Treatment of ADHD With Atomoxetine in Children & Adolescents With ADHD & Comorbid Dyslexia

• ClinicalTrials.gov Identifier: NCT00607919
• Recruitment Status: Completed
• First Posted: February 6, 2008
• Results First Posted: December 15, 2011
• Last Update Posted: December 15, 2011
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

This study will evaluate the effect of atomoxetine in treating Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in children and adolescents with ADHD and comorbid reading disability (dyslexia)

Condition or disease	Intervention/treatment	Phase
Attention Deficit Hyperactivity Disorder; Dyslexia	Drug: Atomoxetine; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 209 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind Placebo Controlled Study of Atomoxetine Hydrochloride for the Treatment of ADHD in Children and Adolescents With ADHD and Comorbid Dyslexia
• Study Start Date: March 2008
• Actual Primary Completion Date: November 2010
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Atomoxetine; Atomoxetine will be administered at 1.0 to 1.4 milligram/kilogram/day (mg/kg/day) given orally once daily in the morning. All eligible patients who complete the double-blind study period will have the option of participating in a 16-week open-label extension period in which patients will be treated with atomoxetine	Drug: Atomoxetine; Atomoxetine will be administered at 1.0 to 1.4 mg/kg/day given orally once daily in the morning for 16 to 32 weeks; Other Name: LY139603
Placebo Comparator: Placebo; Placebo will be packaged in the same way as experimental drug to enforce double-blind study design. Placebo will be administered orally once daily in the morning. All eligible patients who complete the double-blind study period will have the option of participating in a 16-week open-label extension period in which patients will be treated with atomoxetine.	Drug: Placebo; oral, daily, for 16 weeks

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total Score - Parent Version at Week 16 Endpoint [ Time Frame: Baseline, 16 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 (ADHD). Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Total scores range from 0-54. Least Square mean of change from baseline in ADHDRS is from a restricted maximum likelihood-based, mixed model repeated measures analysis which includes the effects of treatment, investigative site, baseline, visit, treatment-by-visit interaction, and baseline-by-visit interaction.

Secondary Outcome Measures :

1. Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Parent Version at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The ADHDRS-IV-Parent is an 18-item scale with 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD. Each item is scored on a 0 to 3 scale: 0=none (never or rarely); 1=mild (sometimes); 2=moderate (often); 3=severe (very often). Hyperactivity-impulsivity scores range 0-27, and inattention scores range 0-27. Total scores range from 0-54. Higher scores indicate higher impairment.
2. Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Teacher Version at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The ADHDRS-IV-Teacher is an 18-item scale with 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD. Each item is scored on a 0 to 3 scale: 0=none (never or rarely); 1=mild (sometimes); 2=moderate (often); 3=severe (very often). Hyperactivity-impulsivity scores range from 0-27, and inattention scores range from 0-27. Total scores range from 0-54. Higher scores indicate higher impairment.
3. Change From Baseline in Woodcock-Johnson III Scores at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The Woodcock Johnson Tests of Achievement has a Standard Battery (Tests 1-12) of a broad set of scores and an Extended Battery (Tests 13-22) on specific academic strengths and weaknesses. Tests associated with reading skills (1, 2, 7, 9, 13, 17, 20) were administered. Scores for each individual test can range from 0 to over 200 where anything 69 and below is very low and anything 131 and above is very superior. Higher scores indicate better reading skills.
4. Change From Baseline in Comprehensive Test of Phonological Processing (CTOPP) at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The CTOPP assesses phonological awareness, phonological memory, and rapid naming and is appropriate for ages 7 to 24. The test contains six core subtests. The composite scores are 1) Phonological Awareness, comprised of the standard scores of the Elision and Blending Words; 2) Phonological Memory, comprised of standard scores for Memory for Digits and Non-word Repetition; and 3) Rapid Naming, comprised of standard scores for Rapid Digit Naming and Rapid Letter Naming. Standard scores range from 1-20, and composite scores range from 35-165. Higher scores are better.
5. Change From Baseline in Gray Oral Reading Test-4 (GORT-4) at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The GORT-4 is a norm-referenced test of oral reading rate, accuracy, fluency, and comprehension valid for individuals aged 6 to 18 years old. The test has two parallel forms, Form A and Form B, that are administered in an alternating fashion (e.g. Week 0-Form A, Week 16-Form B, Week 32-Form A.) with each containing 14 separate stories and 5 multiple-choice comprehension questions for each story. GORT-4 yields the following scores: rate, accuracy, fluency, comprehension, and overall reading ability. Standard scores range from 1-20. Higher scores indicate better reading skills.
6. Change From Baseline in Test of Word Reading Efficiency (TOWRE) at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The TOWRE is a measure of an individual's ability to pronounce printed words accurately and fluently and is appropriate for individuals aged 6 to 24 years old. The TOWRE contains two subtests: Sight Word Efficiency (SWE) which assesses the number of real printed words that can be accurately identified within 45 seconds and Phonemic Decoding Efficiency (PDE) which measures the number of pronounceable printed non-words that can be accurately decoded within 45 seconds. Scores range from 45-146. Higher scores indicate higher reading proficiency.
7. Change From Baseline in Working Memory Test Battery for Children (WMTB-C) at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better) reflecting 3 main components of working memory: central executive (CE) control/regulation of working memory (Backward Digit Recall, Listening Recall, Counting Recall); phonological loop (PL) responsible for holding verbal information for short periods (Digit Recall, Word List Matching, Word List Recall, Non-word List Recall); and visuo-spatial sketchpad (VSSP) which holds information in visual and spatial form (Block Recall, Mazes Memory).
8. Change From Baseline in Life Participation Scale-child (LPS-C) Score at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   LPS-C is a short (24 item, 0-3 points per item) parent-rated scale that is designed to assess changes in adaptive functioning related to treatment for ADHD. This scale measures improvements in social, emotional, cognitive, educational, and affiliative (family, friends) functioning, which indirectly reflect improvements in executive functioning. Happy/social subscores range from 0-18, and self-control subscores range from 0-54. Total scores range from 0-72. Higher scores are better for LPS.
9. Change From Baseline in Kiddie Sluggish Cognitive Tempo (K-SCT) at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
   The K-SCT rating scale contains 3 components: Youth, Parent, and Teacher ratings. It queries 17 candidate SCT symptoms, such as daydreams, lost in a fog, sluggish/drowsy. Scores range from 0-51. Lower scores indicate less sluggish.
10. Change From Baseline in Multidimensional Self Concept Scale (MSCS) at Week 16 Endpoint [ Time Frame: Baseline, 16 weeks ]
    The MSCS is an overall assessment of self concept or an individual measure of any of the six scaled dimensions of self concept: Social, Competence, Affect, Academic, Family, and Physical. Standard scores range from 45-145. Higher scores are better (indicate higher self concept).
11. Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Parent Version at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The ADHDRS-IV-parent is an 18-item scale with 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD. Each item is scored on a 0 to 3 scale: 0=none (never or rarely); 1=mild (sometimes); 2=moderate (often); 3 =severe (very often). Hyperactivity-impulsivity scores range from 0-27, and inattention scores range from 0-27. Total scores range from 0-54. Higher scores indicate higher impairment.
12. Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Teacher Version at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The ADHDRS-IV-Teacher is an 18-item scale with 1 item for each of the 18 symptoms contained in the DSM-IV diagnosis of ADHD. Each item is scored on a 0 to 3 scale: 0=none (never or rarely); 1=mild (sometimes); 2=moderate (often); 3 =severe (very often). Hyperactivity-impulsivity scores range from 0-27, and inattention scores range from 0-27. Total scores range from 0-54. Higher scores indicate higher impairment.
13. Change From Baseline in Woodcock-Johnson III Scores at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The Woodcock Johnson Tests of Achievement has a Standard Battery (Tests 1-12) of a broad set of scores and an Extended Battery (Tests 13-22) on specific academic strengths and weaknesses. Tests associated with reading skills (1, 2, 7, 9, 13, 17, 20) were administered. Scores for each individual test can range from 0 to over 200 where anything 69 and below is very low and anything 131 and above is very superior. Higher scores indicate better reading skills.
14. Change From Baseline in Comprehensive Test of Phonological Processing (CTOPP) at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The CTOPP assesses phonological awareness, phonological memory, and rapid naming and is appropriate for ages 7 to 24. The test contains six core subtests. The composite scores are 1) Phonological Awareness, comprised of the standard scores of the Elision and Blending Words; 2) Phonological Memory, comprised of standard scores for Memory for Digits and Non-word Repetition; and 3) Rapid Naming, comprised of standard scores for Rapid Digit Naming and Rapid Letter Naming. Standard scores range from 1-20, and composite scores range from 35-165. Higher scores are better.
15. Change From Baseline in Gray Oral Reading Test-4 (GORT-4) at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The GORT-4 is a norm-referenced test of oral reading rate, accuracy, fluency, and comprehension valid for individuals aged 6 to 18 years old. The test has two parallel forms, Form A and Form B, that are administered in an alternating fashion (e.g. Week 0-Form A, Week 16-Form B, Week 32-Form A.) with each containing 14 separate stories and 5 multiple-choice comprehension questions for each story. GORT-4 yields the following scores: rate, accuracy, fluency, comprehension, and overall reading ability. Standard scores range from 1-20. Higher scores indicate better reading skills.
16. Change From Baseline in Test of Word Reading Efficiency (TOWRE) at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The TOWRE is a measure of an individual's ability to pronounce printed words accurately and fluently and is appropriate for individuals aged 6 to 24 years old. The TOWRE contains two subtests: Sight Word Efficiency (SWE) which assesses the number of real printed words that can be accurately identified within 45 seconds and Phonemic Decoding Efficiency (PDE) which measures the number of pronounceable printed non-words that can be accurately decoded within 45 seconds. Scores range from 45-146. Higher scores indicate higher reading proficiency.
17. Change From Baseline in Working Memory Test Battery for Children (WMTB-C) at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    WMTB-C is assessment of working memory capacities, consisting of 9 subtests (Trials Correct Scores [Range from 55-145], Higher scores are better) reflecting 3 main components of working memory: central executive (CE) control/regulation of working memory (Backward Digit Recall, Listening Recall, Counting Recall); phonological loop (PL) responsible for holding verbal information for short periods (Digit Recall, Word List Matching, Word List Recall, Non-word List Recall); and visuo-spatial sketchpad (VSSP) which holds information in visual and spatial form (Block Recall, Mazes Memory).
18. Change From Baseline in Life Participation Scale-child (LPS-C) Score at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    LPS-C is a short (24 item, 0-3 points per item) parent-rated scale that is designed to assess changes in adaptive functioning related to treatment for ADHD. This scale measures improvements in social, emotional, cognitive, educational, and affiliative (family, friends) functioning, which indirectly reflect improvements in executive functioning. Happy/social subscores range from 0-18, and self-control subscores range from 0-54. Total scores range from 0-72. Higher scores are better for LPS.
19. Change From Baseline in Kiddie Sluggish Cognitive Tempo (K-SCT) at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The K-SCT rating scale contains 3 components: Youth, Parent, and Teacher ratings. It queries 17 candidate SCT symptoms, such as daydreams, lost in a fog, sluggish/drowsy. Scores range from 0-51. Lower scores indicate less sluggish.
20. Change From Baseline in Multidimensional Self Concept Scale (MSCS) at Week 32 Endpoint [ Time Frame: Baseline, 32 weeks ]
    The MSCS is an overall assessment of self concept or an individual measure of any of the six scaled dimensions of self concept: Social, Competence, Affect, Academic, Family, and Physical. Standard scores range from 45-145. Higher scores are better (indicate higher self concept).

