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

Study Overview
=================
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)

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

Conditions
-----------------
Attention Deficit Hyperactivity Disorder, Dyslexia

Intervention / Treatment
-----------------
* Drug: Atomoxetine
* Drug: Placebo


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atomoxetine<br>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<br>* 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<br>* Other names: LY139603;|
| Placebo Comparator: Placebo<br>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<br>* oral, daily, for 16 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total Score - Parent Version at Week 16 Endpoint | 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. | Baseline, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Parent Version at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Teacher Version at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Woodcock-Johnson III Scores at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Comprehensive Test of Phonological Processing (CTOPP) at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Gray Oral Reading Test-4 (GORT-4) at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Test of Word Reading Efficiency (TOWRE) at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Working Memory Test Battery for Children (WMTB-C) at Week 16 Endpoint | 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). | Baseline, 16 weeks | 
| Change From Baseline in Life Participation Scale-child (LPS-C) Score at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Kiddie Sluggish Cognitive Tempo (K-SCT) at Week 16 Endpoint | 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. | Baseline, 16 weeks | 
| Change From Baseline in Multidimensional Self Concept Scale (MSCS) at Week 16 Endpoint | 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). | Baseline, 16 weeks | 
| Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Parent Version at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHDRS) Total and Subscores - Teacher Version at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Woodcock-Johnson III Scores at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Comprehensive Test of Phonological Processing (CTOPP) at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Gray Oral Reading Test-4 (GORT-4) at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Test of Word Reading Efficiency (TOWRE) at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Working Memory Test Battery for Children (WMTB-C) at Week 32 Endpoint | 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). | Baseline, 32 weeks | 
| Change From Baseline in Life Participation Scale-child (LPS-C) Score at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Kiddie Sluggish Cognitive Tempo (K-SCT) at Week 32 Endpoint | 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. | Baseline, 32 weeks | 
| Change From Baseline in Multidimensional Self Concept Scale (MSCS) at Week 32 Endpoint | 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). | Baseline, 32 weeks |