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

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 2009

Interventions

  • Drug: Atomoxetine
    • 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.
  • Drug: Placebo
    • 3 capsules of placebo have to be taken once daily in the morning, with or without food.

Arms, Groups and Cohorts

  • Experimental: Atomoxetine
    • 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.
  • Placebo Comparator: Placebo
    • Placebo matched to 1 week lead-in and 7 week standard target dose of atomoxetine

Clinical Trial Outcome Measures

Primary Measures

  • 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
    • Time Frame: Baseline, 8 weeks (W8)
    • 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.
  • 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
    • Time Frame: Baseline, 8 weeks
    • 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.
  • Change From Baseline cb CPT Variable: Impulsivity (Includes Commission Error [CE], Anticipatory Response [AR]) Q-scores At Week 8
    • Time Frame: Baseline, 8 weeks
    • 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.
  • Change From Baseline cb CPT Variable: Other (Includes Error Rate [ER] and Multi Response [MR]) Q-scores At Week 8
    • Time Frame: Baseline, 8 weeks
    • 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.

Secondary Measures

  • 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
    • Time Frame: Baseline, 8 weeks
    • 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.
  • Change From Baseline Clinical Global Impressions-Severity of ADHD (CGI-S-ADHD) Score at Week 8
    • Time Frame: Baseline, 8 weeks
    • 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).
  • Change From Baseline Weekly Rating Of Evening and Morning Behavior-Revised-Investigator Rated, Total and Subscores at Week 8
    • Time Frame: Baseline, 8 weeks
    • 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).

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 6 Years

Maximum Age: 12 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Eli Lilly and Company
  • Provider of Information About this Clinical Study
    • Chief Medical Officer, Eli Lilly
  • Overall Official(s)
    • Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon – Fri 9 AM – 5 PM Eastern time (UTC/GMT – 5 hours, EST), Study Director, Eli Lilly and Company

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.