Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD) - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00191906

Purpose

To test the hypothesis that a 4 week treatment with atomoxetine is more effective than placebo in patients with combined type Attention Deficit/Hyperactivity Disorder (ADHD), patients with only Reading Disorder, and patients with combined type ADHD and Reading Disorder.

Condition	Intervention	Phase
Attention Deficit Hyperactivity Disorder Reading Disorder	Drug: Atomoxetine Hydrochloride Drug: placebo	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Crossover Comparison of Atomoxetine and Placebo in Child Outpatients With Attention-Deficit/Hyperactivity Disorder, Reading Disorder, or Comorbid Attention-Deficit/Hyperactivity Disorder and Reading Disorder.

Resource links provided by NLM:

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder

Drug Information available for: Atomoxetine hydrochloride Atomoxetine

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Stop Signal Reaction Time (SSRT) as Derived From the Stop Signal Reaction Time Paradigm [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal.

Secondary Outcome Measures:

Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset [ Time Frame: Baseline and 4 weeks of therapy ] [ Designated as safety issue: No ]
SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal.
Change From Baseline in Mean Stop Signal Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset [ Time Frame: Baseline and 4 weeks of therapy ] [ Designated as safety issue: No ]
SSRT measures response execution (go trials) and response inhibition (stop trials). Go trials consist of stimulus (airplane). Child to press response button corresponding to direction airplane is pointing. Stop trials consist of go trial and audible stop signal. Initial delay between go trial and stop signal = 250 msec. If child succeeded in inhibiting response, delay on next stop trial increased by 50 msec, otherwise, delay decreased by 50 msec. SSRT = subtract mean delay from mean go signal reaction time. Lower scores mean better ability to suppress response when presented with stop signal.
Lexical Decision Task Mean Reaction Time: Correct Words [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measure of reaction time to identify whether a word displayed on a computer is a real or correct word versus a pseudo word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying correct words correctly.
Lexical Decision Task Mean Reaction Time: Pseudo Words [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measure of reaction time to identify whether a word displayed on a computer is a pseudo word versus a real or correct word. During the performance of the lexical decision task that was presented on a computer, the reaction times and accuracy of responses were measured. Data presented are the mean reaction times over the 4 weeks of each therapy for identifying pseudo words correctly.
Working Memory by Corsi Block Tapping Test (CBTT) [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measures the visuo-spatial working memory span, and corresponds to the longest sequence of blocks that has been reproduced correctly at least once. Scores can range from 3 to 8, with the higher score indicating better function.
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total Score [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is the sum of the scores on the 18 items and range from 0 to 54.
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Inattention Subscale [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measures the degree of inattention symptoms based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), for a total Inattention Subscale score range of 0 to 27.
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Hyperactivity-Impulsivity Subscale [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measures the degree of hyperactivity-impulsivity symptoms, based on answers to 9 items. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often) for a total Hyperactivity-Impulsivity Subscale score of 0 to 27.
Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored - Total T-Score [ Time Frame: Baseline and Week 4 of initial therapy and Week 4 of crossover therapy ] [ Designated as safety issue: No ]
Measures the 18 symptoms contained in the DSM-IV diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total score is computed as the sum of the scores on each of the 18 items. Total score is the sum of the scores on the 18 items and range from 0 to 54. Total T-score = (Total Score - 50)/10. Total T-score ranges from -5 (low severity) to 0.4 (high severity).
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Improvement Scale [ Time Frame: 4 week therapy endpoint ] [ Designated as safety issue: No ]
Measures total improvement (or worsening) of a patient's ADHD symptoms from the beginning of treatment (1=very much improved, 7=very much worsened).
Clinical Global Impression-Attention Deficit Hyperactivity Disorder-Severity Scale [ Time Frame: 4 week therapy endpoint ] [ Designated as safety issue: No ]
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 in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudohomophones [ Time Frame: Baseline and 4 weeks of therapy ] [ Designated as safety issue: No ]
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudohomophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly.
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C to Normal Control Group in >=10 Year Old Subset: Pseudo Words [ Time Frame: Baseline and 4 weeks of therapy ] [ Designated as safety issue: No ]
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying pseudo words correctly.
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudohomophones [ Time Frame: Baseline and 4 weeks of therapy ] [ Designated as safety issue: No ]
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to identifying psuedohomophones correctly.
Change From Baseline in Phonological Task Mean Reaction Time Comparison of ADHD-C+RD and RD to Reading Disordered Control Group in >=10 Year Old Subset: Pseudo Words [ Time Frame: Baseline and 4 weeks of therapy ] [ Designated as safety issue: No ]
Measure of reaction time in determining whether the stimulus sounds like a real word ('yes' response) or not ('no' response) using pseudo homophones and pseudo words. Data presented here are for reaction time to indentifying pseudo words correctly.

Enrollment:	121
Study Start Date:	April 2005
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Atomoxetine first, then Placebo Atomoxetine, 1.2 mg/kg/day, by mouth (PO) for 4 weeks, 2 week washout period and cross-over to placebo, every day (QD), PO for 4 weeks	Drug: Atomoxetine Hydrochloride Atomoxetine, 1.2 mg/kg/day, by mouth (PO) Other Names: LY139603 Strattera Drug: placebo Placebo, every day (QD), by mouth (PO)
Experimental: Placebo first, then Atomoxetine Placebo, every day (QD), by mouth (PO) for 4 weeks, 2 week washout period and cross-over to atomoxetine 1.2 mg/kg/day, PO for 4 weeks	Drug: Atomoxetine Hydrochloride Atomoxetine, 1.2 mg/kg/day, by mouth (PO) Other Names: LY139603 Strattera Drug: placebo Placebo, every day (QD), by mouth (PO)
No Intervention: Normal Control Normal controls were children selected from the general population. The normal control was matched (have same proportion) by sex (male/female) and by age (have same age range) as the study population.
No Intervention: Reading Disordered Control The reading disordered control group is comprised of children with reading disorder who receive standard remedial teaching therapy.

Ages Eligible for Study:	8 Years to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Belgium
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.
Gent, Belgium, 9000
Netherlands
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.
Almere, Netherlands, 1311 RL
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.
Amsterdam, Netherlands, 1081 BT
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.
Breda, Netherlands, 4819 EV
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.
Vught, Netherlands, 5260 GB

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT00191906 History of Changes
Other Study ID Numbers:	7955, B4Z-MC-LYCK
Study First Received:	September 12, 2005
Results First Received:	December 11, 2008
Last Updated:	May 17, 2010
Health Authority:	Belgium: Directorate general for the protection of Public health: Medicines; Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)