

Freiburg im Breisgau, Germany

Fulda, Germany

Giessen, Germany

Hagen, Germany