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• patients must meet Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for Attention-Deficit/Hyperactivity Disorder (ADHD)
• patients must achieve a score of 80 or more on the Full Scale Intelligence Quotient
• child or adolescent patients must be 10 to 16 years old
• must be able to communicate in English
• must be able to swallow capsules
• be reliable to keep appointments for clinic visits and all related tests

Exclusion Criteria:

• patients who weigh less than 25 Kg or greater than 70 Kg
• patients with a history of alcohol or drug abuse on a repeated basis within the past 3 months
• patients with documented history of autism, Asperger's syndrome or pervasive developmental disorder
• females who are pregnant or breastfeeding
• patients with a history of severe allergy to more than one class of medications
• patients with documented history of bipolar I or bipolar II disorder, or psychosis

Contacts and Locations

Locations

United States, California

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.

Irvine, California, United States, 92612

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.

Palo Alto, California, United States, 94306

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.

San Francisco, California, United States, 94143

United States, Connecticut

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.

New Haven, Connecticut, United States, 06511

United States, Florida

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.

Tampa, Florida, United States, 33607

United States, Illinois

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.

Libertyville, Illinois, United States, 60048

United States, Indiana

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.

Indianapolis, Indiana, United States, 46202

United States, Kentucky

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.

Lexington, Kentucky, United States, 40509

United States, North Carolina

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.

Chapel Hill, North Carolina, United States, 27517

United States, Ohio

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.

Cincinnati, Ohio, United States, 45206

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.

Columbus, Ohio, United States, 43210

United States, Oklahoma

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.

Oklahoma City, Oklahoma, United States, 73117

United States, Pennsylvania

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.

Pittsburgh, Pennsylvania, United States, 15241

United States, Texas

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.

San Antonio, Texas, United States, 78229

United States, Vermont

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.

Burlington, Vermont, United States, 05401

United States, Washington

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.

Spokane, Washington, United States, 99202

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: 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); Eli Lilly and Company

More Information

Additional Information:

(Lilly Clinical Trial Registry) 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

McBurnett K, Clemow D, Williams D, Villodas M, Wietecha L, Barkley R. Atomoxetine-Related Change in Sluggish Cognitive Tempo Is Partially Independent of Change in Attention-Deficit/Hyperactivity Disorder Inattentive Symptoms. J Child Adolesc Psychopharmacol. 2017 Feb;27(1):38-42. doi: 10.1089/cap.2016.0115. Epub 2016 Nov 15.

Shaywitz S, Shaywitz B, Wietecha L, Wigal S, McBurnett K, Williams D, Kronenberger WG, Hooper SR. Effect of Atomoxetine Treatment on Reading and Phonological Skills in Children with Dyslexia or Attention-Deficit/Hyperactivity Disorder and Comorbid Dyslexia in a Randomized, Placebo-Controlled Trial. J Child Adolesc Psychopharmacol. 2017 Feb;27(1):19-28. doi: 10.1089/cap.2015.0189. Epub 2016 Jul 13.

Bangs ME, Wietecha LA, Wang S, Buchanan AS, Kelsey DK. Meta-analysis of suicide-related behavior or ideation in child, adolescent, and adult patients treated with atomoxetine. J Child Adolesc Psychopharmacol. 2014 Oct;24(8):426-34. doi: 10.1089/cap.2014.0005. Epub 2014 Jul 14.

Wietecha L, Williams D, Shaywitz S, Shaywitz B, Hooper SR, Wigal SB, Dunn D, McBurnett K. Atomoxetine improved attention in children and adolescents with attention-deficit/hyperactivity disorder and dyslexia in a 16 week, acute, randomized, double-blind trial. J Child Adolesc Psychopharmacol. 2013 Nov;23(9):605-13. doi: 10.1089/cap.2013.0054. Epub 2013 Nov 9.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00607919
• Other Study ID Numbers: 11672; B4Z-US-LYEB ( Other Identifier: Eli Lilly and Company )
• First Posted: February 6, 2008
• Results First Posted: December 15, 2011
• Last Update Posted: December 15, 2011
• Last Verified: November 2011

Additional relevant MeSH terms:

Dyslexia; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Learning Disorders; Atomoxetine Hydrochloride; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Adrenergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs